[Paragraph-level] PMCID: PMC2910708 Section: RESULTS PassageIndex: 16

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: c.1735_1737delGAT | Summary: The deletion mutation c.1735_1737delGAT in KIT exon 11 is associated with tumor development or progression. Evidence Type: Oncogenic | Mutation: c.1661_1705del45bp | Summary: The deletion mutation c.1661_1705del45bp in KIT exon 11 is associated with tumor development or progression. Evidence Type: Functional | Mutation: c.1728_1766dup39bp | Summary: The duplication mutation c.1728_1766dup39bp in KIT exon 11 alters molecular or biochemical function.

Gene→Variant (gene-first): 3815:L588dup 3815:Y568del 3815:c.1661_1705del45bp 3815:c.1728_1766dup39bp 3815:c.1735_1737delGAT 3815:p.D579del

Genes: 3815

Variants: L588dup Y568del c.1661_1705del45bp c.1728_1766dup39bp c.1735_1737delGAT p.D579del

[Paragraph-level] PMCID: PMC2910708 Section: RESULTS PassageIndex: 5

Evidence Type(s): None

Summary: Not enough information in this passage.

Gene→Variant (gene-first): 5156:D842V

Genes: 5156

Variants: D842V

[Paragraph-level] PMCID: PMC2910708 Section: RESULTS PassageIndex: 4

Evidence Type(s): None

Summary: Not enough information in this passage.

Gene→Variant (gene-first): 5156:p.R822 H

Genes: 5156

Variants: p.R822 H

[Paragraph-level] PMCID: PMC4398541 Section: RESULTS PassageIndex: 12

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: L23F | Summary: The L23F mutation displays compromised/partial PIP3 catalytic activity in yeast, indicating an alteration in molecular function. Evidence Type: Functional | Mutation: N31A | Summary: The N31A mutation did not affect PIP3 catalytic activity in yeast but impaired the nuclear accumulation of PTEN 1-375 in mammalian cells, suggesting a change in molecular function.

Gene→Variant (gene-first): 5728:L23F 5728:N31A

Genes: 5728

Variants: L23F N31A

[Paragraph-level] PMCID: PMC4398541 Section: RESULTS PassageIndex: 10

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: K13R | Summary: The K13R mutation alters the nuclear localization of PTEN and enhances its ability to counteract PI3K activity in a yeast model. Evidence Type: Functional | Mutation: R14K | Summary: The R14K mutation affects the nuclear localization of PTEN and maintains its phosphatase activity in vivo. Evidence Type: Functional | Mutation: K13E | Summary: The K13E mutation results in a total loss of phosphatase activity in vivo. Evidence Type: Functional | Mutation: R15K | Summary: The R15K mutation increases the nuclear accumulation of PTEN but does not display phosphatase activity in vivo. Evidence Type: Functional | Mutation: K13A | Summary: The K13A mutation is part of a combined mutation that affects nuclear localization, indicating a role in PTEN's functional activity. Evidence Type: Functional | Mutation: R14A | Summary: The R14A mutation is part of a combined mutation that affects nuclear localization, indicating a role in PTEN's functional activity. Evidence Type: Functional | Mutation: R15A | Summary: The R15A mutation is part of a combined mutation that affects nuclear localization, indicating a role in PTEN's functional activity.

Gene→Variant (gene-first): 100329167:Arg14 5728:Arg15 5728:K13A 5728:K13E 5728:K13R 5728:Lys13 100329167:R14A 100329167:R14K 5728:R15A 5728:R15K

Genes: 100329167 5728

Variants: Arg14 Arg15 K13A K13E K13R Lys13 R14A R14K R15A R15K

[Paragraph-level] PMCID: PMC4398541 Section: RESULTS PassageIndex: 8

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: R15A | Summary: The R15A mutation resulted in a complete loss-of-function of PTEN's PIP3 phosphatase activity, indicating an alteration in molecular function. Evidence Type: Functional | Mutation: Y16A | Summary: The Y16A mutation displayed a complete loss-of-function in PTEN's PIP3 phosphatase activity, suggesting it alters molecular function. Evidence Type: Functional | Mutation: D24A | Summary: The D24A mutation led to a complete loss-of-function of PTEN's PIP3 phosphatase activity, indicating a change in biochemical function. Evidence Type: Functional | Mutation: I32A | Summary: The I32A mutation resulted in a complete loss-of-function of PTEN's PIP3 phosphatase activity, reflecting an alteration in molecular function. Evidence Type: Functional | Mutation: M35A | Summary: The M35A mutation caused a complete loss-of-function of PTEN's PIP3 phosphatase activity, indicating a change in biochemical function. Evidence Type: Functional | Mutation: A39V | Summary: The A39V mutation resulted in a complete loss-of-function of PTEN's PIP3 phosphatase activity, suggesting it alters molecular function. Evidence Type: Functional | Mutation: I33A | Summary: The I33A mutation partially compromised PTEN activity, indicating an alteration in molecular function. Evidence Type: Functional | Mutation: L42A | Summary: The L42A mutation abrogated both nuclear accumulation and PIP3 phosphatase activity of PTEN, indicating a change in molecular function.

Gene→Variant (gene-first): 5728:A39V 5728:D24A 5728:I32A 5728:I33A 5728:I5A 5728:K6A 5728:L42A 5728:M35A 5728:P38A 5728:Q17A 5728:R15A 5728:S10A 5728:Y16A

Genes: 5728

Variants: A39V D24A I32A I33A I5A K6A L42A M35A P38A Q17A R15A S10A Y16A

[Paragraph-level] PMCID: PMC4398541 Section: RESULTS PassageIndex: 7

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: A39V | Summary: The A39V mutation alters the nuclear accumulation of PTEN, indicating a change in its molecular function related to localization. Evidence Type: Functional | Mutation: D19A | Summary: The D19A mutation affects the cytoplasmic localization of PTEN, suggesting an alteration in its molecular function. Evidence Type: Functional | Mutation: G20A | Summary: The G20A mutation influences the cytoplasmic localization of PTEN, indicating a change in its molecular function. Evidence Type: Functional | Mutation: F21A | Summary: The F21A mutation impacts the cytoplasmic localization of PTEN, suggesting an alteration in its molecular function. Evidence Type: Functional | Mutation: K13A | Summary: The K13A mutation inhibits nuclear entry of PTEN, indicating a change in its molecular function related to localization. Evidence Type: Functional | Mutation: R14A | Summary: The R14A mutation inhibits nuclear entry of PTEN, suggesting an alteration in its molecular function. Evidence Type: Functional | Mutation: R15A | Summary: The R15A mutation inhibits nuclear entry of PTEN, indicating a change in its molecular function related to localization. Evidence Type: Functional | Mutation: E18A | Summary: The E18A mutation inhibits nuclear accumulation of PTEN, suggesting an alteration in its molecular function. Evidence Type: Functional | Mutation: D24A | Summary: The D24A mutation inhibits nuclear entry of PTEN, indicating a change in its molecular function. Evidence Type: Functional | Mutation: Y16A | Summary: The Y16A mutation inhibits nuclear entry of PTEN, suggesting an alteration in its molecular function. Evidence Type: Functional | Mutation: Y27A | Summary: The Y27A mutation inhibits nuclear entry of PTEN, indicating a change in its molecular function. Evidence Type: Functional | Mutation: I28A | Summary: The I28A mutation inhibits nuclear entry of PTEN, suggesting an alteration in its molecular function. Evidence Type: Functional | Mutation: N31A | Summary: The N31A mutation inhibits nuclear entry of PTEN, indicating a change in its molecular function. Evidence Type: Functional | Mutation: I32A | Summary: The I32A mutation inhibits nuclear entry of PTEN, suggesting an alteration in its molecular function. Evidence Type: Functional | Mutation: I33A | Summary: The I33A mutation inhibits nuclear entry of PTEN, indicating a change in its molecular function. Evidence Type: Functional | Mutation: P30A | Summary: The P30A mutation inhibits nuclear entry of PTEN, suggesting an alteration in its molecular function. Evidence Type: Functional | Mutation: N12A | Summary: The N12A mutation inhibits nuclear accumulation of PTEN, indicating a change in its molecular function. Evidence Type: Functional | Mutation: M35A | Summary: The M35A mutation inhibits nuclear accumulation of PTEN, suggesting an alteration in its molecular function.

Gene→Variant (gene-first): 5728:A39V 5728:Ala residues were mutated to Val 71:D19A 5728:D24A 5728:E18A 5728:F21A 5728:G20A 5728:I28A 5728:I32A 5728:I33A 5728:K13A 5728:L42A 5728:M35A 5728:N12A 5728:N31A 5728:P30A 100329167:R14A 5728:R15A 5728:Y16A 5728:Y27A

Genes: 5728 71 100329167

Variants: A39V Ala residues were mutated to Val D19A D24A E18A F21A G20A I28A I32A I33A K13A L42A M35A N12A N31A P30A R14A R15A Y16A Y27A

[Paragraph-level] PMCID: PMC4398541 Section: RESULTS PassageIndex: 5

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: K13E | Summary: The K13E mutation totally abrogated PTEN activity in a yeast model, indicating a significant alteration in molecular function. Evidence Type: Functional | Mutation: R15I | Summary: The R15I mutation totally abrogated PTEN activity in a yeast model, indicating a significant alteration in molecular function. Evidence Type: Functional | Mutation: R15S | Summary: The R15S mutation totally abrogated PTEN activity in a yeast model, indicating a significant alteration in molecular function. Evidence Type: Functional | Mutation: D24Y | Summary: The D24Y mutation totally abrogated PTEN activity in a yeast model, indicating a significant alteration in molecular function. Evidence Type: Functional | Mutation: I33S | Summary: The I33S mutation totally abrogated PTEN activity in a yeast model, indicating a significant alteration in molecular function. Evidence Type: Functional | Mutation: A34D | Summary: The A34D mutation totally abrogated PTEN activity in a yeast model, indicating a significant alteration in molecular function. Evidence Type: Functional | Mutation: M35R | Summary: The M35R mutation totally abrogated PTEN activity in a yeast model, indicating a significant alteration in molecular function. Evidence Type: Functional | Mutation: G36R | Summary: The G36R mutation totally abrogated PTEN activity in a yeast model, indicating a significant alteration in molecular function. Evidence Type: Functional | Mutation: L42P | Summary: The L42P mutation totally abrogated PTEN activity in a yeast model, indicating a significant alteration in molecular function. Evidence Type: Functional | Mutation: S10N | Summary: The S10N mutation partially reduced PTEN activity in a yeast model, indicating a moderate alteration in molecular function. Evidence Type: Functional | Mutation: Y16C | Summary: The Y16C mutation partially reduced PTEN activity in a yeast model, indicating a moderate alteration in molecular function. Evidence Type: Functional | Mutation: L23F | Summary: The L23F mutation partially reduced PTEN activity in a yeast model, indicating a moderate alteration in molecular function. Evidence Type: Functional | Mutation: A34V | Summary: The A34V mutation partially reduced PTEN activity in a yeast model, indicating a moderate alteration in molecular function.

Gene→Variant (gene-first): 5728:A34D 5728:A34V 5728:D24Y 5728:G36R 5728:I33S 5728:K13E 5728:L23F 5728:L42P 5728:M35R 5728:R15I 5728:R15S 5728:S10N 5728:Y16C

Genes: 5728

Variants: A34D A34V D24Y G36R I33S K13E L23F L42P M35R R15I R15S S10N Y16C

[Paragraph-level] PMCID: PMC4398541 Section: RESULTS PassageIndex: 4

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: L23F | Summary: The L23F mutation showed increased nuclear localization of PTEN, indicating an alteration in molecular function related to subcellular localization. Evidence Type: Functional | Mutation: M35R | Summary: The M35R mutation demonstrated increased nuclear localization of PTEN, suggesting a change in its molecular function. Evidence Type: Functional | Mutation: G36R | Summary: The G36R mutation resulted in increased nuclear localization of PTEN, reflecting an alteration in its molecular function. Evidence Type: Functional | Mutation: K13E | Summary: The K13E mutation fully abrogated the nuclear accumulation of PTEN 1-375, indicating a significant change in its molecular function. Evidence Type: Functional | Mutation: A34D | Summary: The A34D mutation fully abrogated the nuclear accumulation of PTEN 1-375, suggesting an alteration in its molecular function. Evidence Type: Functional | Mutation: L42P | Summary: The L42P mutation fully abrogated the nuclear accumulation of PTEN 1-375, indicating a change in its molecular function. Evidence Type: Functional | Mutation: R15I | Summary: The R15I mutation caused a partial inhibition of nuclear accumulation of PTEN, reflecting an alteration in its molecular function. Evidence Type: Functional | Mutation: R15S | Summary: The R15S mutation resulted in a partial inhibition of nuclear accumulation of PTEN, indicating a change in its molecular function. Evidence Type: Functional | Mutation: D24Y | Summary: The D24Y mutation caused a partial inhibition of nuclear accumulation of PTEN, suggesting an alteration in its molecular function. Evidence Type: Functional | Mutation: I33S | Summary: The I33S mutation resulted in a partial inhibition of nuclear accumulation of PTEN, indicating a change in its molecular function. Evidence Type: Functional | Mutation: S10N | Summary: The S10N mutation did not significantly alter the nuclear/cytoplasmic distribution of PTEN, suggesting no functional change. Evidence Type: Functional | Mutation: Y16C | Summary: The Y16C mutation did not significantly alter the nuclear/cytoplasmic distribution of PTEN, indicating no functional change. Evidence Type: Functional | Mutation: A34V | Summary: The A34V mutation did not significantly alter the nuclear/cytoplasmic distribution of PTEN, suggesting no functional change.

Gene→Variant (gene-first): 5728:A34D 5728:A34V 5728:D24Y 5728:G36R 5728:I33S 5728:K13E 5728:L23F 5728:L42P 5728:M35R 5728:R15I 5728:R15S 5728:S10N 5728:Y16C

Genes: 5728

Variants: A34D A34V D24Y G36R I33S K13E L23F L42P M35R R15I R15S S10N Y16C

[Paragraph-level] PMCID: PMC2736831 Section: ABSTRACT PassageIndex: 8

Evidence Type(s): Predictive, Diagnostic

Summary: Evidence Type: Predictive | Mutation: V600E | Summary: The BRAF V600E mutation may correlate with response to anti-EGFR monoclonal antibodies, suggesting its role in optimizing patient selection for therapy. Evidence Type: Diagnostic | Mutation: V600E | Summary: The assessment of the BRAF V600E mutation can aid in defining and classifying patients for treatment, indicating its diagnostic utility in patient selection.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paragraph-level] PMCID: PMC2736831 Section: ABSTRACT PassageIndex: 4

Evidence Type(s): Predictive

Summary: Evidence Type: Predictive | Mutation: V600E | Summary: The BRAF V600E mutation is associated with predicting resistance to cetuximab plus irinotecan therapy in a specific patient cohort.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paragraph-level] PMCID: PMC2736831 Section: ABSTRACT PassageIndex: 2

Evidence Type(s): Predictive

Summary: Evidence Type: Predictive | Mutation: V600E | Summary: The BRAF V600E mutation has been associated with resistance to anti-EGFR monoclonal antibodies in metastatic colorectal cancer, indicating its predictive value regarding therapy response. Evidence Type: Predictive | Mutation: KRAS codons 12 and 13 | Summary: KRAS codons 12 and 13 mutations predict resistance to anti-EGFR monoclonal antibodies in metastatic colorectal cancer, highlighting their predictive role in treatment response.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paragraph-level] PMCID: PMC2570525 Section: RESULTS PassageIndex: 6

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: AKT1 E17K | Summary: The expression of AKT1 E17K protein in NIH 3T3 cells increased AKT phosphorylation, indicating that this variant alters molecular function. Evidence Type: Functional | Mutation: AKT3 E17K | Summary: The expression of AKT3 E17K in A375 cells also increased AKT phosphorylation compared to wild-type AKT3, demonstrating a change in molecular function due to this variant.

Gene→Variant (gene-first): 207:AKT1 E17K 207:E17K

Genes: 207

Variants: AKT1 E17K E17K

[Paragraph-level] PMCID: PMC2570525 Section: RESULTS PassageIndex: 5

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: E17K | Summary: The E17K mutation is associated with the activation of AKT3, indicating that it alters molecular or biochemical function. Evidence Type: Oncogenic | Mutation: E17K | Summary: The E17K mutation contributes to tumor development or progression through the activation of AKT3.

Gene→Variant (gene-first): 207:E17K

Genes: 207

Variants: E17K

[Paragraph-level] PMCID: PMC2570525 Section: RESULTS PassageIndex: 4

Evidence Type(s): None

Summary: Not enough information in this passage.

