[Paragraph-level] PMCID: PMC7325368 Section: ABSTRACT PassageIndex: 2

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: B-RAFV600E | Summary: The B-RAFV600E mutation is associated with the response to the investigational therapy lifirafenib, indicating its predictive value for treatment sensitivity in patients with B-RAF-mutated solid tumors. Evidence Type: Oncogenic | Mutation: B-RAFV600E | Summary: The B-RAFV600E mutation contributes to tumor development or progression, as it is mentioned in the context of solid tumors with B-RAF mutations.

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

Genes: 673

Variants: B-RAFV600E

[Paragraph-level] PMCID: PMC7325368 Section: RESULTS PassageIndex: 11

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: G13D | Summary: The K-RAS G13D mutation is associated with treatment response, as patients with K-RAS mutations, including G13D, had confirmed responses and stable disease (SD) in the context of therapy. Evidence Type: Oncogenic | Mutation: G13D | Summary: The K-RAS G13D mutation contributes to tumor development or progression, as it is part of the K-RAS mutations observed in patients with endometrial cancer and NSCLC.

Gene→Variant (gene-first): 3845:G13D

Genes: 3845

Variants: G13D

[Paragraph-level] PMCID: PMC7325368 Section: RESULTS PassageIndex: 10

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: B-RAFV600E | Summary: The B-RAFV600E mutation is associated with responses to therapy, as evidenced by patients achieving partial responses (PR) and stable disease (SD) in clinical studies. Evidence Type: Oncogenic | Mutation: B-RAFV600E | Summary: The B-RAFV600E mutation contributes to tumor development and progression, as indicated by its presence in various cancer types and the observed treatment responses in patients.

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

Genes: 673

Variants: B-RAFV600E

[Paragraph-level] PMCID: PMC8033310 Section: ABSTRACT PassageIndex: 4

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: E545K | Summary: The E545K mutation in the PIK3CA gene is associated with tumor development or progression in TNBC cell lines. Evidence Type: Oncogenic | Mutation: H1047R | Summary: The H1047R mutation in the PIK3CA gene is associated with tumor development or progression in TNBC cell lines.

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

Genes: 5290

Variants: E545K H1047R

[Paragraph-level] PMCID: PMC6549573 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: G12D | Summary: The KRAS G12D mutation is associated with response to bortezomib therapy in non-small-cell lung cancer (NSCLC), although it is noted that this mutation alone is not a robust predictor of response. Evidence Type: Oncogenic | Mutation: G12D | Summary: The KRAS G12D mutation contributes to tumor development and progression in non-small-cell lung cancer (NSCLC) models.

Gene→Variant (gene-first): 3845:G12D

Genes: 3845

Variants: G12D

[Paragraph-level] PMCID: PMC10015977 Section: ABSTRACT PassageIndex: 6

Evidence Type(s): Oncogenic, Prognostic

Summary: Evidence Type: Oncogenic | Mutation: K700E | Summary: The K700E mutation is associated with superior overall survival in patients with MDS, indicating its role in tumor development or progression. Evidence Type: Prognostic | Mutation: K700E | Summary: The presence of the K700E mutation correlates with improved overall survival outcomes in MDS patients compared to those without this mutation. Evidence Type: Oncogenic | Mutation: R625 | Summary: The R625 mutation is part of recurrent non-K700E mutations associated with MDS, suggesting its contribution to tumor development or progression. Evidence Type: Prognostic | Mutation: R625 | Summary: The presence of R625, as a recurrent mutation, may correlate with disease outcomes in MDS patients, independent of therapy.

Gene→Variant (gene-first): 23451:K666 23451:K700 23451:K700E 23451:R625

Genes: 23451

Variants: K666 K700 K700E R625

[Paragraph-level] PMCID: PMC11551396 Section: RESULTS PassageIndex: 17

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: T790 | Summary: The T790 mutation is associated with the binding of TAK-788, indicating its role in tumor development or progression through its interaction with therapeutic agents.

Gene→Variant (gene-first): 1956:T790

Genes: 1956

Variants: T790

[Paragraph-level] PMCID: PMC11551396 Section: RESULTS PassageIndex: 16

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: C797 | Summary: The C797 mutation forms a covalent bond with the inhibitor, indicating an alteration in molecular function related to drug binding. Evidence Type: Oncogenic | Mutation: T790M | Summary: The T790M mutation is associated with an inactive kinase conformation, contributing to tumor development or progression. Evidence Type: Oncogenic | Mutation: V948R | Summary: The V948R mutation prevents the formation of the activating asymmetric dimer interaction, indicating its role in tumor development or progression.