Gene→Variant (gene-first): 207:AKT1 E17K 207:E17K

Genes: 207

Variants: AKT1 E17K E17K

[Paragraph-level] PMCID: PMC2570525 Section: RESULTS PassageIndex: 3

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: E17K (AKT1) | Summary: The AKT1 E17K mutation was identified in a lymph node metastasis, indicating its potential role in tumor development or progression. Evidence Type: Oncogenic | Mutation: E17K (AKT3) | Summary: The AKT3 E17K mutation was found in lymph node metastases, suggesting its contribution to tumor development or progression.

Gene→Variant (gene-first): 207:E17K

Genes: 207

Variants: E17K

[Paragraph-level] PMCID: PMC2570525 Section: RESULTS PassageIndex: 2

Evidence Type(s): Diagnostic

Summary: Evidence Type: Diagnostic | Mutation: AKT1 E17K | Summary: The AKT1 E17K mutation is mentioned in the context of detection in melanoma, suggesting its role in defining or classifying the disease.

Gene→Variant (gene-first): 207:AKT1 E17K 207:E17K

Genes: 207

Variants: AKT1 E17K E17K

[Paragraph-level] PMCID: PMC7211323 Section: RESULTS PassageIndex: 11

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: c.285delA | Summary: The mutation c.285delA results in no detectable protein band, indicating that it alters the molecular function of the ACVR2A gene product, likely leading to degradation through nonsense-mediated decay. Evidence Type: Functional | Mutation: 1310AA | Summary: The mutation 1310AA is associated with the production of truncated ACVR2A protein, suggesting that it alters the molecular function of the ACVR2A gene product.

Gene→Variant (gene-first): 92:1310AA 92:c.285delA

Genes: 92

Variants: 1310AA c.285delA

[Paragraph-level] PMCID: PMC7211323 Section: RESULTS PassageIndex: 9

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: 1310delA | Summary: The mutation 1310delA is identified as a hotspot mutation in the ACVR2A gene, contributing to tumor development in gastric cancer patients. Evidence Type: Oncogenic | Mutation: c.1309-1310delAA | Summary: The mutation c.1309-1310delAA is a hotspot mutation in the ACVR2A gene, associated with tumor progression in gastric cancer. Evidence Type: Oncogenic | Mutation: c.285delA | Summary: The mutation c.285delA is recognized as a hotspot mutation in the ACVR2A gene, playing a role in the development of gastric cancer. Evidence Type: Oncogenic | Mutation: p. D96Tfs54 | Summary: The mutation p. D96Tfs54 is a frameshift mutation in the ACVR2A gene, contributing to oncogenic processes in gastric cancer.

Gene→Variant (gene-first): 92:1310delA 92:c.1309-1310delAA 92:c.285delA 92:p. D96Tfs*54

Genes: 92

Variants: 1310delA c.1309-1310delAA c.285delA p. D96Tfs*54

[Paragraph-level] PMCID: PMC7211323 Section: RESULTS PassageIndex: 3

Evidence Type(s): Diagnostic

Summary: Evidence Type: Diagnostic | Mutation: 1309-1310delAA | Summary: The mutation 1309-1310delAA is associated with the MSI-H subtype of gastric cancers, indicating its role in classifying the disease. Evidence Type: Diagnostic | Mutation: c.1310delA | Summary: The mutation c.1310delA is linked to the MSI-H subtype of gastric cancers, supporting its use in disease classification. Evidence Type: Diagnostic | Mutation: c.285delA | Summary: The mutation c.285delA is associated with the MSI-H subtype of gastric cancers, indicating its relevance in disease classification.

Gene→Variant (gene-first): 92:1309-1310delAA 92:c.1310delA 92:c.285delA

Genes: 92

Variants: 1309-1310delAA c.1310delA c.285delA

[Paragraph-level] PMCID: PMC4654747 Section: RESULTS PassageIndex: 14

Evidence Type(s): Prognostic, Predictive, Oncogenic

Summary: Evidence Type: Prognostic | Mutation: K27M | Summary: The K27M mutation in histone H3.1 is associated with a better overall survival length compared to H3.3-K27M, indicating its prognostic significance in disease outcome. Evidence Type: Predictive | Mutation: K27M | Summary: Patients with the H3.1-K27M mutation show a better clinical response to radiotherapy, suggesting that this mutation may predict treatment response. Evidence Type: Oncogenic | Mutation: K27M | Summary: The K27M mutation in histone H3 is implicated in tumor development and progression, contributing to the oncogenic characteristics of the tumors.

Gene→Variant (gene-first): 3021:K27M

Genes: 3021

Variants: K27M

[Paragraph-level] PMCID: PMC4654747 Section: RESULTS PassageIndex: 13

Evidence Type(s): Prognostic

Summary: Evidence Type: Prognostic | Mutation: K27M | Summary: The K27M mutation is associated with a less aggressive behavior in diffuse intrinsic pontine glioma (DIPG), indicating its correlation with disease outcome independent of therapy.

Gene→Variant (gene-first): 3021:K27M

Genes: 3021

Variants: K27M

[Paragraph-level] PMCID: PMC4654747 Section: RESULTS PassageIndex: 11

Evidence Type(s): Diagnostic, Prognostic, Functional

Summary: Evidence Type: Diagnostic | Mutation: K27M | Summary: The K27M mutation is associated with the proneural-glioblastoma multiforme subtype, indicating its role in classifying and defining this specific disease subtype. Evidence Type: Prognostic | Mutation: K27M | Summary: The presence of the K27M mutation correlates with disease outcome, as indicated by the clinico-radiological follow-up of DIPG patients showing a significant association with metastatic relapse. Evidence Type: Functional | Mutation: K27M | Summary: The K27M mutation is linked to alterations in molecular functions, specifically affecting adhesion properties and deregulating genes related to migration and invasion in tumors.

Gene→Variant (gene-first): 3021:K27M

Genes: 3021

Variants: K27M

[Paragraph-level] PMCID: PMC4654747 Section: RESULTS PassageIndex: 10

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: K27M | Summary: The K27M mutation is associated with driving distinct oncogenic programs, indicating its role in tumor development or progression.

Gene→Variant (gene-first): 3021:K27M

Genes: 3021

Variants: K27M

[Paragraph-level] PMCID: PMC4654747 Section: RESULTS PassageIndex: 9

Evidence Type(s): Oncogenic, Diagnostic

Summary: Evidence Type: Oncogenic | Mutation: K27M | Summary: The K27M mutation is associated with specific tumor subgroups (H3.1 and H3.3) and is implicated in tumor development, particularly in the context of DIPG and pHGG. Evidence Type: Diagnostic | Mutation: K27M | Summary: The K27M mutation is used to classify and define specific tumor subtypes, particularly in H3.1 and H3.3 tumors, indicating its role in disease classification.

Gene→Variant (gene-first): 3021:K27M

Genes: 3021

Variants: K27M

[Paragraph-level] PMCID: PMC4654747 Section: RESULTS PassageIndex: 5

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: H3.3-K27M | Summary: The H3.3-K27M mutation is associated with midline tumors, indicating its contribution to tumor development or progression. Evidence Type: Oncogenic | Mutation: H3-G34R/V | Summary: The H3-G34R/V mutations are restricted to cerebral hemispheres, suggesting their role in tumor development or progression. Evidence Type: Oncogenic | Mutation: H3.3-K27I | Summary: The H3.3-K27I mutation is found in pontine tumors, indicating its contribution to tumor development or progression.

Gene→Variant (gene-first): 3196:G34R/V 3021:K27I 3021:K27M

Genes: 3196 3021

Variants: G34R/V K27I K27M

[Paragraph-level] PMCID: PMC4654747 Section: RESULTS PassageIndex: 4

Evidence Type(s): Diagnostic, Oncogenic, Functional

Summary: Evidence Type: Diagnostic | Mutation: K27M | Summary: The H3-K27M mutation is used to classify and define a subtype of tumors, as it can be accurately detected by immunohistochemistry (IHC). Evidence Type: Oncogenic | Mutation: K27M | Summary: The H3-K27M mutation contributes to tumor development or progression, as indicated by its presence in tumor cells. Evidence Type: Functional | Mutation: K27I | Summary: The K27I mutation results in a loss of H3K27me3 immunoexpression, indicating an alteration in molecular function. Evidence Type: Functional | Mutation: 83A>T | Summary: The nucleotide change 83A>T is part of the K27I mutation and contributes to the alteration in molecular function. Evidence Type: Functional | Mutation: 84G>T | Summary: The nucleotide change 84G>T is part of the K27I mutation and contributes to the alteration in molecular function.

Gene→Variant (gene-first): 7157:83A>T 4613:84G>T 3021:K27I 3021:K27M 126961:lysine-to-isoleucine

Genes: 7157 4613 3021 126961

Variants: 83A>T 84G>T K27I K27M lysine-to-isoleucine

[Paragraph-level] PMCID: PMC4654747 Section: RESULTS PassageIndex: 3

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: K27M | Summary: The H3-K27M mutation is associated with tumor development in DIPG, as indicated by its detection in biopsy samples and correlation with histological features. Evidence Type: Functional | Mutation: K27M | Summary: The K27M mutation alters the trimethylation status of histone H3, impacting molecular function related to gene regulation in tumor cells.

Gene→Variant (gene-first): 3021:K27M 3021:lysine 27

Genes: 3021

Variants: K27M lysine 27

[Paragraph-level] PMCID: PMC4654747 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Oncogenic, Prognostic

Summary: Evidence Type: Oncogenic | Mutation: K27M | Summary: The K27M mutation in H3.3 (H3F3A) contributes to tumor development and progression in diffuse intrinsic pontine glioma (DIPG), driving distinct oncogenic programs. Evidence Type: Oncogenic | Mutation: K27I | Summary: The K27I mutation in H3F3A is associated with tumor development in DIPG, contributing to the loss of trimethylation and driving oncogenic behavior. Evidence Type: Prognostic | Mutation: K27M | Summary: Patients with tumors harboring the K27M mutation in H3.3 exhibited significantly earlier relapse and more metastatic recurrences, indicating a poor prognosis.

Gene→Variant (gene-first): 3021:K27I 3021:K27M 126961:lysine-to-isoleucine

Genes: 3021 126961

Variants: K27I K27M lysine-to-isoleucine

[Paragraph-level] PMCID: PMC6549573 Section: RESULTS PassageIndex: 12

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: G12D | Summary: The KRAS G12D mutation is identified as contributing to tumor development or progression, particularly in the context of patients with KRAS G12D-mutant disease.

Gene→Variant (gene-first): 3845:G12D

Genes: 3845

Variants: G12D

[Paragraph-level] PMCID: PMC6549573 Section: RESULTS PassageIndex: 11

Evidence Type(s): Prognostic, Oncogenic

Summary: Evidence Type: Prognostic | Mutation: G12D | Summary: The KRAS G12D mutation is associated with prolonged survival in models with p53 deficiency, indicating a correlation with disease outcome independent of therapy. Evidence Type: Oncogenic | Mutation: G12D | Summary: The KRAS G12D mutation contributes to tumor development or progression, as evidenced by its presence in tumor models.

Gene→Variant (gene-first): 3845:G12D

Genes: 3845

Variants: G12D

[Paragraph-level] PMCID: PMC6549573 Section: RESULTS PassageIndex: 8

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: G12D | Summary: The KRAS G12D mutation was associated with a lack of response to bortezomib in the majority of patients, indicating its potential predictive value regarding therapy response. Evidence Type: Oncogenic | Mutation: G12D | Summary: The KRAS G12D mutation is implicated in the development and progression of lung adenocarcinoma, supporting its classification as an oncogenic variant.

Gene→Variant (gene-first): 3845:G12D

Genes: 3845

Variants: G12D

[Paragraph-level] PMCID: PMC6549573 Section: RESULTS PassageIndex: 4

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: G12D | Summary: The KRAS G12D mutation is associated with response evaluation to bortezomib therapy in lung cancer patients, indicating its potential predictive value for treatment response. Evidence Type: Oncogenic | Mutation: G12D | Summary: The KRAS G12D mutation is implicated in the development of lung cancers, supporting its classification as an oncogenic variant.

Gene→Variant (gene-first): 3845:G12D

Genes: 3845

Variants: G12D

[Paragraph-level] PMCID: PMC6549573 Section: RESULTS PassageIndex: 3

Evidence Type(s): Oncogenic, Predictive

Summary: Evidence Type: Oncogenic | Mutation: G12D | Summary: The KRAS G12D mutation is associated with lung adenocarcinoma and contributes to tumor development in patients with stage IV disease. Evidence Type: Predictive | Mutation: G12D | Summary: The presence of the KRAS G12D mutation in patients with lung cancer may correlate with response to treatment with bortezomib, indicating its predictive value for therapy outcomes.

Gene→Variant (gene-first): 3845:G12D

Genes: 3845

Variants: G12D

[Paragraph-level] PMCID: PMC4320693 Section: RESULTS PassageIndex: 4

Evidence Type(s): Diagnostic

Summary: Evidence Type: Diagnostic | Mutation: p.His1047Arg | Summary: The mutation p.His1047Arg is associated with phenotypes such as FAO, Hemihyperplasia- Multiple Lipomatosis (HHML), or macrodactyly, indicating its role in defining or classifying these conditions. Evidence Type: Diagnostic | Mutation: p.His1047Leu | Summary: The mutation p.His1047Leu is linked to phenotypes consistent with FAO, Hemihyperplasia- Multiple Lipomatosis (HHML), or macrodactyly, suggesting its use in disease classification. Evidence Type: Diagnostic | Mutation: p.Glu542Lys | Summary: The mutation p.Glu542Lys is found in patients with phenotypes consistent with CLOVES syndrome, indicating its role in defining or classifying this condition. Evidence Type: Diagnostic | Mutation: p.Glu545Lys | Summary: The mutation p.Glu545Lys is associated with the CLOVES syndrome phenotype, supporting its use in disease classification. Evidence Type: Diagnostic | Mutation: p.Cys420Arg | Summary: The mutation p.Cys420Arg is identified in patients with CLOVES syndrome, indicating its relevance in defining or classifying this condition.

Gene→Variant (gene-first): 5290:p.Cys420Arg 5290:p.Glu542Lys 5290:p.Glu545Lys 5290:p.His1047Arg 5290:p.His1047Leu

Genes: 5290

Variants: p.Cys420Arg p.Glu542Lys p.Glu545Lys p.His1047Arg p.His1047Leu

[Paragraph-level] PMCID: PMC4320693 Section: RESULTS PassageIndex: 3

Evidence Type(s): Diagnostic

Summary: Evidence Type: Diagnostic | Mutation: p.His1047Arg | Summary: The p.His1047Arg (H1047R) mutation is associated with a significant proportion of patients, indicating its potential role in defining or classifying a disease or subtype. Evidence Type: Diagnostic | Mutation: p.His1047Leu | Summary: The p.His1047Leu (H1047L) mutation is present in a notable percentage of patients, suggesting its relevance in the diagnosis or classification of a disease or subtype. Evidence Type: Diagnostic | Mutation: p.Glu545Lys | Summary: The p.Glu545Lys (E545K) mutation is found in a smaller subset of patients, which may indicate its role in defining or classifying a disease or subtype. Evidence Type: Diagnostic | Mutation: p.Glu542Lys | Summary: The p.Glu542Lys (E542K) mutation occurs in a minority of patients, suggesting its potential use in the diagnosis or classification of a disease or subtype. Evidence Type: Diagnostic | Mutation: p.Cys420Arg | Summary: The p.Cys420Arg (C420R) mutation, although less common, may still play a role in defining or classifying a disease or subtype based on its occurrence in patients.

Gene→Variant (gene-first): 5290:C420R 5290:E542K 5290:E545K 5290:H1047L 5290:H1047R 5290:p.Cys420Arg 5290:p.Glu542Lys 5290:p.Glu545Lys 5290:p.His1047Arg 5290:p.His1047Leu

Genes: 5290

Variants: C420R E542K E545K H1047L H1047R p.Cys420Arg p.Glu542Lys p.Glu545Lys p.His1047Arg p.His1047Leu

[Paragraph-level] PMCID: PMC6173734 Section: RESULTS PassageIndex: 2

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: c.422G>A; p.Cys141Tyr | Summary: The TP53 missense variant c.422G>A (p.Cys141Tyr) is described as pathogenic and contributes to tumor development or progression, indicating its oncogenic potential.

Gene→Variant (gene-first): 7157:c.422G>A 7157:p.Cys141Tyr

Genes: 7157

Variants: c.422G>A p.Cys141Tyr

[Paragraph-level] PMCID: PMC7182441 Section: RESULTS PassageIndex: 5

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: S6 | Summary: The passage discusses the effects of alpha-MT on the phosphorylation status of S6 kinase in LS174T cells, indicating that the variant S6 is involved in the molecular function related to mTOR signaling and autophagy in response to amino acid starvation.