Gene→Variant (gene-first): 1956:C797 1956:T790M 1956:V948R

Genes: 1956

Variants: C797 T790M V948R

[Paragraph-level] PMCID: PMC11551396 Section: RESULTS PassageIndex: 15

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: T790 | Summary: The T790 mutation is mentioned in the context of its interaction with inhibitors, suggesting its role in tumor development or progression as it is a gatekeeper residue involved in resistance mechanisms.

Gene→Variant (gene-first): 1956:T790

Genes: 1956

Variants: T790

[Paragraph-level] PMCID: PMC11551396 Section: RESULTS PassageIndex: 9

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: L858R | Summary: The L858R mutation shows a drug-sensitizing effect, correlating with greater potency against L858R EGFR compared to WT EGFR, indicating its relevance in therapy response. Evidence Type: Oncogenic | Mutation: L858R | Summary: The L858R mutation contributes to tumor development or progression, as it is associated with enhanced sensitivity to inhibitors compared to wild-type EGFR.

Gene→Variant (gene-first): 1956:L858R

Genes: 1956

Variants: L858R

[Paragraph-level] PMCID: PMC11551396 Section: RESULTS PassageIndex: 5

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: L858R | Summary: The L858R mutation is associated with enhanced inhibitor sensitivity due to its decreased affinity for ATP, which correlates with treatment response to EGFR TKIs. Evidence Type: Oncogenic | Mutation: L858R | Summary: The L858R mutation contributes to tumor development or progression, as indicated by its enhanced catalytic rates and sensitivity compared to other variants.

Gene→Variant (gene-first): 1956:L858R

Genes: 1956

Variants: L858R

[Paragraph-level] PMCID: PMC6843359 Section: RESULTS PassageIndex: 10

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: S310F | Summary: The S310F HER2 mutant was analyzed for its ability to form a heterodimer with EGFR, indicating that it alters molecular interactions and functions in a cellular context. Evidence Type: Oncogenic | Mutation: S310F | Summary: The S310F HER2 mutation is implicated in altered reactivity to therapeutic antibodies, suggesting a role in tumor development or progression.

Gene→Variant (gene-first): 2064:S310F

Genes: 2064

Variants: S310F

[Paragraph-level] PMCID: PMC6843359 Section: RESULTS PassageIndex: 8

Evidence Type(s): Oncogenic, Predictive

Summary: Evidence Type: Oncogenic | Mutation: S310F | Summary: The S310F HER2 mutant contributes to tumor development as indicated by its phosphorylation in response to EGFR signaling in 5637 cells. Evidence Type: Predictive | Mutation: S310F | Summary: The S310F HER2 mutant's response to anti-HER2 agents, particularly the lack of effect from trastuzumab on cell proliferation, suggests its predictive role in therapy resistance.

Gene→Variant (gene-first): 2064:S310F

Genes: 2064

Variants: S310F

[Paragraph-level] PMCID: PMC6843359 Section: RESULTS PassageIndex: 7

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: S310F | Summary: The S310F mutation is associated with tumor development or progression as indicated by its activation in the context of the HER2 mutant in cell studies.

Gene→Variant (gene-first): 2064:S310F

Genes: 2064

Variants: S310F

[Paragraph-level] PMCID: PMC6843359 Section: RESULTS PassageIndex: 6

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: S310F | Summary: The S310F HER2 mutant was confirmed to be expressed in 5637 cells through immunoprecipitation experiments, indicating that the variant alters the molecular function of HER2. Evidence Type: Oncogenic | Mutation: S310F | Summary: The expression of the S310F HER2 mutant in 5637 cells suggests that this somatic variant may contribute to tumor development or progression.

Gene→Variant (gene-first): 2064:S310F

Genes: 2064

Variants: S310F

[Paragraph-level] PMCID: PMC6843359 Section: RESULTS PassageIndex: 4

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: S310F | Summary: The S310F mutation is mentioned in the context of a bladder cancer cell line, indicating that it alters the molecular or biochemical function of HER2. Evidence Type: Oncogenic | Mutation: S310F | Summary: The presence of the S310F mutation in a bladder cancer cell line suggests that it may contribute to tumor development or progression.