Gene→Variant (gene-first): 6198:S6

Genes: 6198

Variants: S6

[Paragraph-level] PMCID: PMC8453302 Section: ABSTRACT PassageIndex: 2

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: G292R | Summary: The G292R mutation in HER2 is associated with a positive response to pyrotinib in a metastatic cervical adenocarcinoma patient, indicating its predictive value for treatment efficacy. Evidence Type: Oncogenic | Mutation: G292R | Summary: The G292R mutation in HER2 is implicated in tumor development or progression in cervical cancer, supporting its classification as an oncogenic variant.

Gene→Variant (gene-first): 2064:G292R

Genes: 2064

Variants: G292R

[Paragraph-level] PMCID: PMC7064492 Section: RESULTS PassageIndex: 2

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: p.K57N | Summary: The MAP2K1 (p.K57N) mutation was found in the tissue adjacent to the cartilage in patients with auricular AVM, indicating its potential role in tumor development or progression. Evidence Type: Functional | Mutation: p.K57N | Summary: The presence of the MAP2K1 (p.K57N) mutation suggests alterations in molecular or biochemical function, as indicated by its enrichment in endothelial cells compared to non-endothelial cells.

Gene→Variant (gene-first): 5604:p.K57N

Genes: 5604

Variants: p.K57N

[Paragraph-level] PMCID: PMC4748120 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Oncogenic, Functional, Diagnostic

Summary: Evidence Type: Oncogenic | Mutation: A66dup | Summary: The A66dup mutation in K-Ras is associated with tumor development and progression, as it transforms the growth of primary myeloid progenitors and Ba/F3 cells, indicating its oncogenic potential. Evidence Type: Functional | Mutation: A66dup | Summary: The A66dup mutation alters the molecular function of K-Ras by reducing intrinsic GTP hydrolysis rates and impairing PI3 kinase binding, demonstrating its impact on biochemical activity. Evidence Type: Diagnostic | Mutation: A66dup | Summary: The presence of the A66dup mutation in K-Ras has diagnostic implications, as it is associated with an atypical myeloproliferative neoplasm in the patient described.

Gene→Variant (gene-first): 5295:A66dup

Genes: 5295

Variants: A66dup

[Paragraph-level] PMCID: PMC4899144 Section: RESULTS PassageIndex: 23

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: Y641F | Summary: The Ezh2Y641F mutation alters the molecular function of the enzyme, leading to a global redistribution of H3K27me3 marks across the genome in melanoma cell lines. Evidence Type: Oncogenic | Mutation: Y641F | Summary: The Ezh2Y641F mutation contributes to tumor development by affecting the epigenetic landscape, as indicated by changes in H3K27me3 distribution in melanoma cell lines.

Gene→Variant (gene-first): 2146:Y641F

Genes: 2146

Variants: Y641F

[Paragraph-level] PMCID: PMC4899144 Section: RESULTS PassageIndex: 22

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: Y641F | Summary: The Ezh2Y641F mutation alters the H3K27me3 signal around the transcription start site and gene body, indicating a change in molecular function related to gene expression regulation. Evidence Type: Oncogenic | Mutation: Y641F | Summary: The Ezh2Y641F mutation is associated with changes in gene expression in B-cells and melanoma cell lines, suggesting its role in tumor development or progression.

Gene→Variant (gene-first): 2146:Y641F

Genes: 2146

Variants: Y641F

[Paragraph-level] PMCID: PMC4899144 Section: RESULTS PassageIndex: 21

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: Y641F | Summary: The Ezh2Y641F mutation alters the distribution of H3K27me3 at promoter regions and affects gene expression, indicating a change in molecular function related to transcription regulation. Evidence Type: Oncogenic | Mutation: Y641F | Summary: The Ezh2Y641F mutation contributes to tumor development by affecting the expression of genes regulated by PRC2, suggesting its role in cancer progression.

Gene→Variant (gene-first): 2146:Y641F

Genes: 2146

Variants: Y641F

[Paragraph-level] PMCID: PMC4899144 Section: RESULTS PassageIndex: 15

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: Y641F | Summary: The Ezh2Y641F mutation alters the expression of numerous transcripts in both B-cells and melanoma cells, indicating a change in molecular function associated with this variant. Evidence Type: Oncogenic | Mutation: Y641F | Summary: The Ezh2Y641F mutation is implicated in tumor development as it is expressed in melanoma cell lines derived from tumors, suggesting a role in cancer progression.

Gene→Variant (gene-first): 2146:Y641F

Genes: 2146

Variants: Y641F

[Paragraph-level] PMCID: PMC4899144 Section: RESULTS PassageIndex: 13

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: Y641F | Summary: The Y641F mutation in EZH2 is associated with response to the EZH2 inhibitor JQEZ5, indicating its predictive value for treatment efficacy in B-cell lymphoma and melanoma models. Evidence Type: Oncogenic | Mutation: Y641F | Summary: The Y641F mutation in EZH2 contributes to tumor development in B-cell lymphoma, as evidenced by its presence in autochthonous tumor models.

Gene→Variant (gene-first): 2146:Y641F

Genes: 2146

Variants: Y641F

[Paragraph-level] PMCID: PMC4899144 Section: RESULTS PassageIndex: 12

Evidence Type(s): Predictive, Oncogenic, Functional

Summary: Evidence Type: Predictive | Mutation: Y641F | Summary: The Y641F mutation in Ezh2 is associated with increased sensitivity to the EZH2 inhibitor JQEZ5, indicating a correlation with treatment response. Evidence Type: Oncogenic | Mutation: Y641F | Summary: The Y641F mutation in Ezh2 is implicated in tumor initiation and maintenance, contributing to tumor development in melanoma. Evidence Type: Functional | Mutation: Y641F | Summary: The Y641F mutation alters the enzymatic activity of Ezh2, as evidenced by the differential response to EZH2 inhibitors in cell lines. Evidence Type: Predictive | Mutation: Y646F | Summary: The Y646F mutation exhibits in vitro activity against the JQEZ5 inhibitor, suggesting a correlation with treatment response. Evidence Type: Oncogenic | Mutation: Y646F | Summary: The Y646F mutation in Ezh2 is involved in tumor development and progression in melanoma. Evidence Type: Functional | Mutation: Y646F | Summary: The Y646F mutation affects the molecular function of Ezh2, as indicated by its response to pharmacological inhibitors.

Gene→Variant (gene-first): 2146:Y641F 2146:Y646F

Genes: 2146

Variants: Y641F Y646F

[Paragraph-level] PMCID: PMC4899144 Section: RESULTS PassageIndex: 10

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: B-RAFV600E | Summary: The B-RAFV600E mutation is implicated in oncogene-induced senescence and contributes to tumor development as indicated by its role in the experimental setup involving primary human melanocytes. Evidence Type: Oncogenic | Mutation: Y641F | Summary: The Y641F mutation in EZH2 is suggested to have oncogenic effects, as the experiments indicate that RAS-PI3K activation can attenuate its oncogenic effects in the context of melanoma formation.

Gene→Variant (gene-first): 673:B-RAFV600E 2146:Y641F

Genes: 673 2146

Variants: B-RAFV600E Y641F

[Paragraph-level] PMCID: PMC4899144 Section: RESULTS PassageIndex: 9

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: B-RafV600E | Summary: B-RafV600E is implicated in promoting melanoma through RAF/MEK/ERK activation, indicating its role in tumor development. Evidence Type: Oncogenic | Mutation: Ezh2Y641F | Summary: Ezh2Y641F is suggested to have oncogenic effects in melanoma formation, although its impact is rendered irrelevant in the presence of mutant RAS signaling.

Gene→Variant (gene-first): 673:B-RafV600E 2146:Y641F

Genes: 673 2146

Variants: B-RafV600E Y641F

[Paragraph-level] PMCID: PMC4899144 Section: RESULTS PassageIndex: 8

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: B-RAFV600E | Summary: The B-RAFV600E mutation is implicated in the majority of human melanomas and contributes to tumor development and progression. Evidence Type: Oncogenic | Mutation: Ezh2Y641F | Summary: The Ezh2Y641F mutation cooperates with the B-RAFV600E mutation to accelerate tumorigenesis in melanoma, indicating its role in cancer development. Evidence Type: Oncogenic | Mutation: B-RafV600E | Summary: The B-RafV600E mutation is associated with melanoma formation and progression, demonstrating its oncogenic potential.

Gene→Variant (gene-first): 673:B-RAFV600E 673:B-RafV600E 2146:Y641F

Genes: 673 2146

Variants: B-RAFV600E B-RafV600E Y641F

[Paragraph-level] PMCID: PMC4899144 Section: RESULTS PassageIndex: 6

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: Y641F | Summary: The Y641F mutation in EZH2 exhibits altered methylase activity, demonstrating a change in molecular function compared to wild-type EZH2. Evidence Type: Oncogenic | Mutation: Y641F | Summary: The presence of the Y641F mutation contributes to tumorigenesis, as evidenced by the development of splenomegaly and lymphadenopathy in mice harboring this mutation. Evidence Type: Functional | Mutation: Y646 | Summary: The passage suggests that mutations at position Y646 may also affect molecular function, although specific details are not provided.

Gene→Variant (gene-first): 2146:Y641F 2146:Y646 2146:tyrosine to phenylalanine

Genes: 2146

Variants: Y641F Y646 tyrosine to phenylalanine

[Paragraph-level] PMCID: PMC4899144 Section: RESULTS PassageIndex: 5

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: Y641F | Summary: The Ezh2Y641F mutation contributes to tumor development and progression in B-cell lymphomas, as indicated by its role in accelerating lymphoma formation when combined with other genetic alterations. Evidence Type: Functional | Mutation: Y641F | Summary: The Ezh2Y641F variant alters molecular function by affecting the global levels of H3K27me3, which is associated with apoptotic resistance and B-cell transformation.

Gene→Variant (gene-first): 2146:Y641F

Genes: 2146

Variants: Y641F

[Paragraph-level] PMCID: PMC4899144 Section: RESULTS PassageIndex: 4

Evidence Type(s): Oncogenic, Prognostic

Summary: Evidence Type: Oncogenic | Mutation: Y641F | Summary: The Ezh2Y641F mutation contributes to tumor development, as it induces highly penetrant B-cell lymphoma in mice, demonstrating its role in malignancy. Evidence Type: Prognostic | Mutation: Y641F | Summary: The presence of the Ezh2Y641F mutation correlates with a median survival of one year in tumor-bearing mice, indicating its association with disease outcome.

Gene→Variant (gene-first): 2146:Y641F

Genes: 2146

Variants: Y641F

[Paragraph-level] PMCID: PMC4899144 Section: RESULTS PassageIndex: 3

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: Y641F | Summary: The Y641F mutation alters molecular function, as it is associated with a gain-of-function effect, leading to increased H3K27me3 levels in B-cells. Evidence Type: Oncogenic | Mutation: Y641F | Summary: The Y641F mutation is equivalent to a common EZH2 missense mutation found in human cancers, indicating its contribution to tumor development. Evidence Type: Functional | Mutation: Y646F | Summary: The Y646F mutation is described as equivalent to the Y641F mutation, suggesting it also alters molecular function, although specific functional data for Y646F is not detailed in the passage. Evidence Type: Oncogenic | Mutation: Y646F | Summary: The Y646F mutation is noted as one of the most common EZH2 missense mutations in human cancers, indicating its role in tumor development.

Gene→Variant (gene-first): 2146:Y641F 2146:Y646F

Genes: 2146

Variants: Y641F Y646F

[Paragraph-level] PMCID: PMC7074098 Section: RESULTS PassageIndex: 9

Evidence Type(s): Prognostic

Summary: Evidence Type: Prognostic | Mutation: I643T | Summary: The I643T mutation is part of a group of BAP1 mutations that were not associated with overall survival in cutaneous melanoma (CM), indicating it does not correlate with disease outcome. Evidence Type: Prognostic | Mutation: E30K | Summary: The E30K mutation is included in the BAP1 mutations that were not associated with overall survival in CM, suggesting it does not correlate with disease outcome. Evidence Type: Prognostic | Mutation: P629S | Summary: The P629S mutation is among the BAP1 mutations that were not associated with overall survival in CM, indicating it does not correlate with disease outcome. Evidence Type: Prognostic | Mutation: R417M | Summary: The R417M mutation is part of the BAP1 mutations that were not associated with overall survival in CM, suggesting it does not correlate with disease outcome. Evidence Type: Prognostic | Mutation: S143N | Summary: The S143N mutation is included in the BAP1 mutations that were not associated with overall survival in CM, indicating it does not correlate with disease outcome. Evidence Type: Prognostic | Mutation: L416F | Summary: The L416F mutation is part of the BAP1 mutations that were not associated with overall survival in CM, suggesting it does not correlate with disease outcome. Evidence Type: Prognostic | Mutation: R59W | Summary: The R59W mutation is included in the BAP1 mutations that were not associated with overall survival in CM, indicating it does not correlate with disease outcome.

Gene→Variant (gene-first): 8314:E30K 8314:I643T 8314:L416F 8314:P629S 8314:R417M 8314:R59W 6490:S143N

Genes: 8314 6490

Variants: E30K I643T L416F P629S R417M R59W S143N

[Paragraph-level] PMCID: PMC8033310 Section: RESULTS PassageIndex: 11

Evidence Type(s): Diagnostic

Summary: Evidence Type: Diagnostic | Mutation: E545K | Summary: The E545K mutation is associated with the diagnosis of invasive cancer in patients with PIK3CA mutations, as indicated by its presence in the cohort studied. Evidence Type: Diagnostic | Mutation: H1047R | Summary: The H1047R mutation is also linked to the diagnosis of invasive cancer in patients with PIK3CA mutations, as observed in the cohort analyzed.

Gene→Variant (gene-first): 5290:E545K 5290:H1047R

Genes: 5290

Variants: E545K H1047R

[Paragraph-level] PMCID: PMC8033310 Section: RESULTS PassageIndex: 6

Evidence Type(s): Predictive, Oncogenic, Functional

Summary: Evidence Type: Predictive | Mutation: E545K | Summary: The PIK3CA E545K mutation is associated with induced resistance to chemotherapy in TNBC cells, suggesting a correlation with treatment response. Evidence Type: Oncogenic | Mutation: E545K | Summary: The PIK3CA E545K mutation contributes to tumor development and progression, as indicated by the increased tumor volume in experimental models. Evidence Type: Functional | Mutation: E545K | Summary: The PIK3CA E545K mutation alters molecular function by downregulating Caspase 3 and upregulating Xiap in tumor tissues, affecting apoptosis.

Gene→Variant (gene-first): 5290:E545K

Genes: 5290

Variants: E545K

[Paragraph-level] PMCID: PMC8033310 Section: RESULTS PassageIndex: 5

Evidence Type(s): Oncogenic, Predictive

Summary: Evidence Type: Oncogenic | Mutation: E545K | Summary: The PIK3CA E545K mutation is associated with promoting growth and inhibiting apoptosis in TNBC cell lines, indicating its role in tumor development and progression. Evidence Type: Predictive | Mutation: E545K | Summary: The presence of the PIK3CA E545K mutation correlates with decreased sensitivity to chemotherapy, suggesting it may influence treatment response in TNBC patients.

Gene→Variant (gene-first): 5290:E545K

Genes: 5290

Variants: E545K

[Paragraph-level] PMCID: PMC8033310 Section: RESULTS PassageIndex: 3

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: E545K | Summary: The PIK3CAE545K mutation was shown to alter cell viability and apoptosis in TNBC cell lines, indicating a change in molecular function related to cell proliferation and survival. Evidence Type: Oncogenic | Mutation: E545K | Summary: The PIK3CAE545K mutation contributes to tumor development by enhancing the aggressiveness and migratory phenotype of TNBC cells.

Gene→Variant (gene-first): 5290:E545K

Genes: 5290

Variants: E545K

[Paragraph-level] PMCID: PMC11272140 Section: RESULTS PassageIndex: 10

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: G2032R | Summary: The G2032R mutation is identified as a ROS1 resistance mutation in crizotinib-pretreated patients, indicating its role in tumor progression and resistance to therapy. Evidence Type: Oncogenic | Mutation: L2026M | Summary: The L2026M mutation is also noted as a ROS1 resistance mutation in crizotinib-pretreated patients, contributing to tumor development and resistance. Evidence Type: Oncogenic | Mutation: S1986F | Summary: The S1986F mutation is classified as a ROS1 resistance mutation in crizotinib-pretreated patients, suggesting its involvement in tumor progression and resistance mechanisms. Evidence Type: Oncogenic | Mutation: G2101A | Summary: The G2101A mutation, detected in a patient with crizotinib resistance, is implicated in tumor development and progression as a ROS1 resistance mutation.