Gene→Variant (gene-first): 2064:S310F

Genes: 2064

Variants: S310F

[Paragraph-level] PMCID: PMC5762309 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: V559D | Summary: The KIT V559D mutation is identified as a primary gain-of-function mutation in Gastrointestinal Stromal Tumors (GISTs), contributing to tumor development. Evidence Type: Functional | Mutation: V559D | Summary: The V559D mutation alters molecular function, as evidenced by its selectivity and efficacy in biochemical assays and signaling pathways. Evidence Type: Oncogenic | Mutation: L576P | Summary: The L576P mutation is mentioned as a primary mutant in the context of selective inhibition, indicating its role in tumor progression. Evidence Type: Oncogenic | Mutation: T670I | Summary: The T670I mutation is classified as a secondary mutant, contributing to tumor development in the context of selective inhibition. Evidence Type: Oncogenic | Mutation: V654A | Summary: The V654A mutation is noted as a secondary mutant involved in tumor progression, as indicated by its context in selective inhibition. Evidence Type: Oncogenic | Mutation: N822K | Summary: The N822K mutation is mentioned in the context of activation loop mutations, suggesting its contribution to tumor development. Evidence Type: Oncogenic | Mutation: D816V | Summary: The D816V mutation is described as an activation loop mutation, indicating its role in tumor progression.

Gene→Variant (gene-first): 3815:D816V 3815:L576P 3815:N822K 3815:T670I 3815:V559D 3815:V654A

Genes: 3815

Variants: D816V L576P N822K T670I V559D V654A

[Paragraph-level] PMCID: PMC5762309 Section: RESULTS PassageIndex: 11

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: V559D | Summary: The V559D mutation is associated with a response to the CHMFL-KIT-031 treatment, which shows a dose-dependent inhibition of tumor growth, indicating its predictive value for therapy response. Evidence Type: Oncogenic | Mutation: V559D | Summary: The V559D mutation contributes to tumor development or progression, as evidenced by its presence in a mouse model where tumor growth is being studied.

Gene→Variant (gene-first): 3815:V559D

Genes: 3815

Variants: V559D

[Paragraph-level] PMCID: PMC5762309 Section: RESULTS PassageIndex: 10

Evidence Type(s): Oncogenic, Predictive

Summary: Evidence Type: Oncogenic | Mutation: V559D | Summary: The V559D mutation is associated with tumor growth, indicating its role in tumor development or progression. Evidence Type: Predictive | Mutation: V559D | Summary: The passage suggests that CHMFL-KIT-031 inhibits tumor growth in a model with the V559D mutation, indicating a potential correlation with treatment response.

Gene→Variant (gene-first): 3815:V559D

Genes: 3815

Variants: V559D

[Paragraph-level] PMCID: PMC5762309 Section: RESULTS PassageIndex: 8

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: V559D | Summary: The KIT V559D mutant is selectively inhibited by CHMFL-KIT-031, indicating a correlation with response to this specific therapy. Evidence Type: Oncogenic | Mutation: V559D | Summary: The presence of the KIT V559D mutation suggests a role in tumor development or progression, as it is a specific mutant form of the KIT gene.

Gene→Variant (gene-first): 3815:V559D

Genes: 3815

Variants: V559D

[Paragraph-level] PMCID: PMC5762309 Section: RESULTS PassageIndex: 7

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: V559D | Summary: The V559D mutation is associated with strong binding to the inhibitor CHMFL-KIT-031, suggesting its role in tumor development or progression. Evidence Type: Functional | Mutation: L576P | Summary: The L576P mutation is mentioned in the context of binding assays, indicating that it alters molecular or biochemical function. Evidence Type: Functional | Mutation: A829P | Summary: The A829P mutation is also discussed in relation to binding assays, suggesting it alters molecular or biochemical function.

Gene→Variant (gene-first): 3815:A829P 3815:L576P 3815:V559D

Genes: 3815

Variants: A829P L576P V559D

[Paragraph-level] PMCID: PMC5762309 Section: RESULTS PassageIndex: 5

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: V559D | Summary: The V559D mutation alters the phosphorylation of KIT at specific sites, indicating a change in molecular function related to the mutant's response to treatment. Evidence Type: Oncogenic | Mutation: V559D | Summary: The V559D mutation contributes to tumor development or progression as it is associated with the anti-proliferative effects observed in transformed BaF3 cells.