Gene→Variant (gene-first): 6098:G2032R 4914:G2101A 7294:L2026M 7294:S1986F

Genes: 6098 4914 7294

Variants: G2032R G2101A L2026M S1986F

[Paragraph-level] PMCID: PMC4868698 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Functional, Predictive, Oncogenic

Summary: Evidence Type: Functional | Mutation: S703I | Summary: The JAK1S703I mutation alters the molecular function by activating the JAK-STAT signaling pathway and driving cell proliferation in vitro. Evidence Type: Predictive | Mutation: S703I | Summary: The JAK1S703I mutation correlates with sensitivity to the JAK1/2 inhibitor ruxolitinib, indicating its potential as a predictive biomarker for therapy response in HCC. Evidence Type: Oncogenic | Mutation: S703I | Summary: The JAK1S703I mutation contributes to tumor development by activating the JAK-STAT signaling pathway, which is associated with cell proliferation in the absence of cytokine stimulation.

Gene→Variant (gene-first): 3716:S703I

Genes: 3716

Variants: S703I

[Paragraph-level] PMCID: PMC4239128 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: V600E | Summary: The BRAF V600E mutation is associated with the patient's response to dual therapy with dabrafenib and trametinib, indicating its predictive value for treatment efficacy. Evidence Type: Oncogenic | Mutation: V600E | Summary: The BRAF V600E mutation contributes to the development and progression of the poorly differentiated intrahepatic cholangiocarcinoma in this patient.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paragraph-level] PMCID: PMC3422615 Section: RESULTS PassageIndex: 12

Evidence Type(s): Prognostic, Oncogenic

Summary: Evidence Type: Prognostic | Mutation: K27M | Summary: The K27M-H3.3 mutation correlates with significantly worse overall survival in DIPG patients compared to wild-type tumors, indicating its role as a prognostic factor for disease outcome. Evidence Type: Oncogenic | Mutation: K27M | Summary: The K27M-H3.3 mutation contributes to tumor development or progression in DIPG, as evidenced by its association with poor survival outcomes in affected patients.

Gene→Variant (gene-first): 3021:K27M

Genes: 3021

Variants: K27M

[Paragraph-level] PMCID: PMC3422615 Section: RESULTS PassageIndex: 10

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: K27M | Summary: The K27M mutation is associated with significant focal copy number alterations and is implicated in tumor development, particularly in the context of H3.3 mutant groups.

Gene→Variant (gene-first): 3021:K27M

Genes: 3021

Variants: K27M

[Paragraph-level] PMCID: PMC3422615 Section: RESULTS PassageIndex: 9

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: K27M | Summary: The K27M-H3.3 mutation is associated with specific chromosomal alterations that contribute to tumor development in DIPG samples. Evidence Type: Functional | Mutation: K27M | Summary: The K27M mutation alters molecular characteristics in H3.3, impacting the biochemical function relevant to tumor biology.

Gene→Variant (gene-first): 3021:K27M

Genes: 3021

Variants: K27M

[Paragraph-level] PMCID: PMC3422615 Section: RESULTS PassageIndex: 7

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: K27M | Summary: The K27M mutation in H3.3 is associated with DIPG samples and contributes to tumor development or progression, as indicated by its presence in a significant number of cases.

Gene→Variant (gene-first): 3021:K27M

Genes: 3021

Variants: K27M

[Paragraph-level] PMCID: PMC3422615 Section: RESULTS PassageIndex: 5

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: G34V/R | Summary: The G34V/R mutation is associated with GBM samples that also carry ATRX and TP53 mutations, indicating its contribution to tumor development. Evidence Type: Oncogenic | Mutation: K27M | Summary: The K27M mutation is found in DIPG samples that also harbor ATRX mutations, suggesting its role in tumor progression.

Gene→Variant (gene-first): 3021:G34V/R 3021:K27M

Genes: 3021

Variants: G34V/R K27M

[Paragraph-level] PMCID: PMC3422615 Section: RESULTS PassageIndex: 3

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: K27M | Summary: The K27M mutation in Histone H3.3 is recurrently identified in DIPG samples, indicating its contribution to tumor development and progression.

Gene→Variant (gene-first): 3021:G34V/R 3021:K27M

Genes: 3021

Variants: G34V/R K27M

[Paragraph-level] PMCID: PMC10524391 Section: ABSTRACT PassageIndex: 6

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: C797S | Summary: The C797S mutation is associated with resistance to osimertinib, indicating its predictive value in therapy response. Evidence Type: Oncogenic | Mutation: C797S | Summary: The C797S mutation contributes to tumor progression in the context of EGFR-mutant lung cancers. Evidence Type: Oncogenic | Mutation: G12S | Summary: The G12S mutation is implicated in tumor development as part of off-target resistance mechanisms. Evidence Type: Oncogenic | Mutation: G810S | Summary: The G810S mutation is associated with tumor progression in RET fusion-positive lung cancers. Evidence Type: Oncogenic | Mutation: T790M | Summary: The T790M mutation is known to contribute to tumor development and resistance in EGFR-mutant lung cancers. Evidence Type: Oncogenic | Mutation: V600E | Summary: The V600E mutation is recognized for its role in tumor progression as part of off-target resistance mechanisms.

Gene→Variant (gene-first): 1956:C797S 3845:G12S 5979:G810S 1956:T790M 673:V600E

Genes: 1956 3845 5979 673

Variants: C797S G12S G810S T790M V600E

[Paragraph-level] PMCID: PMC10524391 Section: RESULTS PassageIndex: 26

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: C797S | Summary: The EGFR C797S mutation is associated with resistance mechanisms, indicating its potential role in treatment response. Evidence Type: Oncogenic | Mutation: V600E | Summary: The BRAF V600E mutation is implicated in tumor development and progression, contributing to oncogenic processes. Evidence Type: Oncogenic | Mutation: V804E | Summary: The RET V804E mutation is associated with tumor development, indicating its role as an oncogenic driver. Evidence Type: Oncogenic | Mutation: V804M | Summary: The RET V804M mutation is also linked to tumor development, supporting its classification as an oncogenic variant. Evidence Type: Oncogenic | Mutation: G12S | Summary: The KRAS G12S mutation is recognized for its contribution to tumor development, marking it as an oncogenic variant. Evidence Type: Oncogenic | Mutation: G810S | Summary: The RET G810S mutation is associated with tumor progression, reinforcing its role as an oncogenic driver.

Gene→Variant (gene-first): 1956:C797S 3845:G12S 5979:G810S 673:V600E 5979:V804E 5979:V804M

Genes: 1956 3845 5979 673

Variants: C797S G12S G810S V600E V804E V804M

[Paragraph-level] PMCID: PMC10524391 Section: RESULTS PassageIndex: 25

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: G12S | Summary: The KRAS G12S mutation is associated with tumor development or progression as it is mentioned in the context of off-target resistance involving receptor tyrosine kinase or MAPK pathway activation. Evidence Type: Oncogenic | Mutation: V600E | Summary: The BRAF V600E mutation is identified as a hotspot mutation contributing to tumor development or progression, as indicated by its presence in cases of off-target resistance.

Gene→Variant (gene-first): 3845:G12S 673:V600E

Genes: 3845 673

Variants: G12S V600E

[Paragraph-level] PMCID: PMC10524391 Section: RESULTS PassageIndex: 24

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: G810S | Summary: The acquired RET G810S mutation is noted in the context of tumor progression, suggesting its contribution to tumor development or progression.

Gene→Variant (gene-first): 5979:G810S

Genes: 5979

Variants: G810S

[Paragraph-level] PMCID: PMC10524391 Section: RESULTS PassageIndex: 23

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: C797S | Summary: The C797S mutation is associated with resistance to therapeutic EGFR engagement, indicating its role in treatment response. Evidence Type: Predictive | Mutation: T790M | Summary: The T790M mutation is implicated in resistance to therapeutic EGFR engagement, suggesting its relevance in treatment response. Evidence Type: Oncogenic | Mutation: C797S | Summary: The C797S mutation contributes to tumor development or progression as a resistance mutation in EGFR. Evidence Type: Oncogenic | Mutation: T790M | Summary: The T790M mutation is a resistance mutation that contributes to tumor development or progression in EGFR. Evidence Type: Oncogenic | Mutation: V804M/E | Summary: The V804M/E mutations are identified as gatekeeper mutations that contribute to tumor development or progression in RET. Evidence Type: Oncogenic | Mutation: G810S | Summary: The G810S mutation is a solvent front mutation that contributes to tumor development or progression in RET.

Gene→Variant (gene-first): 1956:C797S 5979:G810S 1956:T790M 5979:V804M/E

Genes: 1956 5979

Variants: C797S G810S T790M V804M/E

[Paragraph-level] PMCID: PMC10524391 Section: RESULTS PassageIndex: 9

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: T790M | Summary: The EGFR T790M mutation is associated with resistance to earlier generation EGFR TKIs, indicating its predictive role in therapy response when patients are treated with osimertinib. Evidence Type: Oncogenic | Mutation: T790M | Summary: The EGFR T790M mutation contributes to tumor progression and is recognized as an oncogenic variant in the context of acquired resistance to EGFR-targeted therapies.

Gene→Variant (gene-first): 1956:T790M

Genes: 1956

Variants: T790M

[Paragraph-level] PMCID: PMC10524391 Section: RESULTS PassageIndex: 8

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: T790M | Summary: The T790M mutation is associated with tumor development and progression, as it is found in a significant proportion of tumors alongside other mutations. Evidence Type: Oncogenic | Mutation: L858R | Summary: The L858R mutation is implicated in tumor development, as it is present in tumors alongside other mutations. Evidence Type: Oncogenic | Mutation: L747S | Summary: The L747S mutation is associated with tumor development, as it is found in a tumor with concurrent mutations.

Gene→Variant (gene-first): 1956:L747S 1956:L858R 1956:T790M

Genes: 1956

Variants: L747S L858R T790M

[Paragraph-level] PMCID: PMC3461408 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: p.His1047Leu | Summary: The p.His1047Leu mutation in PIK3CA is identified as a cancer-associated mutation contributing to tumor development in a patient with a syndrome of congenital overgrowth. Evidence Type: Oncogenic | Mutation: p.His1047Arg | Summary: The p.His1047Arg mutation in PIK3CA is also identified as a cancer-associated mutation found in multiple patients with overlapping syndromes, indicating its role in tumor progression.

Gene→Variant (gene-first): 5290:p.His1047Arg 5290:p.His1047Leu

Genes: 5290

Variants: p.His1047Arg p.His1047Leu

[Paragraph-level] PMCID: PMC1952070 Section: RESULTS PassageIndex: 8

Evidence Type(s): Diagnostic, Predictive

Summary: Evidence Type: Diagnostic | Mutation: G/A; rs10251977 | Summary: The variant rs10251977 is mentioned as a single nucleotide polymorphism, which can be used to classify or define a disease or subtype. Evidence Type: Diagnostic | Mutation: T/C; rs17290643 | Summary: The variant rs17290643 is mentioned as a single nucleotide polymorphism, which can be used to classify or define a disease or subtype. Evidence Type: Predictive | Mutation: G/A; rs10251977 | Summary: There was no correlation between the G/A SNP rs10251977 and gefitinib response, indicating it does not predict therapy response. Evidence Type: Predictive | Mutation: T/C; rs17290643 | Summary: There was no correlation between the T/C SNP rs17290643 and gefitinib response, indicating it does not predict therapy response.

Gene→Variant (gene-first): 7294:G/A NA:rs10251977 NA:rs17290643

Genes: 7294 NA

Variants: G/A rs10251977 rs17290643

[Paragraph-level] PMCID: PMC1952070 Section: RESULTS PassageIndex: 5

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: L858R | Summary: The L858R mutation is associated with a lack of response to gefitinib, indicating its role in predicting treatment resistance. Evidence Type: Predictive | Mutation: T790M | Summary: The T790M mutation is previously documented to confer resistance to gefitinib, supporting its predictive value in treatment response. Evidence Type: Oncogenic | Mutation: L858R | Summary: The L858R mutation is a somatic variant that contributes to tumor development, as it was found in tumor samples and correlates with treatment outcomes. Evidence Type: Oncogenic | Mutation: T790M | Summary: The T790M mutation is a somatic variant that is known to contribute to tumor progression and resistance to therapy.

Gene→Variant (gene-first): 1956:L858R 1956:T790M

Genes: 1956

Variants: L858R T790M

[Paragraph-level] PMCID: PMC5615879 Section: ABSTRACT PassageIndex: 6

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: c.1666C>G | Summary: The mutation p.Q556E (c.1666C>G) is associated with tumor development or progression as part of the KIT mutations observed in the study. Evidence Type: Oncogenic | Mutation: c.1666_1668dupCAG | Summary: The mutation p.Q556dup (c.1666_1668dupCAG) contributes to tumor development or progression, as it is one of the common KIT mutations identified. Evidence Type: Oncogenic | Mutation: c.1672_1677delAAGGTTinsAGT | Summary: The mutation p.K558_V559delinsS (c.1672_1677delAAGGTTinsAGT) is implicated in tumor development or progression, being part of the KIT mutations found in the cases. Evidence Type: Oncogenic | Mutation: c.1509_1510insACCTAT | Summary: The mutation p.Y503_F504insTY (c.1509_1510insACCTAT) is associated with tumor development or progression, as it is one of the identified KIT mutations. Evidence Type: Oncogenic | Mutation: c.1925A>G | Summary: The mutation p.K642R (c.1925A>G) is linked to tumor development or progression, as it is part of the KIT mutations observed in the study.

Gene→Variant (gene-first): 3815:Ala-Tyr 3815:c.1509_1510insACCTAT 728378:c.1666C>G 3815:c.1666_1668dupCAG 3815:c.1672_1677delAAGGTTinsAGT 5156:c.1925A>G 3815:p.K558_V559delinsS 728378:p.K642R 728378:p.Q556E 3815:p.Q556dup 3815:p.Y503_F504insTY

Genes: 3815 728378 5156

Variants: Ala-Tyr c.1509_1510insACCTAT c.1666C>G c.1666_1668dupCAG c.1672_1677delAAGGTTinsAGT c.1925A>G p.K558_V559delinsS p.K642R p.Q556E p.Q556dup p.Y503_F504insTY

[Paragraph-level] PMCID: PMC9365372 Section: ABSTRACT PassageIndex: 9

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: T790M | Summary: The T790M mutation is associated with a favorable clinical response to Abivertinib therapy in patients with NSCLC, indicating its predictive value for treatment efficacy. Evidence Type: Oncogenic | Mutation: T790M | Summary: The T790M mutation contributes to tumor development and progression in non-small cell lung cancer (NSCLC), highlighting its oncogenic role.

Gene→Variant (gene-first): 1956:T790M

Genes: 1956

Variants: T790M

[Paragraph-level] PMCID: PMC9365372 Section: ABSTRACT PassageIndex: 3

Evidence Type(s): Predictive

Summary: Evidence Type: Predictive | Mutation: T790M | Summary: The T790M mutation is associated with resistance to prior EGFR inhibitors and is evaluated for its role in determining the efficacy of abivertinib in patients with non-small cell lung cancer. Evidence Type: Predictive | Mutation: Thr790Met | Summary: The Thr790Met mutation is linked to resistance against previous EGFR inhibitors and is being assessed for its impact on the response to abivertinib in non-small cell lung cancer patients.

Gene→Variant (gene-first): 1956:T790M 1956:Thr790Met

Genes: 1956

Variants: T790M Thr790Met

[Paragraph-level] PMCID: PMC10082285 Section: ABSTRACT PassageIndex: 5

Evidence Type(s): Predictive, Diagnostic

Summary: Evidence Type: Predictive | Mutation: L858R | Summary: The L858R mutation is associated with response to osimertinib therapy in patients with EGFR-mutated NSCLC, indicating its predictive value for treatment sensitivity. Evidence Type: Diagnostic | Mutation: L858R | Summary: The presence of the L858R mutation is used to classify and confirm the diagnosis of EGFR-mutated NSCLC, supporting its role as a diagnostic marker.

Gene→Variant (gene-first): 1956:L858R

Genes: 1956

Variants: L858R

[Paragraph-level] PMCID: PMC9338780 Section: RESULTS PassageIndex: 4

Evidence Type(s): Predictive, Oncogenic, Prognostic

Summary: Evidence Type: Predictive | Mutation: V600E | Summary: The BRAF V600E mutation is associated with a confirmed response to therapy, as evidenced by a high overall response rate (ORR) in patients with this mutation. Evidence Type: Oncogenic | Mutation: V600E | Summary: The BRAF V600E mutation contributes to tumor development or progression, as it is identified in patients with BRAF V600E-mutant disease. Evidence Type: Prognostic | Mutation: V600E | Summary: The presence of the BRAF V600E mutation correlates with disease outcome, as indicated by the median duration of response (DOR) in patients with this mutation.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paragraph-level] PMCID: PMC9338780 Section: RESULTS PassageIndex: 2

Evidence Type(s): Oncogenic, Diagnostic

Summary: Evidence Type: Oncogenic | Mutation: V600E | Summary: The BRAF V600E mutation is confirmed in a significant portion of patients with advanced thyroid cancer, indicating its role in tumor development or progression. Evidence Type: Diagnostic | Mutation: V600E | Summary: The presence of the BRAF V600E mutation is used to confirm the diagnosis of advanced thyroid cancer in the patient cohort.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paragraph-level] PMCID: PMC7294133 Section: ABSTRACT PassageIndex: 2

Evidence Type(s): Oncogenic, Functional, Prognostic, Predictive

Summary: Evidence Type: Oncogenic | Mutation: V871I | Summary: The V871I variant in the EPHB4 gene contributes to tumor development and progression in neuroblastoma by increasing proliferation, migration, and invasion properties in cancer cell lines. Evidence Type: Functional | Mutation: V871I | Summary: The V871I variant alters molecular function by affecting the phosphorylation of the ERK1-2 pathway and influencing the expression of target genes related to cancer progression. Evidence Type: Prognostic | Mutation: V871I | Summary: Higher expression of EPHB4, associated with the V871I variant, correlates with advanced disease stages and poor overall survival in neuroblastoma patients. Evidence Type: Predictive | Mutation: V871I | Summary: The use of EPHB4 inhibitors, which target the effects of the V871I variant, suggests potential therapeutic strategies for neuroblastoma patients.

Gene→Variant (gene-first): 2050:V871I

Genes: 2050

Variants: V871I

[Paragraph-level] PMCID: PMC3266695 Section: ABSTRACT PassageIndex: 2

Evidence Type(s): Predictive, Oncogenic, Functional

Summary: Evidence Type: Predictive | Mutation: V600E | Summary: The BRAF(V600E) mutation is associated with sensitivity to RAF inhibitors in melanoma, indicating its predictive value for therapeutic response. Evidence Type: Oncogenic | Mutation: V600E | Summary: The BRAF(V600E) mutation contributes to tumor development and progression in melanoma, demonstrating its oncogenic potential. Evidence Type: Functional | Mutation: V600E | Summary: The BRAF(V600E) mutation alters the molecular function of the BRAF protein, affecting its dimerization and signaling activity in the context of RAS activation.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paragraph-level] PMCID: PMC2848976 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Predictive, Oncogenic, Functional

Summary: Evidence Type: Predictive | Mutation: BRAFV600E/K | Summary: BRAFV600E/K is targeted for therapy with the specific inhibitor PLX4032, indicating a correlation with treatment response. Evidence Type: Oncogenic | Mutation: BRAFV600E/K | Summary: BRAFV600E/K is described as a mutationally active tumor-specific kinase in melanomas, contributing to tumor development. Evidence Type: Functional | Mutation: Q61L | Summary: The presence of NRAS Q61L mutant primary melanoma cells shows altered cellular behaviors, indicating a change in molecular function. Evidence Type: Predictive | Mutation: Q61L | Summary: PLX4032 increased the rate of proliferation in NRAS Q61L mutant primary melanoma cells, suggesting a correlation with treatment response. Evidence Type: Oncogenic | Mutation: Q61L | Summary: The Q61L mutation in NRAS is associated with advanced lesions and altered cell behavior, contributing to tumor progression.

Gene→Variant (gene-first): 673:BRAFV600E 4893:Q61L 673:V600E/K

Genes: 673 4893

Variants: BRAFV600E Q61L V600E/K

[Paragraph-level] PMCID: PMC2848976 Section: RESULTS PassageIndex: 24

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: BRAFV600E | Summary: The BRAFV600E mutation is associated with a reduction in cell motility in response to PLX4032, indicating a functional impact on the behavior of melanoma cells. Evidence Type: Oncogenic | Mutation: BRAFV600E | Summary: The BRAFV600E mutation contributes to tumor development or progression, as evidenced by its differential response to PLX4032 compared to BRAFWT melanoma cells.

Gene→Variant (gene-first): 673:BRAFV600E

Genes: 673

Variants: BRAFV600E

[Paragraph-level] PMCID: PMC2848976 Section: RESULTS PassageIndex: 23

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: BRAFV600E | Summary: The BRAFV600E mutation is associated with changes in cell adhesion and migration in melanoma cells, indicating its role in tumor development and progression. Evidence Type: Functional | Mutation: BRAFV600E | Summary: The BRAFV600E mutation alters molecular function, as evidenced by the changes in phospho-FAK activation and ERK1/2 phosphorylation in response to treatment.

Gene→Variant (gene-first): 673:BRAFV600E

Genes: 673

Variants: BRAFV600E

[Paragraph-level] PMCID: PMC2848976 Section: RESULTS PassageIndex: 21

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: Q61L | Summary: The NRAS Q61L mutation is associated with tumor development or progression in melanoma, as indicated by its presence in primary melanoma cells. Evidence Type: Functional | Mutation: Q61L | Summary: The Q61L mutation in NRAS may alter molecular or biochemical function, as it is implicated in the activation of signaling pathways in melanoma cells.

Gene→Variant (gene-first): 4893:Q61L

Genes: 4893

Variants: Q61L

[Paragraph-level] PMCID: PMC2848976 Section: RESULTS PassageIndex: 18

Evidence Type(s): Oncogenic, Predictive

Summary: Evidence Type: Oncogenic | Mutation: BRAFV600E | Summary: The BRAFV600E mutation is associated with the lack of activation of IL8 in response to PLX4032 treatment, indicating its role in tumor development or progression. Evidence Type: Predictive | Mutation: BRAFV600E | Summary: The presence of the BRAFV600E mutation correlates with the lack of response to PLX4032 treatment, suggesting its predictive value for therapy resistance.

Gene→Variant (gene-first): 673:BRAFV600E

Genes: 673

Variants: BRAFV600E

[Paragraph-level] PMCID: PMC2848976 Section: RESULTS PassageIndex: 17

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: BRAFV600E | Summary: The BRAFV600E mutation is associated with altered activation of early response genes and contributes to tumor development or progression as indicated by its impact on ERK1/2 functional activation in melanoma cells. Evidence Type: Functional | Mutation: BRAFV600E | Summary: The BRAFV600E mutation alters the molecular function of signaling pathways, as evidenced by the differential activation and downregulation of FOS and JUNB in response to treatment in mutant versus wild-type melanoma cells.

Gene→Variant (gene-first): 673:BRAFV600E

Genes: 673

Variants: BRAFV600E

[Paragraph-level] PMCID: PMC2848976 Section: RESULTS PassageIndex: 16

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: BRAFV600E | Summary: The BRAFV600E mutation is associated with changes in gene expression and activation of downstream ERK targets, indicating an alteration in molecular function related to cellular responses to therapy.

Gene→Variant (gene-first): 673:BRAFV600E

Genes: 673

Variants: BRAFV600E

[Paragraph-level] PMCID: PMC2848976 Section: RESULTS PassageIndex: 13

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: R89L | Summary: The R89L mutation in RAF1 does not bind Ras-GTP, indicating a change in molecular function, as it was activated by PLX4032 similarly to wild-type RAF1.

Gene→Variant (gene-first): 3726:R89L

Genes: 3726

Variants: R89L

[Paragraph-level] PMCID: PMC2848976 Section: RESULTS PassageIndex: 12

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: BRAFV600E | Summary: The BRAFV600E mutation is associated with non-detectable activity in certain cell lines, indicating its role in tumor development or progression. Evidence Type: Oncogenic | Mutation: BRAFV600K | Summary: The BRAFV600K mutation is associated with non-detectable activity in certain cell lines, indicating its role in tumor development or progression.

Gene→Variant (gene-first): 673:BRAFV600E 673:BRAFV600K

Genes: 673

Variants: BRAFV600E BRAFV600K

[Paragraph-level] PMCID: PMC2848976 Section: RESULTS PassageIndex: 11

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: BRAFV600E | Summary: The BRAFV600E mutation is associated with high enzymatic activity, indicating that it alters molecular function. Evidence Type: Functional | Mutation: BRAFV600K | Summary: The BRAFV600K mutation is associated with high enzymatic activity, indicating that it alters molecular function.

Gene→Variant (gene-first): 673:BRAFV600E 673:BRAFV600K

Genes: 673

Variants: BRAFV600E BRAFV600K

[Paragraph-level] PMCID: PMC2848976 Section: RESULTS PassageIndex: 8

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: BRAFV600E | Summary: The passage discusses the effects of the BRAFV600E mutation on intracellular signaling pathways, indicating that it alters the molecular function related to the response to PLX4032 treatment.

Gene→Variant (gene-first): 673:BRAFV600E

Genes: 673

Variants: BRAFV600E

[Paragraph-level] PMCID: PMC2848976 Section: RESULTS PassageIndex: 7

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: BRAFV600E | Summary: The BRAFV600E mutation is associated with a response to the drug PLX4032, indicating its predictive value for therapy sensitivity. Evidence Type: Oncogenic | Mutation: BRAFV600E | Summary: The BRAFV600E mutation contributes to tumor development or progression, as evidenced by its role in melanoma cells.

Gene→Variant (gene-first): 673:BRAFV600E

Genes: 673

Variants: BRAFV600E

[Paragraph-level] PMCID: PMC2848976 Section: RESULTS PassageIndex: 6

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: BRAFV600E | Summary: The BRAFV600E mutation is associated with changes in the phosphorylation state of ERK1/2, indicating an alteration in molecular function related to signaling pathways in melanoma cells. Evidence Type: Oncogenic | Mutation: BRAFV600E | Summary: The BRAFV600E mutation contributes to tumor development or progression in melanoma, as evidenced by its presence in specific melanoma cell lines and its impact on ERK signaling.

Gene→Variant (gene-first): 673:BRAFV600E

Genes: 673

Variants: BRAFV600E

[Paragraph-level] PMCID: PMC2848976 Section: RESULTS PassageIndex: 5

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: BRAFV600E | Summary: The BRAFV600E mutation correlates with the response to the therapy PLX4032, as it abolishes ERK1/2 activating phosphorylation in melanoma cells. Evidence Type: Predictive | Mutation: BRAFV600K | Summary: The BRAFV600K mutation also correlates with the response to PLX4032, as it shows a similar pattern of ERK1/2 phosphorylation in response to the drug. Evidence Type: Oncogenic | Mutation: BRAFV600E | Summary: The BRAFV600E mutation contributes to tumor development or progression, as indicated by its role in melanoma cells. Evidence Type: Oncogenic | Mutation: BRAFV600K | Summary: The BRAFV600K mutation contributes to tumor development or progression, as indicated by its role in melanoma cells.

Gene→Variant (gene-first): 673:BRAFV600K 673:V600E/K

Genes: 673

Variants: BRAFV600K V600E/K

[Paragraph-level] PMCID: PMC2848976 Section: RESULTS PassageIndex: 3

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: V600E | Summary: The V600E mutation in BRAF is associated with sensitivity to the therapy PLX4032, indicating a predictive relationship between the mutation and treatment response. Evidence Type: Oncogenic | Mutation: V600E | Summary: The V600E mutation in BRAF contributes to tumor development and progression in melanoma, supporting its classification as an oncogenic variant.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paragraph-level] PMCID: PMC2670982 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Predisposing, Oncogenic, Functional

Summary: Evidence Type: Predisposing | Mutation: R849W | Summary: The R849W mutation is described as an inherited variant associated with a rare form of venous anomalies, indicating it confers inherited risk for disease. Evidence Type: Oncogenic | Mutation: L914F | Summary: The L914F mutation is identified as a somatic variant contributing to tumor development, as it is associated with loss-of-function of the TIE2 receptor in a resected venous malformation. Evidence Type: Functional | Mutation: L914F | Summary: The L914F mutation alters molecular function, as it shows ligand-independent hyperphosphorylation and abnormal localization in endothelial cells when overexpressed.

Gene→Variant (gene-first): 284:L914F 7010:R849W

Genes: 284 7010

Variants: L914F R849W

[Paragraph-level] PMCID: PMC2830973 Section: RESULTS PassageIndex: 12

Evidence Type(s): None

Summary: Not enough information in this passage.

Gene→Variant (gene-first): 207:serine/threonine

Genes: 207

Variants: serine/threonine

[Paragraph-level] PMCID: PMC2830973 Section: RESULTS PassageIndex: 6

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: V674A | Summary: The JAK3 V674A mutation is identified as an activating allele that can transform pro-B cells to IL-3-independent growth, indicating its role in tumor development. Evidence Type: Functional | Mutation: V674A | Summary: The JAK3 V674A variant alters the molecular function of JAK3, leading to persistent activation and IL-3-independent growth in BaF3 cells.

Gene→Variant (gene-first): 3718:V674A

Genes: 3718

Variants: V674A

[Paragraph-level] PMCID: PMC5491373 Section: RESULTS PassageIndex: 31

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: K13 | Summary: The substitution of K13 to arginine alters the molecular function of PTEN, blocking its redistribution to the nucleus.

Gene→Variant (gene-first): 2597:K13

Genes: 2597

Variants: K13

[Paragraph-level] PMCID: PMC5491373 Section: RESULTS PassageIndex: 30

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: K48R | Summary: The K48R mutation alters the molecular function of ubiquitin, affecting the localization and abundance of PTENL320S-GFP, indicating its role in nuclear accumulation and degradation processes.

Gene→Variant (gene-first): 5728:K48R

Genes: 5728

Variants: K48R

[Paragraph-level] PMCID: PMC5491373 Section: RESULTS PassageIndex: 29

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: Lys48 | Summary: The mutation Lys48 is involved in the formation of polyubiquitin chains, and its alteration affects the molecular function related to nuclear localization of the PTENL320S variant.

Gene→Variant (gene-first): 5728:Lys48

Genes: 5728

Variants: Lys48

[Paragraph-level] PMCID: PMC5491373 Section: RESULTS PassageIndex: 26

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: T277A | Summary: The T277A mutation alters the ability of the membrane-binding regulatory interface to interact with the C-terminal tail of PTEN, indicating a change in molecular function. Evidence Type: Functional | Mutation: L320S | Summary: The L320S mutation also affects the interaction between the membrane-binding regulatory interface and the C-terminal tail of PTEN, suggesting a modification in molecular function.

Gene→Variant (gene-first): 4734:L320S 5728:T277A

Genes: 4734 5728

Variants: L320S T277A

[Paragraph-level] PMCID: PMC5491373 Section: RESULTS PassageIndex: 25

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: L320S | Summary: The L320S mutation alters molecular function by inhibiting the interaction between the membrane-bound regulatory interface and the C-terminus. Evidence Type: Functional | Mutation: T277A | Summary: The T277A mutation alters molecular function by inhibiting the interaction between the membrane-bound regulatory interface and the C-terminus.

Gene→Variant (gene-first): 4734:L320S

Genes: 4734

Variants: L320S

[Paragraph-level] PMCID: PMC5491373 Section: RESULTS PassageIndex: 24

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: T277A | Summary: The T277A mutation alters the ubiquitination of PTEN, indicating a change in molecular function related to protein stability. Evidence Type: Functional | Mutation: L320S | Summary: The L320S mutation also affects the ubiquitination of PTEN, suggesting a modification in molecular function that impacts protein stability.

Gene→Variant (gene-first): 4734:L320S 5728:T277A

Genes: 4734 5728

Variants: L320S T277A

[Paragraph-level] PMCID: PMC5491373 Section: RESULTS PassageIndex: 23

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: L320S | Summary: The L320S mutation alters the protein conformation and folding of PTEN, as evidenced by its susceptibility to trypsin digestion compared to wild-type PTEN. Evidence Type: Functional | Mutation: T277A | Summary: The T277A mutation affects the protein conformation and folding of PTEN, demonstrated by its lower half-lives during trypsin digestion relative to wild-type PTEN.