Gene→Variant (gene-first): 3815:V559D

Genes: 3815

Variants: V559D

[Paragraph-level] PMCID: PMC5762309 Section: RESULTS PassageIndex: 2

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: V559D | Summary: The V559D mutation alters the molecular function of the KIT protein, as indicated by the selective inhibition of cell proliferation in BaF3-TEL-KIT-V559D cells. Evidence Type: Oncogenic | Mutation: V559D | Summary: The V559D mutation contributes to tumor development or progression, as it is associated with the proliferation of BaF3-TEL-KIT-V559D cells.

Gene→Variant (gene-first): 3815:V559D

Genes: 3815

Variants: V559D

[Paragraph-level] PMCID: PMC5002925 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Predictive, Oncogenic, Functional

Summary: Evidence Type: Predictive | Mutation: p.L755S | Summary: The ERBB2 p.L755S mutation was used to guide treatment with trastuzumab, indicating a correlation with therapy response. Evidence Type: Oncogenic | Mutation: p.L755S | Summary: The presence of the ERBB2 p.L755S mutation suggests it may contribute to tumor development or progression in colorectal cancer. Evidence Type: Functional | Mutation: p.L755S | Summary: The mutation is described in the context of its biological significance, indicating an alteration in molecular function. Evidence Type: Oncogenic | Mutation: p.N581S | Summary: The BRAF p.N581S mutation is mentioned as a genetic driver event, suggesting its role in tumor development or progression. Evidence Type: Oncogenic | Mutation: p.Q1429fs | Summary: The APC p.Q1429fs mutation is identified as a genetic driver event, indicating its contribution to tumor development or progression.

Gene→Variant (gene-first): 2064:p.L755S 673:p.N581S 324:p.Q1429fs

Genes: 2064 673 324

Variants: p.L755S p.N581S p.Q1429fs

[Paragraph-level] PMCID: PMC5002925 Section: RESULTS PassageIndex: 6

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: p.L755S | Summary: The ERBB2 p.L755S mutation is a heterozygous somatic mutation that contributes to tumor development or progression, as indicated by its presence in tumor samples and its allele frequency. Evidence Type: Oncogenic | Mutation: p.Q1429fs | Summary: The APC p.Q1429fs mutation is a heterozygous somatic mutation that is associated with tumor development or progression, as it was detected in tumor samples. Evidence Type: Oncogenic | Mutation: p.N518S | Summary: The BRAF p.N518S mutation is a heterozygous somatic mutation that contributes to tumor development or progression, as evidenced by its detection in tumor samples. Evidence Type: Functional | Mutation: p.N581S | Summary: The BRAF p.N581S mutation was verified and its biological effect was predicted using algorithms, indicating that it alters molecular or biochemical function.

Gene→Variant (gene-first): 2064:p.L755S 673:p.N518S 673:p.N581S 324:p.Q1429fs

Genes: 2064 673 324

Variants: p.L755S p.N518S p.N581S p.Q1429fs

[Paragraph-level] PMCID: PMC5002925 Section: RESULTS PassageIndex: 3

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: c.4285delC (p.Gln1429fs/p.Q1429fs) | Summary: The APC c.4285delC mutation is identified as a somatic variant that contributes to tumor development or progression in the context of rectal adenocarcinoma. Evidence Type: Oncogenic | Mutation: c.1742A>G (p.Asn581Ser/p.N581S) | Summary: The BRAF c.1742A>G mutation is a somatic variant that is implicated in tumor development or progression in the patient's rectal adenocarcinoma. Evidence Type: Oncogenic | Mutation: c.2264T>C (p.Leu755Ser/p.L755S) | Summary: The ERBB2 c.2264T>C mutation is a somatic variant that likely contributes to tumor development or progression, as indicated by its classification as an activating mutation.