Gene→Variant (gene-first): 4734:L320S 5728:T277A

Genes: 4734 5728

Variants: L320S T277A

[Paragraph-level] PMCID: PMC5491373 Section: RESULTS PassageIndex: 22

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: F273 | Summary: The F273 mutation is suggested to alter the molecular function of PTEN by affecting its conformation and localization. Evidence Type: Functional | Mutation: F273A | Summary: The F273A mutation shows altered inhibition on nuclear accumulation and membrane localization, indicating a change in molecular function. Evidence Type: Functional | Mutation: F273L | Summary: The F273L mutation is involved in restoring the localization of PTEN, suggesting it impacts the molecular function of the protein. Evidence Type: Functional | Mutation: L320 | Summary: The L320 mutation is implicated in maintaining PTEN conformation necessary for its localization, indicating a functional role. Evidence Type: Functional | Mutation: L320S | Summary: The L320S mutation shows altered inhibition similar to F273A, suggesting it affects the molecular function of PTEN. Evidence Type: Functional | Mutation: L320F | Summary: The L320F mutation is involved in restoring PTEN localization, indicating a change in its molecular function.

Gene→Variant (gene-first): 5295:F273 5295:F273A 5295:F273L 4734:L320 4734:L320F 4734:L320S

Genes: 5295 4734

Variants: F273 F273A F273L L320 L320F L320S

[Paragraph-level] PMCID: PMC5491373 Section: RESULTS PassageIndex: 21

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: T277A | Summary: The T277A mutation alters the molecular conformation of PTEN, promoting its ubiquitination. Evidence Type: Functional | Mutation: L320S | Summary: The L320S mutation also affects the conformation of PTEN, leading to increased ubiquitination.

Gene→Variant (gene-first): 4734:L320S 5728:T277A

Genes: 4734 5728

Variants: L320S T277A

[Paragraph-level] PMCID: PMC5491373 Section: RESULTS PassageIndex: 20

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: L320S | Summary: The L320S mutation affects phosphorylation at other sites on PTEN, indicating a potential alteration in molecular function. Evidence Type: Functional | Mutation: T319 | Summary: The T319 residue is involved in phosphorylation by ROCK, suggesting it plays a role in the molecular function of PTEN. Evidence Type: Functional | Mutation: T319A | Summary: The T319A mutation does not enhance protein stability, indicating an alteration in the molecular function of PTEN. Evidence Type: Functional | Mutation: T321 | Summary: The T321 residue is involved in phosphorylation by ROCK, suggesting it plays a role in the molecular function of PTEN. Evidence Type: Functional | Mutation: T321A | Summary: The T321A mutation does not enhance protein stability, indicating an alteration in the molecular function of PTEN.

Gene→Variant (gene-first): 4734:L320S 5728:T319 5728:T319A 5728:T321 5728:T321A

Genes: 4734 5728

Variants: L320S T319 T319A T321 T321A

[Paragraph-level] PMCID: PMC5491373 Section: RESULTS PassageIndex: 19

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: L320S | Summary: The substitution of L320 to S alters the molecular function of PTEN by creating a new potential phosphorylation site, which affects its stability and localization. Evidence Type: Functional | Mutation: L320A | Summary: The introduction of L320A into PTENA4 does not affect the strong inhibition of membrane and nuclear localization, indicating a functional role in PTEN's behavior. Evidence Type: Functional | Mutation: L320D | Summary: The phospho-mimetic mutation L320D does not show instabilities similar to those seen in PTENL320S, suggesting a functional difference in protein behavior. Evidence Type: Functional | Mutation: L320E | Summary: Similar to L320D, the phospho-mimetic mutation L320E does not exhibit instabilities like PTENL320S, indicating its functional impact on PTEN.

Gene→Variant (gene-first): 4734:L320 4734:L320A 4734:L320D 4734:L320E 4734:L320S

Genes: 4734

Variants: L320 L320A L320D L320E L320S

[Paragraph-level] PMCID: PMC5491373 Section: RESULTS PassageIndex: 16

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: T277A | Summary: The T277A mutation alters PTEN's ability to localize to the plasma membrane, resulting in its retention in the cytosol and affecting its function in reducing AKT phosphorylation. Evidence Type: Functional | Mutation: L320S | Summary: The L320S mutation similarly inhibits PTEN's membrane localization, leading to its accumulation in the cytosol and potentially impacting its role in tumor suppression. Evidence Type: Functional | Mutation: K13R | Summary: The K13R mutation is involved in the context of PTEN localization studies, but specific functional impacts are not detailed in the passage.

Gene→Variant (gene-first): 2597:K13R 4734:L320S 5728:T277A

Genes: 2597 4734 5728

Variants: K13R L320S T277A

[Paragraph-level] PMCID: PMC5491373 Section: RESULTS PassageIndex: 15

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: L320S | Summary: The L320S mutation alters the molecular function by blocking PTEN membrane and nuclear localization. Evidence Type: Functional | Mutation: T277A | Summary: The T277A mutation alters the molecular function by blocking PTEN membrane and nuclear localization.

Gene→Variant (gene-first): 4734:L320S 5728:T277A

Genes: 4734 5728

Variants: L320S T277A

[Paragraph-level] PMCID: PMC5491373 Section: RESULTS PassageIndex: 12

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: L320S | Summary: The L320S mutation is associated with altered stability of the PTEN protein, indicating a change in molecular function. Evidence Type: Functional | Mutation: T366 | Summary: Phosphorylation at T366 is shown to destabilize the PTEN protein, suggesting a functional impact on its molecular behavior. Evidence Type: Functional | Mutation: S370 | Summary: Phosphorylation at S370 contributes to the destabilization of the PTEN protein, indicating a change in its molecular function. Evidence Type: Functional | Mutation: T366A | Summary: The T366A mutation is part of constructs that were tested for stability, indicating its role in altering the molecular function of PTEN. Evidence Type: Functional | Mutation: S370A | Summary: The S370A mutation is included in constructs that failed to stabilize PTEN, suggesting an impact on its molecular function.

Gene→Variant (gene-first): 4734:L320S 5728:S370 5728:S370A 5728:T366 5728:T366A

Genes: 4734 5728

Variants: L320S S370 S370A T366 T366A

[Paragraph-level] PMCID: PMC5491373 Section: RESULTS PassageIndex: 11

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: L320S | Summary: The L320S mutation decreases the stability of PTEN and alters its interactions with the plasma membrane, indicating a change in molecular function. Evidence Type: Functional | Mutation: K13 | Summary: The K13 mutation is involved in blocking ubiquitination, which affects PTEN stability and its degradation process, suggesting a functional alteration. Evidence Type: Functional | Mutation: K13R | Summary: The K13R mutation blocks ubiquitination at K13, impacting PTEN stability and its biochemical function. Evidence Type: Functional | Mutation: C124S | Summary: The C124S mutation stabilizes PTEN by presumably inhibiting its enzymatic activity, indicating a change in molecular function.

Gene→Variant (gene-first): 5728:C124S 2597:K13 2597:K13R 4734:L320S

Genes: 5728 2597 4734

Variants: C124S K13 K13R L320S

[Paragraph-level] PMCID: PMC5491373 Section: RESULTS PassageIndex: 8

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: L320S | Summary: The PTENL320S variant shows decreased activity to suppress AKT phosphorylation, indicating an alteration in molecular function. Evidence Type: Functional | Mutation: T277A | Summary: The PTENT277A variant also demonstrates decreased activity to suppress AKT phosphorylation, suggesting a change in molecular function.

Gene→Variant (gene-first): 4734:L320S 5728:T277A

Genes: 4734 5728

Variants: L320S T277A

[Paragraph-level] PMCID: PMC5491373 Section: RESULTS PassageIndex: 6

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: L320S | Summary: The L320S mutation was tested for its effect on enzymatic activity, showing lipid phosphatase activity indistinguishable from wild-type PTEN, indicating it does not alter molecular function. Evidence Type: Functional | Mutation: T277A | Summary: The T277A mutation was also tested for its effect on enzymatic activity, demonstrating lipid phosphatase activity similar to wild-type PTEN, suggesting it does not alter molecular function.

Gene→Variant (gene-first): 4734:L320S 5728:T277A

Genes: 4734 5728

Variants: L320S T277A

[Paragraph-level] PMCID: PMC5491373 Section: RESULTS PassageIndex: 4

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: L320S | Summary: The L320S mutation alters the molecular function of the PTEN protein, as it is associated with decreased steady state levels and affects PTEN localization. Evidence Type: Functional | Mutation: T277A | Summary: The T277A mutation also alters the molecular function of the PTEN protein, leading to decreased steady state levels and impacting PTEN localization.

Gene→Variant (gene-first): 4734:L320S 5728:T277A

Genes: 4734 5728

Variants: L320S T277A

[Paragraph-level] PMCID: PMC4845427 Section: RESULTS PassageIndex: 29

Evidence Type(s): None

Summary: Not enough information in this passage.

Gene→Variant (gene-first): 861:A to I

Genes: 861

Variants: A to I

[Paragraph-level] PMCID: PMC4845427 Section: RESULTS PassageIndex: 3

Evidence Type(s): Predisposing

Summary: Evidence Type: Predisposing | Mutation: A to I | Summary: The passage indicates that the RUNX1 alterations are germline, suggesting they confer inherited risk for disease in the identified pedigrees.

Gene→Variant (gene-first): 861:A to I

Genes: 861

Variants: A to I

[Paragraph-level] PMCID: PMC3483540 Section: RESULTS PassageIndex: 12

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: C > A | Summary: The C > A transversion is identified as a more frequent somatic mutation in lung cancers of smokers, suggesting its contribution to tumor development or progression. Evidence Type: Oncogenic | Mutation: T > G | Summary: The T > G transversion is noted as a more common somatic mutation in lung cancers of never-smokers, indicating its potential role in tumor development or progression.

Gene→Variant (gene-first): 2199:C > A 2199:T > G

Genes: 2199

Variants: C > A T > G

[Paragraph-level] PMCID: PMC3483540 Section: RESULTS PassageIndex: 5

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: L858R | Summary: The L858R mutation in EGFR is identified as a driver mutation contributing to lung adenocarcinoma. Evidence Type: Oncogenic | Mutation: G719A | Summary: The G719A mutation in EGFR is recognized as a driver mutation associated with lung adenocarcinoma. Evidence Type: Oncogenic | Mutation: G12C | Summary: The G12C mutation in KRAS is classified as a driver mutation that contributes to lung cancer. Evidence Type: Oncogenic | Mutation: G12V | Summary: The G12V mutation in KRAS is identified as a driver mutation involved in lung cancer development. Evidence Type: Oncogenic | Mutation: G12D | Summary: The G12D mutation in KRAS is recognized as a driver mutation contributing to lung cancer. Evidence Type: Oncogenic | Mutation: G12S | Summary: The G12S mutation in KRAS is classified as a driver mutation associated with lung cancer. Evidence Type: Oncogenic | Mutation: G13C | Summary: The G13C mutation in KRAS is identified as a driver mutation contributing to lung cancer. Evidence Type: Oncogenic | Mutation: G13D | Summary: The G13D mutation in KRAS is recognized as a driver mutation involved in lung cancer. Evidence Type: Oncogenic | Mutation: Q61H | Summary: The Q61H mutation in NRAS is classified as a driver mutation associated with lung cancer. Evidence Type: Oncogenic | Mutation: Q61L | Summary: The Q61L mutation in NRAS is identified as a driver mutation contributing to lung cancer. Evidence Type: Oncogenic | Mutation: Q61K | Summary: The Q61K mutation in NRAS is recognized as a driver mutation involved in lung cancer. Evidence Type: Oncogenic | Mutation: H1047R | Summary: The H1047R mutation in PIK3CA is classified as a driver mutation associated with lung cancer. Evidence Type: Oncogenic | Mutation: E555K | Summary: The E555K mutation in PIK3CA is identified as a driver mutation contributing to lung cancer. Evidence Type: Oncogenic | Mutation: V600E | Summary: The V600E mutation in BRAF is recognized as a driver mutation involved in lung cancer. Evidence Type: Oncogenic | Mutation: D32G | Summary: The D32G mutation in CTNNB1 is classified as a driver mutation associated with lung adenocarcinoma. Evidence Type: Oncogenic | Mutation: M1124D | Summary: The M1124D mutation in MET is identified as a driver mutation contributing to lung adenocarcinoma.

Gene→Variant (gene-first): 1499:D32G 22853:E555K 3845:G12C 3845:G12D 3845:G12S 3845:G12V 3845:G13C 3845:G13D 1956:G719A 5290:H1047R 1956:L858R 1499:M1124D 3845:Q61H 4893:Q61K 4893:Q61L 673:V600E

Genes: 1499 22853 3845 1956 5290 4893 673

Variants: D32G E555K G12C G12D G12S G12V G13C G13D G719A H1047R L858R M1124D Q61H Q61K Q61L V600E

[Paragraph-level] PMCID: PMC5629366 Section: RESULTS PassageIndex: 18

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: R132H | Summary: The R132H mutation in IDH1 is associated with treatment response to BAY1436032, indicating a correlation with sensitivity to this specific therapy. Evidence Type: Oncogenic | Mutation: R132H | Summary: The R132H mutation contributes to tumor development or progression in human AML cells, as indicated by its presence in the context of IDH1/IDH2 mutations.

Gene→Variant (gene-first): 3417:R132H

Genes: 3417

Variants: R132H

[Paragraph-level] PMCID: PMC5629366 Section: RESULTS PassageIndex: 17

Evidence Type(s): Predictive, Functional

Summary: Evidence Type: Predictive | Mutation: R132H | Summary: The R132H mutation in IDH1 is associated with sensitivity to the treatment with BAY1436032, indicating a correlation with therapeutic response in AML cells. Evidence Type: Functional | Mutation: R132H | Summary: The R132H mutation alters the histone methylation phenotype in AML cells, demonstrating a change in molecular function related to histone trimethylation levels.

Gene→Variant (gene-first): 3417:R132H

Genes: 3417

Variants: R132H

[Paragraph-level] PMCID: PMC5629366 Section: RESULTS PassageIndex: 7

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: p.D835del | Summary: The p.D835del mutation in FLT3-TKD is associated with tumor development in acute myeloid leukemia (AML) as indicated by its presence in primary AML cells. Evidence Type: Oncogenic | Mutation: p.Q61R | Summary: The p.Q61R mutation in NRAS is implicated in tumor progression in acute myeloid leukemia (AML) as it was identified as an additional aberration in the patient’s AML cells.

Gene→Variant (gene-first): 2322:p.D835del 4893:p.Q61R

Genes: 2322 4893

Variants: p.D835del p.Q61R

[Paragraph-level] PMCID: PMC5629366 Section: RESULTS PassageIndex: 3

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: R132C | Summary: The R132C mutation in IDH1 is associated with sensitivity to the IDH1 inhibitor BAY1436032, indicating a predictive relationship for therapy response. Evidence Type: Predictive | Mutation: R132G | Summary: The R132G mutation in IDH1 shows sensitivity to the IDH1 inhibitor BAY1436032, suggesting it is predictive of treatment response. Evidence Type: Predictive | Mutation: R132H | Summary: The R132H mutation in IDH1 correlates with sensitivity to the IDH1 inhibitor BAY1436032, indicating a predictive relationship for therapy response. Evidence Type: Predictive | Mutation: R132L | Summary: The R132L mutation in IDH1 is linked to sensitivity to the IDH1 inhibitor BAY1436032, suggesting a predictive relationship for treatment response. Evidence Type: Predictive | Mutation: R132S | Summary: The R132S mutation in IDH1 is associated with sensitivity to the IDH1 inhibitor BAY1436032, indicating a predictive relationship for therapy response. Evidence Type: Oncogenic | Mutation: R132C | Summary: The R132C mutation in IDH1 contributes to tumor development, supporting its classification as an oncogenic variant. Evidence Type: Oncogenic | Mutation: R132G | Summary: The R132G mutation in IDH1 is implicated in tumor development, supporting its classification as an oncogenic variant. Evidence Type: Oncogenic | Mutation: R132H | Summary: The R132H mutation in IDH1 is associated with tumor development, indicating its oncogenic potential. Evidence Type: Oncogenic | Mutation: R132L | Summary: The R132L mutation in IDH1 contributes to tumor development, supporting its classification as an oncogenic variant. Evidence Type: Oncogenic | Mutation: R132S | Summary: The R132S mutation in IDH1 is implicated in tumor development, indicating its oncogenic potential.

Gene→Variant (gene-first): 3417:R132C 3417:R132G 3417:R132H 3417:R132L 3417:R132S 3418:R140Q

Genes: 3417 3418

Variants: R132C R132G R132H R132L R132S R140Q

[Paragraph-level] PMCID: PMC3973211 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Prognostic, Functional, Oncogenic

Summary: Evidence Type: Prognostic | Mutation: Arg248 | Summary: The Arg248 mutation is associated with shorter patient survival, indicating its prognostic significance in human cancers. Evidence Type: Prognostic | Mutation: Arg282 | Summary: The Arg282 mutation is linked to shorter patient survival, highlighting its prognostic relevance in cancer outcomes. Evidence Type: Functional | Mutation: R282W | Summary: The R282W mutation significantly upregulates CYP3A4 mRNA and protein levels, indicating an alteration in molecular function related to drug metabolism. Evidence Type: Oncogenic | Mutation: R282W | Summary: The R282W mutation contributes to tumor development by displaying higher expression and resistance to chemotherapeutic drugs, demonstrating its oncogenic potential.