Gene→Variant (gene-first): 673:c.1742A>G 2064:c.2264T>C 324:c.4285delC 673:p.Asn581Ser 324:p.Gln1429fs 2064:p.L755S 2064:p.Leu755Ser 673:p.N581S 324:p.Q1429fs

Genes: 673 2064 324

Variants: c.1742A>G c.2264T>C c.4285delC p.Asn581Ser p.Gln1429fs p.L755S p.Leu755Ser p.N581S p.Q1429fs

[Paragraph-level] PMCID: PMC10011885 Section: RESULTS PassageIndex: 24

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: Q61H | Summary: The KRAS Q61H mutation is associated with the emergence of subclonal mutations contributing to tumor development and progression, as indicated by its detection prior to disease progression. Evidence Type: Oncogenic | Mutation: Q61L | Summary: The KRAS Q61L mutation is part of the multiple subclonal KRAS mutations identified, which are implicated in tumor development and progression. Evidence Type: Oncogenic | Mutation: G12N | Summary: The KRAS G12N mutation is included among the subclonal mutations that contribute to tumor development and progression. Evidence Type: Oncogenic | Mutation: G13D | Summary: The KRAS G13D mutation is identified as a subclonal mutation that plays a role in tumor development and progression. Evidence Type: Oncogenic | Mutation: G12D | Summary: The NRAS G12D mutation is part of the identified mutations that contribute to tumor development and progression. Evidence Type: Functional | Mutation: A163G | Summary: The KDR A163G mutation is mentioned in the context of targeted sequencing, suggesting it may alter molecular or biochemical function. Evidence Type: Functional | Mutation: R106H | Summary: The MSH6 R106H mutation is identified in the context of targeted sequencing, indicating a potential alteration in molecular or biochemical function.

Gene→Variant (gene-first): 3791:A163G 3845:G12D 3845:G12N 3845:G13D 3845:Q61H 4893:Q61L 79811:R106H 673:V600E

Genes: 3791 3845 4893 79811 673

Variants: A163G G12D G12N G13D Q61H Q61L R106H V600E

[Paragraph-level] PMCID: PMC10011885 Section: RESULTS PassageIndex: 23

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: V600E | Summary: The BRAF V600E mutation was retained in patients at disease progression, indicating its role in tumor development or progression.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paragraph-level] PMCID: PMC10011885 Section: RESULTS PassageIndex: 19

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: V600E | Summary: The BRAF V600E mutation is associated with early changes in ctDNA levels that predict outcomes to combination vemurafenib and erlotinib therapy, indicating its role in treatment response. Evidence Type: Oncogenic | Mutation: V600E | Summary: The BRAF V600E mutation contributes to tumor development or progression, as indicated by its presence in ctDNA dynamics analyzed in the context of therapy.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paragraph-level] PMCID: PMC10011885 Section: RESULTS PassageIndex: 16

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: G13C | Summary: The NRAS G13C mutation was detected in a patient, indicating its potential role in tumor development or progression.

Gene→Variant (gene-first): 4893:G13C

Genes: 4893

Variants: G13C

[Paragraph-level] PMCID: PMC10011885 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 various cancers, including non-colorectal cancers. Evidence Type: Diagnostic | Mutation: V600E | Summary: The presence of the BRAF V600E mutation is used to classify patients with selected cancers, confirming their mutation-positive status.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paragraph-level] PMCID: PMC3287118 Section: RESULTS PassageIndex: 7

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: L858R | Summary: The L858R mutation is associated with tumor development or progression as it is mentioned in the context of samples with other mutations indicative of cancer. Evidence Type: Oncogenic | Mutation: T790M | Summary: The T790M mutation is associated with tumor development or progression as it is mentioned in the context of samples with other mutations indicative of cancer. Evidence Type: Oncogenic | Mutation: L861Q | Summary: The L861Q mutation is associated with tumor development or progression as it is mentioned in the context of samples with other mutations indicative of cancer. Evidence Type: Oncogenic | Mutation: S768I | Summary: The S768I mutation is associated with tumor development or progression as it is mentioned in the context of samples with other mutations indicative of cancer.

Gene→Variant (gene-first): 1956:L858R 1956:L861Q 1956:S768I 1956:T790M

Genes: 1956

Variants: L858R L861Q S768I T790M

[Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 13

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: G770 | Summary: The variant G770 is associated with sensitivity to EGFR TKIs such as dacomitinib, afatinib, and mobocertinib, indicating its predictive value for therapy response. Evidence Type: Oncogenic | Mutation: G770 | Summary: The G770 variant is implicated in tumor development or progression, as it is part of exon 20 insertion mutations in EGFR.