Gene→Variant (gene-first): 7157:Arg248 7157:Arg282 7157:R282W

Genes: 7157

Variants: Arg248 Arg282 R282W

[Paragraph-level] PMCID: PMC4234187 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: C118S | Summary: The C118S mutation in the Kras gene is investigated for its role in tumorigenesis, showing that it impedes urethane-induced lung tumor development, indicating its contribution to cancer progression. Evidence Type: Functional | Mutation: C118S | Summary: The C118S mutation alters the molecular function of the Kras protein, as it affects the activation and subsequent tumorigenic potential in response to carcinogen exposure.

Gene→Variant (gene-first): 4843:C118 4843:C118S 4843:cysteine 118

Genes: 4843

Variants: C118 C118S cysteine 118

[Paragraph-level] PMCID: PMC8040738 Section: RESULTS PassageIndex: 3

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: p.T599dup BRAF | Summary: The p.T599dup BRAF variant is associated with tumor development or progression, as indicated by its presence in tumor-extracted DNA from the patient's resection. Evidence Type: Functional | Mutation: p.T599dup BRAF | Summary: The p.T599dup BRAF variant alters molecular or biochemical function, as it was detected through deep, targeted sequencing of tumor DNA.

Gene→Variant (gene-first): NA:p.T599dup BRAF

Genes: NA

Variants: p.T599dup BRAF

[Paragraph-level] PMCID: PMC8040738 Section: RESULTS PassageIndex: 2

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: p.T599dup | Summary: The BRAF p.T599dup mutation was identified in a low-grade glioma, indicating its contribution to tumor development or progression. Evidence Type: Functional | Mutation: p.T599dup | Summary: The BRAF p.T599dup mutation is likely to alter molecular or biochemical function, as it is associated with a specific tumor type.

Gene→Variant (gene-first): 673:p.T599dup

Genes: 673

Variants: p.T599dup

[Paragraph-level] PMCID: PMC5873857 Section: RESULTS PassageIndex: 6

Evidence Type(s): Oncogenic, Predictive

Summary: Evidence Type: Oncogenic | Mutation: BRAFV600E | Summary: The BRAFV600E mutation contributes to tumor development by leading to disordered vessel formation and impaired blood flow in zebrafish models, recapitulating clinical features of vascular malformations. Evidence Type: Predictive | Mutation: BRAFV600E | Summary: The BRAFV600E mutation correlates with response to vemurafenib treatment, an approved BRAF inhibitor, as zebrafish with this mutation exhibited improved blood flow following therapy.

Gene→Variant (gene-first): 673:BRAFV600E

Genes: 673

Variants: BRAFV600E

[Paragraph-level] PMCID: PMC5873857 Section: RESULTS PassageIndex: 4

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: E62del | Summary: The deletion of residues 58-62 (E62del) is predicted to affect the integrity of helix A, indicating an alteration in molecular function. Evidence Type: Functional | Mutation: K57 | Summary: K57 is identified as a critical amino acid involved in a hydrogen bond interaction, suggesting its role in the molecular function of the protein. Evidence Type: Functional | Mutation: c.159_173del | Summary: The novel deletion c.159_173del is predicted to affect the integrity of helix A, indicating an alteration in molecular function. Evidence Type: Functional | Mutation: c.173_187del | Summary: The deletion c.173_187del is predicted to affect the integrity of helix A, indicating an alteration in molecular function. Evidence Type: Functional | Mutation: p.[K57N] | Summary: The missense variant p.[K57N] is associated with critical interactions in the protein structure, suggesting an alteration in molecular function.

Gene→Variant (gene-first): 5604:E62del NA:K57 5604:c.159_173del 5604:c.173_187del 5604:p.[K57N]

Genes: 5604 NA

Variants: E62del K57 c.159_173del c.173_187del p.[K57N]

[Paragraph-level] PMCID: PMC5873857 Section: RESULTS PassageIndex: 2

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: c.159_173del | Summary: The variant c.159_173del is part of a cluster of pathogenic variants identified in MAP2K1, contributing to the development of arteriovenous malformations (AVMs) and indicating its role in tumor progression within the RAS/MAPK signaling pathway. Evidence Type: Functional | Mutation: c.159_173del | Summary: The c.159_173del variant alters the molecular function of the MAP2K1 gene, which is implicated in the RAS/MAPK signaling pathway, suggesting a biochemical impact relevant to the clinical phenotype observed in patients with AVMs.

Gene→Variant (gene-first): 5604:c.159_173del

Genes: 5604

Variants: c.159_173del

[Paragraph-level] PMCID: PMC7068240 Section: RESULTS PassageIndex: 11

Evidence Type(s): Prognostic

Summary: Evidence Type: Prognostic | Mutation: V600E | Summary: The presence of the BRAF V600E mutation correlates with poorer outcomes in patients with stage IV colorectal cancer, indicating its prognostic significance.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paragraph-level] PMCID: PMC7068240 Section: RESULTS PassageIndex: 4

Evidence Type(s): Oncogenic, Prognostic

Summary: Evidence Type: Oncogenic | Mutation: V600E | Summary: The BRAF V600E mutation is associated with non-MSI tumors and contributes to tumor development or progression in colorectal cancer. Evidence Type: Prognostic | Mutation: V600E | Summary: The presence of the BRAF V600E mutation correlates with the expression of specific miRNAs, indicating its potential as a prognostic biomarker in colorectal cancer.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paragraph-level] PMCID: PMC7068240 Section: RESULTS PassageIndex: 3

Evidence Type(s): Oncogenic, Diagnostic

Summary: Evidence Type: Oncogenic | Mutation: V600E | Summary: The BRAF V600E mutation is associated with tumor development or progression in colorectal cancer (CRC) specimens, indicating its role as an oncogenic variant. Evidence Type: Diagnostic | Mutation: V600E | Summary: The presence of the BRAF V600E mutation is used to classify and define subtypes of colorectal cancer based on their mutational profiles and MSI status.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paragraph-level] PMCID: PMC7068240 Section: RESULTS PassageIndex: 2

Evidence Type(s): Diagnostic, Oncogenic

Summary: Evidence Type: Diagnostic | Mutation: V600E | Summary: The BRAF V600E mutation is associated with colorectal cancers (CRCs), indicating its role in defining or classifying this subtype of cancer. Evidence Type: Oncogenic | Mutation: V600E | Summary: The BRAF V600E mutation contributes to tumor development or progression in colorectal cancers.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paragraph-level] PMCID: PMC5083195 Section: RESULTS PassageIndex: 16

Evidence Type(s): Predictive, Functional

Summary: Evidence Type: Predictive | Mutation: rs1122269 | Summary: The SNP rs1122269 in the CDH4 gene correlates with the response to gemcitabine treatment, indicating its potential as a predictive biomarker for therapy response. Evidence Type: Functional | Mutation: rs1122269 | Summary: The variant rs1122269 affects CDH4 expression levels in lymphoblastoid cell lines after exposure to gemcitabine, demonstrating a functional impact on molecular expression.

Gene→Variant (gene-first): 1002:rs1122269

Genes: 1002

Variants: rs1122269

[Paragraph-level] PMCID: PMC5083195 Section: RESULTS PassageIndex: 12

Evidence Type(s): Functional, Prognostic

Summary: Evidence Type: Functional | Mutation: rs1122269 | Summary: The variant rs1122269 showed negative correlations with the expression of CDH4 in a cis-manner, indicating it may alter molecular function related to gene expression. Evidence Type: Functional | Mutation: rs4925193 | Summary: The variant rs4925193 also demonstrated negative correlations with the expression of CDH4 in a cis-manner, suggesting it may influence molecular function associated with gene expression. Evidence Type: Prognostic | Mutation: rs1122269 | Summary: The mRNA expression levels of CDH4, associated with variant rs1122269, correlated with overall survival (OS) in pancreatic cancer patients, indicating a potential prognostic role. Evidence Type: Prognostic | Mutation: rs4925193 | Summary: The mRNA expression levels of CDH4, associated with variant rs4925193, correlated with overall survival (OS) in pancreatic cancer patients, suggesting a potential prognostic significance.

Gene→Variant (gene-first): 1002:rs1122269 1002:rs4925193 NA:rs9637468

Genes: 1002 NA

Variants: rs1122269 rs4925193 rs9637468

[Paragraph-level] PMCID: PMC5083195 Section: RESULTS PassageIndex: 10

Evidence Type(s): Predictive

Summary: Evidence Type: Predictive | Mutation: rs9637468 | Summary: The variant rs9637468 is associated with gemcitabine response during pancreatic cancer therapy, indicating its potential as a genetic biomarker for predicting treatment outcomes. Evidence Type: Predictive | Mutation: rs4925193 | Summary: The variant rs4925193 is associated with gemcitabine response during pancreatic cancer therapy, suggesting its role as a genetic biomarker for predicting treatment outcomes.

Gene→Variant (gene-first): 1002:rs4925193 NA:rs9637468

Genes: 1002 NA

Variants: rs4925193 rs9637468

[Paragraph-level] PMCID: PMC5083195 Section: RESULTS PassageIndex: 7

Evidence Type(s): Predictive

Summary: Evidence Type: Predictive | Mutation: rs7515290 | Summary: The SNP rs7515290 showed trends associated with gemcitabine IC50 values, indicating a potential correlation with drug response in pancreatic cancer. Evidence Type: Predictive | Mutation: rs1374679 | Summary: The SNP rs1374679 demonstrated trends associated with gemcitabine IC50 values, suggesting a possible link to drug response in pancreatic cancer. Evidence Type: Predictive | Mutation: rs10979372 | Summary: The SNP rs10979372 was associated with gemcitabine IC50 values, indicating its potential role in influencing drug response in pancreatic cancer. Evidence Type: Predictive | Mutation: rs1122269 | Summary: The SNP rs1122269 showed trends related to gemcitabine IC50 values, implying a potential impact on drug response in pancreatic cancer.

Gene→Variant (gene-first): NA:rs10979372 1002:rs1122269 NA:rs1374679 57554:rs7515290

Genes: NA 1002 57554

Variants: rs10979372 rs1122269 rs1374679 rs7515290

[Paragraph-level] PMCID: PMC6333965 Section: RESULTS PassageIndex: 12

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: E545K | Summary: The PIK3CA E545K missense mutation is established as a canonical mutation contributing to tumor development. Evidence Type: Oncogenic | Mutation: R58X | Summary: The CDKN2A R58X nonsense mutation is associated with tumor development due to its role in cell cycle regulation. Evidence Type: Oncogenic | Mutation: R209Q/W | Summary: The TP53 inactivating mutations R209Q/W are implicated in cell cycle deregulation, contributing to tumor progression. Evidence Type: Oncogenic | Mutation: R243W/Q | Summary: The TP53 inactivating mutations R243W/Q are associated with cell cycle deregulation, indicating their role in tumor development.

Gene→Variant (gene-first): 5290:E545K 7157:R209Q/W 7157:R243W/Q 1029:R58X

Genes: 5290 7157 1029

Variants: E545K R209Q/W R243W/Q R58X

[Paragraph-level] PMCID: PMC3997489 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Oncogenic, Diagnostic

Summary: Evidence Type: Oncogenic | Mutation: K27M | Summary: The K27M mutation is associated with the development and progression of Diffuse Intrinsic Pontine Glioma (DIPG), contributing to the tumor's oncogenic characteristics. Evidence Type: Diagnostic | Mutation: K27M | Summary: The presence of the K27M mutation is used to classify and define the molecular subgroup of DIPG, aiding in the understanding of its genetic drivers.

Gene→Variant (gene-first): 3021:K27M

Genes: 3021

Variants: K27M

[Paragraph-level] PMCID: PMC6368247 Section: RESULTS PassageIndex: 17

Evidence Type(s): Predictive, Oncogenic, Prognostic

Summary: Evidence Type: Predictive | Mutation: Y537S | Summary: The Y537S mutation is associated with resistance to fulvestrant treatment, indicating its predictive value in therapy response. Evidence Type: Oncogenic | Mutation: Y537S | Summary: The Y537S mutation contributes to tumor development or progression, as it is positively selected during treatment. Evidence Type: Prognostic | Mutation: Y537S | Summary: The presence of the Y537S mutation correlates with progression-free survival outcomes, suggesting its prognostic significance.

Gene→Variant (gene-first): 5728:Y537S

Genes: 5728

Variants: Y537S

[Paragraph-level] PMCID: PMC6368247 Section: RESULTS PassageIndex: 15

Evidence Type(s): Predictive

Summary: Evidence Type: Predictive | Mutation: Y537S | Summary: The variant Y537S is associated with treatment selection, indicating a correlation with response or resistance to specific therapies.

Gene→Variant (gene-first): 5728:Y537S

Genes: 5728

Variants: Y537S

[Paragraph-level] PMCID: PMC6368247 Section: RESULTS PassageIndex: 14

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: E542K | Summary: The E542K mutation shows limited evidence for positive selection, indicating its potential role in tumor development or progression. Evidence Type: Oncogenic | Mutation: E545K | Summary: The E545K mutation is one of the most common acquired variants, suggesting its contribution to tumor development or progression. Evidence Type: Oncogenic | Mutation: H1047L | Summary: The H1047L mutation is validated as an acquired variant, indicating its potential role in tumor development or progression. Evidence Type: Oncogenic | Mutation: H1047R | Summary: The H1047R mutation is validated as an acquired variant, indicating its potential role in tumor development or progression.

Gene→Variant (gene-first): 5290:E542K 5290:E545K 5290:H1047L 5290:H1047R

Genes: 5290

Variants: E542K E545K H1047L H1047R

[Paragraph-level] PMCID: PMC6368247 Section: RESULTS PassageIndex: 11

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: Q257X | Summary: The Q257X mutation in the RB1 gene is associated with the development of resistance to palbociclib and fulvestrant treatment, indicating its role in tumor progression. Evidence Type: Functional | Mutation: Q257X | Summary: The Q257X mutation is likely to result in abrogated Rb function due to the introduction of a stop codon, affecting the molecular function of the RB1 protein.

Gene→Variant (gene-first): 5925:Q257X

Genes: 5925

Variants: Q257X

[Paragraph-level] PMCID: PMC6368247 Section: RESULTS PassageIndex: 6

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: p.K569E | Summary: The p.K569E mutation in FGFR2 is described as an activating mutation that contributes to tumor development, particularly in the context of resistance to treatment with palbociclib plus fulvestrant. Evidence Type: Functional | Mutation: Q75E | Summary: The Q75E mutation in ESR1 is mentioned in relation to changes in dominant mutations and sub-clonal selection, suggesting it may have functional implications, although it is not recognized as a cause of resistance. Evidence Type: Oncogenic | Mutation: D538G | Summary: The D538G mutation in ESR1 was negatively selected during treatment, indicating its role in tumor progression and response to therapy, thus supporting its oncogenic potential.

Gene→Variant (gene-first): 2263:D538G 2099:Q75E 2263:p.K569E

Genes: 2263 2099

Variants: D538G Q75E p.K569E

[Paragraph-level] PMCID: PMC6368247 Section: RESULTS PassageIndex: 5

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: p.Q257X | Summary: The p.Q257X mutation in RB1 is associated with resistance to treatment, indicating its role in tumor development or progression. Evidence Type: Oncogenic | Mutation: p.N519fs | Summary: The p.N519fs mutation in RB1 is linked to the emergence of a resistant subclone, suggesting its contribution to tumor development or progression.

Gene→Variant (gene-first): 5925:p.N519fs 5925:p.Q257X

Genes: 5925

Variants: p.N519fs p.Q257X

[Paragraph-level] PMCID: PMC8203843 Section: RESULTS PassageIndex: 11

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: R132H | Summary: The IDH1 R132H mutation is associated with sensitivity to PARP inhibitors, indicating a correlation with treatment response. Evidence Type: Oncogenic | Mutation: R132H | Summary: The IDH1 R132H mutation contributes to tumor development and progression, particularly in the context of glioma.

Gene→Variant (gene-first): 3417:R132H

Genes: 3417

Variants: R132H

[Paragraph-level] PMCID: PMC7086303 Section: RESULTS PassageIndex: 3

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: G598V | Summary: The G598V mutation in EGFR is associated with increased sensitivity to the EGFR inhibitor afatinib, indicating a correlation with treatment response. Evidence Type: Oncogenic | Mutation: G598V | Summary: The G598V mutation is described as an activating mutation in EGFR, contributing to tumor development and progression in BTSC cultures.