Gene→Variant (gene-first): 1956:G770

Genes: 1956

Variants: G770

[Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 12

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: G770 | Summary: The G770 mutation is associated with radiographic responses to the therapies poziotinib and mobocertinib in advanced lung cancers, indicating its predictive value for treatment response. Evidence Type: Oncogenic | Mutation: G770 | Summary: The G770 mutation is part of EGFR exon 20 insertion mutations that contribute to tumor development in advanced lung cancers, supporting its classification as oncogenic.

Gene→Variant (gene-first): 1956:G770

Genes: 1956

Variants: G770

[Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 10

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: G770 | Summary: The G770 mutation is associated with a lack of response to certain EGFR TKIs, indicating its predictive value regarding therapy resistance. Evidence Type: Oncogenic | Mutation: G770 | Summary: The G770 mutation is part of EGFR exon 20 insertion mutations that contribute to tumor development in patients with metastatic lung cancers.

Gene→Variant (gene-first): 1956:G770

Genes: 1956

Variants: G770

[Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 9

Evidence Type(s): Oncogenic, Diagnostic

Summary: Evidence Type: Oncogenic | Mutation: G770 | Summary: The passage discusses advanced lung cancers harboring EGFR Exon 20 insertion mutations, indicating that the G770 mutation contributes to tumor development or progression. Evidence Type: Diagnostic | Mutation: G770 | Summary: The mention of advanced lung cancers associated with EGFR Exon 20 insertion mutations suggests that the G770 mutation is used to classify or define a specific subtype of lung cancer.

Gene→Variant (gene-first): 1956:G770

Genes: 1956

Variants: G770

[Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 6

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: V769dupASV | Summary: The V769dupASV mutation is associated with a higher IC50 for afatinib and dacomitinib, indicating a correlation with resistance to these therapies. Evidence Type: Oncogenic | Mutation: V769dupASV | Summary: The V769dupASV mutation is implicated in driving proliferation in Ba/F3 cells, suggesting its role in tumor development or progression.

Gene→Variant (gene-first): 1956:V769dupASV

Genes: 1956

Variants: V769dupASV

[Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 3

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: G770 | Summary: The G770 mutation is part of the EGFR exon 20 insertion mutations, which are known to contribute to tumor development or progression. Evidence Type: Functional | Mutation: G770 | Summary: The G770 mutation alters molecular or biochemical function as it is associated with changes in the EGFR protein due to the insertion mutations.

Gene→Variant (gene-first): 1956:G770

Genes: 1956

Variants: G770

[Paragraph-level] PMCID: PMC9338780 Section: ABSTRACT PassageIndex: 8

Evidence Type(s): Predictive, Prognostic, Oncogenic

Summary: Evidence Type: Predictive | Mutation: V600E | Summary: The BRAF V600E mutation is associated with a substantial clinical benefit from the combination of dabrafenib and trametinib, indicating its predictive value for treatment response in patients with ATC. Evidence Type: Prognostic | Mutation: V600E | Summary: The presence of the BRAF V600E mutation correlates with improved long-term survival in patients treated with dabrafenib plus trametinib, suggesting its prognostic significance in this context. Evidence Type: Oncogenic | Mutation: V600E | Summary: The BRAF V600E mutation contributes to tumor development and progression in anaplastic thyroid carcinoma (ATC), indicating its oncogenic role in this aggressive cancer type.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

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

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: V600E | Summary: The BRAF V600E mutation is evaluated in the context of a study assessing the response to the combination of dabrafenib and trametinib, indicating its predictive value for treatment response. Evidence Type: Oncogenic | Mutation: V600E | Summary: The BRAF V600E mutation is implicated in the development of rare cancers, supporting its role as an oncogenic variant contributing to tumor progression.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

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

Evidence Type(s): Predictive, Diagnostic, Oncogenic

Summary: Evidence Type: Predictive | Mutation: V600E | Summary: The BRAF V600E mutation is associated with response to combined therapy with dabrafenib and trametinib in anaplastic thyroid cancer, indicating its predictive value for treatment efficacy. Evidence Type: Diagnostic | Mutation: V600E | Summary: The presence of the BRAF V600E mutation is used to define and classify anaplastic thyroid cancer, supporting its role as a diagnostic marker for this disease subtype. Evidence Type: Oncogenic | Mutation: V600E | Summary: The BRAF V600E mutation contributes to tumor development and progression in anaplastic thyroid cancer, indicating its oncogenic potential.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paragraph-level] PMCID: PMC8727519 Section: ABSTRACT PassageIndex: 6

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: T790M | Summary: The T790M mutation is associated with resistance to first-generation EGFR tyrosine kinase inhibitors, suggesting its role in predicting treatment response in NSCLC patients. Evidence Type: Oncogenic | Mutation: T790M | Summary: The T790M mutation contributes to tumor development and progression in the context of EGFR-mutated non-small cell lung cancer (NSCLC).

Gene→Variant (gene-first): 1956:T790M

Genes: 1956

Variants: T790M

[Paragraph-level] PMCID: PMC8727519 Section: ABSTRACT PassageIndex: 4

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: L858R | Summary: The L858R mutation in EGFR is associated with lung adenocarcinoma and contributes to tumor development. Evidence Type: Oncogenic | Mutation: T790M | Summary: The T790M mutation is identified as a potential resistance mechanism to icotinib treatment, indicating its role in tumor progression.

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

Genes: 1956

Variants: L858R T790M

[Paragraph-level] PMCID: PMC11272140 Section: ABSTRACT PassageIndex: 8

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: G2032R | Summary: The G2032R mutation is associated with acquired resistance to therapy, indicating its relevance in predicting treatment response and sensitivity to taletrectinib. Evidence Type: Oncogenic | Mutation: G2032R | Summary: The G2032R mutation is mentioned in the context of acquired resistance mutations, suggesting its role in tumor development or progression.

Gene→Variant (gene-first): 6098:G2032R

Genes: 6098

Variants: G2032R

[Paragraph-level] PMCID: PMC11272140 Section: ABSTRACT PassageIndex: 6

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: G2032R | Summary: The G2032R mutation is associated with a response rate of 67% in patients, indicating its potential predictive value for treatment outcomes. Evidence Type: Oncogenic | Mutation: G2032R | Summary: The presence of the G2032R mutation suggests a role in tumor development or progression, as it is linked to patient responses in a cancer treatment context.

Gene→Variant (gene-first): 6098:G2032R

Genes: 6098

Variants: G2032R

[Paragraph-level] PMCID: PMC11272140 Section: ABSTRACT PassageIndex: 2

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: G2032R | Summary: The G2032R mutation is associated with a favorable response to taletrectinib, a ROS1 tyrosine kinase inhibitor, indicating its predictive value for treatment response in ROS1+ non-small cell lung cancer. Evidence Type: Oncogenic | Mutation: G2032R | Summary: The G2032R mutation contributes to tumor development or progression in the context of ROS1+ non-small cell lung cancer, supporting its classification as an oncogenic variant.

Gene→Variant (gene-first): 6098:G2032R

Genes: 6098

Variants: G2032R

[Paragraph-level] PMCID: PMC5029699 Section: RESULTS PassageIndex: 31

Evidence Type(s): Predictive, Functional, Oncogenic

Summary: Evidence Type: Predictive | Mutation: K650E | Summary: The K650E mutation had moderate effects on the efficacy of all inhibitors, indicating a correlation with treatment response. Evidence Type: Predictive | Mutation: N540K | Summary: The N540K substitution affected the efficacy of AZD4547 more significantly, suggesting its role in treatment sensitivity. Evidence Type: Predictive | Mutation: N540S | Summary: The N540S mutation had a pronounced effect on the efficacy of JNJ42756493, indicating its impact on treatment response. Evidence Type: Predictive | Mutation: V555M | Summary: The V555M mutation conferred resistance to AZ12908010 and significantly impacted the efficacy of AZD4547, highlighting its role in treatment resistance. Evidence Type: Functional | Mutation: I538V | Summary: The I538V mutation had a substantial effect on drug binding, indicating an alteration in molecular function. Evidence Type: Oncogenic | Mutation: R669G | Summary: The highly activating R669G mutation contributes to tumor development or progression, supporting its oncogenic potential.