Gene→Variant (gene-first): 1956:G598V

Genes: 1956

Variants: G598V

[Paragraph-level] PMCID: PMC5021039 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Predictive

Summary: Evidence Type: Predictive | Mutation: E709K | Summary: E709K is associated with moderate sensitivity to gefitinib or erlotinib, indicating its predictive value for response to these therapies. Evidence Type: Predictive | Mutation: G719X | Summary: G719X shows moderate sensitivities to gefitinib or erlotinib, suggesting it may predict response to these targeted therapies. Evidence Type: Predictive | Mutation: L858R | Summary: L858R is a common mutation that has been established to correlate with response to EGFR-tyrosine kinase inhibitors, indicating its predictive value. Evidence Type: Predictive | Mutation: L861Q | Summary: L861Q demonstrates moderate sensitivities to gefitinib or erlotinib, indicating its predictive value for response to these therapies. Evidence Type: Predictive | Mutation: S768I | Summary: S768I is associated with moderate sensitivities to gefitinib or erlotinib, suggesting it may predict response to these targeted therapies.

Gene→Variant (gene-first): 1956:E709K 1956:G719X 1956:L858R 1956:L861Q 1956:S768I

Genes: 1956

Variants: E709K G719X L858R L861Q S768I

[Paragraph-level] PMCID: PMC4378307 Section: RESULTS PassageIndex: 7

Evidence Type(s): Prognostic

Summary: Evidence Type: Prognostic | Mutation: G12D | Summary: The G12D subtype of KRAS mutation is associated with poor prognosis in progression-free survival (PFS). Evidence Type: Prognostic | Mutation: G12S | Summary: The G12S subtype of KRAS mutation is associated with poor prognosis in overall survival (OS).

Gene→Variant (gene-first): 3845:G12D 3845:G12S

Genes: 3845

Variants: G12D G12S

[Paragraph-level] PMCID: PMC1240052 Section: RESULTS PassageIndex: 19

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: L858R | Summary: The L858R mutation is associated with a response to the irreversible EGFR inhibitor CL-387,785, which shows greater effectiveness compared to gefitinib or erlotinib in inhibiting colony formation and autophosphorylation. Evidence Type: Oncogenic | Mutation: L858R | Summary: The L858R mutation contributes to tumor development or progression, as indicated by its role in transformation and autophosphorylation in cancer cells.

Gene→Variant (gene-first): 1956:L858R

Genes: 1956

Variants: L858R

[Paragraph-level] PMCID: PMC1240052 Section: RESULTS PassageIndex: 16

Evidence Type(s): Predictive

Summary: Evidence Type: Predictive | Mutation: G719S | Summary: The G719S mutation is associated with resistance to gefitinib, indicating its predictive value for therapy response in lung adenocarcinoma patients. Evidence Type: Predictive | Mutation: L747_E749del A750P | Summary: The L747_E749del A750P mutation correlates with sensitivity to gefitinib and erlotinib, supporting its predictive role in therapy response for lung adenocarcinoma. Evidence Type: Predictive | Mutation: L858R | Summary: The L858R mutation is linked to increased sensitivity to gefitinib and erlotinib, demonstrating its predictive significance for treatment outcomes in lung adenocarcinoma patients.

Gene→Variant (gene-first): 1956:G719S 1956:L747_E749del A750P 1956:L858R

Genes: 1956

Variants: G719S L747_E749del A750P L858R

[Paragraph-level] PMCID: PMC1240052 Section: RESULTS PassageIndex: 14

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: mutant EGFR | Summary: The mutant EGFR leads to constitutive activation of signaling pathways, indicating an alteration in molecular function related to cell survival. Evidence Type: Oncogenic | Mutation: mutant EGFR | Summary: The mutant EGFR contributes to tumor development by activating downstream signaling pathways, which are involved in promoting cell survival.

Gene→Variant (gene-first): 207:serine/threonine

Genes: 207

Variants: serine/threonine

[Paragraph-level] PMCID: PMC1240052 Section: RESULTS PassageIndex: 13

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: L858R | Summary: The L858R mutant EGFR alters molecular function by constitutively activating STAT signaling pathways and increasing STAT3-dependent gene expression in transformed cells. Evidence Type: Oncogenic | Mutation: L858R | Summary: The L858R mutation in EGFR contributes to tumor development as evidenced by its transformation of NIH-3T3 cells and activation of oncogenic signaling pathways.

Gene→Variant (gene-first): 1956:L858R

Genes: 1956

Variants: L858R

[Paragraph-level] PMCID: PMC1240052 Section: RESULTS PassageIndex: 12

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: L858R | Summary: The L858R mutation in EGFR leads to constitutive phosphorylation of Shc, indicating an alteration in molecular function related to downstream signaling pathways. Evidence Type: Oncogenic | Mutation: L858R | Summary: The L858R mutation in EGFR contributes to tumor development by causing constitutive activation and signaling alterations in cancer cells.

Gene→Variant (gene-first): 1956:L858R

Genes: 1956

Variants: L858R

[Paragraph-level] PMCID: PMC1240052 Section: RESULTS PassageIndex: 10

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: L858R | Summary: The L858R mutation in EGFR is associated with ligand-independent autophosphorylation, indicating that it alters molecular function related to receptor activation. Evidence Type: Oncogenic | Mutation: L858R | Summary: The L858R mutation contributes to tumor development and progression, as it is implicated in the activation of EGFR in lung adenocarcinoma.

Gene→Variant (gene-first): 1956:L858R

Genes: 1956

Variants: L858R

[Paragraph-level] PMCID: PMC1240052 Section: RESULTS PassageIndex: 6

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: L858R | Summary: The L858R mutant form of EGFR was shown to enhance anchorage-independent growth in hTBE cells, indicating its role in tumor development. Evidence Type: Oncogenic | Mutation: G719S | Summary: The G719S mutant form of EGFR conferred enhanced anchorage-independent growth in hTBE cells, supporting its contribution to tumor progression. Evidence Type: Oncogenic | Mutation: L747_E749del A750P | Summary: The L747_E749del A750P deletion and insertion mutants formed colonies in soft agar with high efficiency, suggesting their oncogenic potential. Evidence Type: Oncogenic | Mutation: D770_N771insNPG | Summary: The D770_N771insNPG insertion mutant also demonstrated the ability to form colonies in soft agar, indicating its role in tumor development. Evidence Type: Oncogenic | Mutation: V12 | Summary: The expression of H-RAS V12 in hTBE cells was mentioned in the context of anchorage-independent growth, suggesting its oncogenic behavior, although it is not an EGFR mutation.

Gene→Variant (gene-first): 1956:D770_N771insNPG 1956:G719S 1956:L747_E749del A750P 1956:L858R 3265:V12

Genes: 1956 3265

Variants: D770_N771insNPG G719S L747_E749del A750P L858R V12

[Paragraph-level] PMCID: PMC1240052 Section: RESULTS PassageIndex: 5

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: A750P | Summary: The A750P mutation was assessed for transforming activity and was shown to contribute to tumor development by promoting colony formation in soft agar. Evidence Type: Oncogenic | Mutation: D770_N771insNPG | Summary: The D770_N771insNPG mutation demonstrated transforming activity, contributing to tumor development as indicated by increased colony formation efficiency in NIH-3T3 cells. Evidence Type: Oncogenic | Mutation: L747_E749del | Summary: The L747_E749del mutation was shown to have transforming activity, contributing to tumor development through enhanced colony formation in soft agar. Evidence Type: Oncogenic | Mutation: L858R | Summary: The L858R mutation exhibited transforming activity, as evidenced by its comparable colony formation efficiency to the deletion mutant in NIH-3T3 cells. Evidence Type: Oncogenic | Mutation: G719S | Summary: The G719S mutation was part of the study assessing transforming activity, indicating its role in tumor development through altered cellular behavior in focus formation assays.

Gene→Variant (gene-first): 1956:A750P 1956:D770_N771insNPG 1956:E749del 1956:G719S 1956:L858R

Genes: 1956

Variants: A750P D770_N771insNPG E749del G719S L858R

[Paragraph-level] PMCID: PMC1240052 Section: RESULTS PassageIndex: 4

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: L858R | Summary: The L858R EGFR mutation contributes to tumor development as demonstrated by the formation of tumors in immunocompromised mice after injection of transformed NIH-3T3 fibroblasts. Evidence Type: Oncogenic | Mutation: G719S | Summary: The G719S EGFR mutation contributes to tumor development as shown by the formation of tumors in immunocompromised mice following the injection of transformed NIH-3T3 fibroblasts. Evidence Type: Functional | Mutation: D837A | Summary: The D837A mutation is described as kinase-inactive, indicating an alteration in molecular function compared to the wild-type EGFR.

Gene→Variant (gene-first): 1956:D837A 1956:G719S 1956:L858R

Genes: 1956

Variants: D837A G719S L858R

[Paragraph-level] PMCID: PMC1240052 Section: RESULTS PassageIndex: 3

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: G719S | Summary: The G719S mutation was shown to transform NIH-3T3 cells to anchorage independence, indicating its role in tumor development. Evidence Type: Oncogenic | Mutation: L858R | Summary: The L858R mutation was able to transform NIH-3T3 cells to anchorage independence, demonstrating its contribution to tumor progression. Evidence Type: Functional | Mutation: D837A | Summary: The D837A mutation is described as kinase-dead and failed to induce colony formation, indicating an alteration in molecular function.

Gene→Variant (gene-first): 1956:D837A 1956:G719S 1956:L858R

Genes: 1956

Variants: D837A G719S L858R

[Paragraph-level] PMCID: PMC2970593 Section: ABSTRACT PassageIndex: 6

Evidence Type(s): Functional, Predictive, Prognostic

Summary: Evidence Type: Functional | Mutation: L858R | Summary: The L858R mutation is described as a functional mutation that is activating in nature. Evidence Type: Predictive | Mutation: L858R | Summary: The L858R mutation is responsive to erlotinib, indicating a correlation with treatment response. Evidence Type: Prognostic | Mutation: L858R | Summary: Patients with the L858R mutation had a median follow-up time of 22 months, with some developing progressive disease and death, suggesting a correlation with disease outcome.

Gene→Variant (gene-first): 1956:L858R

Genes: 1956

Variants: L858R

[Paragraph-level] PMCID: PMC4159563 Section: RESULTS PassageIndex: 9

Evidence Type(s): Prognostic, Diagnostic, Oncogenic

Summary: Evidence Type: Prognostic | Mutation: K27M | Summary: The K27M mutation in histone H3 is associated with worse overall survival in DIPG patients compared to those without histone mutations, indicating its prognostic significance. Evidence Type: Diagnostic | Mutation: K27M | Summary: The presence of the K27M mutation in histone H3 is used to classify and define the subtype of tumors in DIPG patients, serving as a diagnostic marker. Evidence Type: Oncogenic | Mutation: K27M | Summary: The K27M mutation in histone H3 contributes to tumor development and progression in DIPG, indicating its oncogenic potential.

Gene→Variant (gene-first): 90:K27M

Genes: 90

Variants: K27M

[Paragraph-level] PMCID: PMC4159563 Section: RESULTS PassageIndex: 8

Evidence Type(s): Diagnostic, Oncogenic

Summary: Evidence Type: Diagnostic | Mutation: K27M | Summary: The K27M mutation is associated with specific histological features, which can be used to classify or define certain types of tumors. Evidence Type: Oncogenic | Mutation: K27M | Summary: The K27M mutation contributes to tumor development and progression, indicating its role as an oncogenic variant.

Gene→Variant (gene-first): 90:K27M

Genes: 90

Variants: K27M

[Paragraph-level] PMCID: PMC4159563 Section: RESULTS PassageIndex: 7

Evidence Type(s): Prognostic, Oncogenic, Functional

Summary: Evidence Type: Prognostic | Mutation: K27M | Summary: The K27M mutation is associated with worse overall survival in patients with leptomeningeal spread, averaging 0.63 years compared to 1.84 years for wild-type cases. Evidence Type: Oncogenic | Mutation: K27M | Summary: The K27M mutation contributes to tumor development, as indicated by its presence in cases of GBM and its association with leptomeningeal dissemination. Evidence Type: Functional | Mutation: p.Glu545Gly | Summary: The p.Glu545Gly alteration in PIK3CA is a mutation that may alter the molecular function of the protein, contributing to tumorigenesis. Evidence Type: Functional | Mutation: p.Gly328Val | Summary: The p.Gly328Val substitution in ACVR1 is a mutation that may affect the molecular function of the protein, potentially playing a role in tumor development.

Gene→Variant (gene-first): 90:K27M 5290:p.Glu545Gly 90:p.Gly328Val

Genes: 90 5290

Variants: K27M p.Glu545Gly p.Gly328Val

[Paragraph-level] PMCID: PMC7467277 Section: RESULTS PassageIndex: 5

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: chr8:208343-27992852 | Summary: The deletion observed on chromosome 8p, specifically spanning the region chr8:208343-27992852, is classified as a somatic copy number alteration (CNA) that contributes to tumor development or progression.

Gene→Variant (gene-first): NA:chr8:208343-27992852

Genes: NA

Variants: chr8:208343-27992852

[Paragraph-level] PMCID: PMC6843359 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: G309A | Summary: The G309A mutation is associated with receptor activation in the HER2 extracellular domain, indicating its role in tumor development. Evidence Type: Oncogenic | Mutation: G309E | Summary: The G309E mutation contributes to receptor activation in the HER2 extracellular domain, suggesting its involvement in tumor progression. Evidence Type: Oncogenic | Mutation: S310 | Summary: The S310 mutation is implicated in receptor activation within the HER2 extracellular domain, indicating its potential role in oncogenesis. Evidence Type: Oncogenic | Mutation: S310F | Summary: The S310F mutation induces receptor activation and is involved in the formation of active heterodimers with EGFR, contributing to tumor development. Evidence Type: Oncogenic | Mutation: S310Y | Summary: The S310Y mutation is associated with receptor activation in the HER2 extracellular domain, indicating its role in tumor progression.

Gene→Variant (gene-first): 2064:G309A 2064:G309E 2064:S310 2064:S310F 2064:S310Y

Genes: 2064

Variants: G309A G309E S310 S310F S310Y

[Paragraph-level] PMCID: PMC5652823 Section: RESULTS PassageIndex: 25

Evidence Type(s): Predictive, Prognostic

Summary: Evidence Type: Predictive | Mutation: T790M | Summary: The T790M mutation is associated with treatment response to osimertinib, as evidenced by the observed partial remissions and stable disease in patients treated with this therapy. Evidence Type: Prognostic | Mutation: T790M | Summary: The T790M mutation may correlate with disease outcome, as indicated by the progression-free survival (PFS) and overall survival (OS) data, although specific median values have not been reached.

Gene→Variant (gene-first): 1956:T790M

Genes: 1956

Variants: T790M

[Paragraph-level] PMCID: PMC5652823 Section: RESULTS PassageIndex: 24

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: T790M | Summary: The T790M mutation is associated with acquired resistance to 1st/2nd generation EGFR-TKI therapy and correlates with response to the third generation EGFR-TKI osimertinib. Evidence Type: Oncogenic | Mutation: T790M | Summary: The T790M mutation contributes to tumor development and progression, particularly in the context of resistance to EGFR-TKI therapy. Evidence Type: Oncogenic | Mutation: c.2155G>T; p.G719C | Summary: The c.2155G>T; p.G719C mutation is an activating mutation in the EGFR gene that contributes to tumor development. Evidence Type: Oncogenic | Mutation: V600E | Summary: The V600E mutation in the BRAF gene is associated with tumor development and progression, particularly in the context of the patient's cancer. Evidence Type: Oncogenic | Mutation: p.R248W | Summary: The p.R248W mutation in the TP53 gene is a common genetic variant in small-cell lung cancer that contributes to tumor development.

Gene→Variant (gene-first): 1956:G719C 1956:T790M 673:V600E 1956:c.2155G>T 1956:p.G719C 7157:p.R248W

Genes: 1956 673 7157

Variants: G719C T790M V600E c.2155G>T p.G719C p.R248W

[Paragraph-level] PMCID: PMC5652823 Section: RESULTS PassageIndex: 17

Evidence Type(s): Predictive

Summary: Evidence Type: Predictive | Mutation: E709A | Summary: The E709A mutation is associated with a sensitizing driver mutation that correlates with response to targeted therapy in patients. Evidence Type: Predictive | Mutation: G719S | Summary: The G719S mutation is associated with a sensitizing driver mutation that correlates with response to targeted therapy in patients.

Gene→Variant (gene-first): 1956:E709A 1956:G719S

Genes: 1956

Variants: E709A G719S