Gene→Variant (gene-first): 2263:I538 2263:I538V 2261:K650E 2261:N540 2261:N540K 2261:N540S 2261:R669G 2261:V555M

Genes: 2263 2261

Variants: I538 I538V K650E N540 N540K N540S R669G V555M

[Paragraph-level] PMCID: PMC5029699 Section: RESULTS PassageIndex: 29

Evidence Type(s): Oncogenic, Predictive

Summary: Evidence Type: Oncogenic | Mutation: V555M | Summary: The V555M mutation in FGFR3 is described as a gatekeeper mutation that reduces drug binding, indicating its role in tumor development or progression. Evidence Type: Predictive | Mutation: V555M | Summary: The passage suggests that the V555M mutation may affect drug efficacy, implying a correlation with response or resistance to specific therapies.

Gene→Variant (gene-first): 2261:V555M

Genes: 2261

Variants: V555M

[Paragraph-level] PMCID: PMC5029699 Section: RESULTS PassageIndex: 21

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: R669 | Summary: The R669 mutation in FGFR3 is associated with cancer, indicating its contribution to tumor development or progression. Evidence Type: Functional | Mutation: R to G | Summary: The R to G replacement in FGFR1 KD alters the molecular activity of the protein, suggesting a functional change. Evidence Type: Oncogenic | Mutation: R675G | Summary: The R675G variant in FGFR1 KD shows higher activity compared to wild type, indicating its potential role in tumor development or progression.

Gene→Variant (gene-first): 2260:R to G 2261:R669 2260:R675G

Genes: 2260 2261

Variants: R to G R669 R675G

[Paragraph-level] PMCID: PMC5029699 Section: RESULTS PassageIndex: 19

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: D617G | Summary: The D617G mutation is predicted to reduce protein production or completely inactivate the kinase, indicating a functional alteration. Evidence Type: Functional | Mutation: E466K | Summary: The E466K mutation is predicted to reduce protein production or completely inactivate the kinase, indicating a functional alteration. Evidence Type: Functional | Mutation: G637W | Summary: The G637W mutation is predicted to reduce protein production or completely inactivate the kinase, indicating a functional alteration. Evidence Type: Oncogenic | Mutation: R669 | Summary: The R669 mutation is located within an identified cluster of observed A-loop cancer mutations, suggesting its contribution to tumor development or progression.

Gene→Variant (gene-first): 2261:D617G 2263:E466K 2260:G637W 2261:R669

Genes: 2261 2263 2260

Variants: D617G E466K G637W R669

[Paragraph-level] PMCID: PMC5029699 Section: RESULTS PassageIndex: 17

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: G697C | Summary: The G697C mutation does not affect kinase activity directly as measured in vitro, suggesting it may alter FGFR3 function in a cellular setting. Evidence Type: Oncogenic | Mutation: K650E | Summary: The K650E mutation is associated with a transformed phenotype and anchorage independent growth in cell lines, indicating its role in tumor development. Evidence Type: Oncogenic | Mutation: N540K | Summary: The N540K mutation is also linked to a transformed phenotype and anchorage independent growth in cell lines, supporting its contribution to tumor progression.

Gene→Variant (gene-first): 2261:G697C 2261:K650E 2261:N540K

Genes: 2261

Variants: G697C K650E N540K

[Paragraph-level] PMCID: PMC5029699 Section: RESULTS PassageIndex: 16

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: K650E | Summary: The K650E mutation is associated with altered kinase activity, indicating that it affects the molecular function of the FGFR3 protein. Evidence Type: Oncogenic | Mutation: K650E | Summary: The K650E mutation is described as a highly activating variant, suggesting its contribution to tumor development or progression.

Gene→Variant (gene-first): 2261:K650E

Genes: 2261

Variants: K650E

[Paragraph-level] PMCID: PMC5029699 Section: RESULTS PassageIndex: 14

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: G697C | Summary: The G697C mutation is mentioned in the context of FGFR3 KD activity, indicating that it alters molecular or biochemical function. Evidence Type: Oncogenic | Mutation: G697C | Summary: The G697C mutation is described as one of the hotspots, suggesting its contribution to tumor development or progression.

Gene→Variant (gene-first): 2261:G697C

Genes: 2261

Variants: G697C

[Paragraph-level] PMCID: PMC5029699 Section: RESULTS PassageIndex: 7

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: K650 | Summary: The K650 mutation is located in a hot spot within the A-loop of the FGFR3 kinase domain, suggesting its contribution to tumor development or progression. Evidence Type: Oncogenic | Mutation: R669 | Summary: The R669 mutation is situated near the A-loop of the FGFR3 kinase domain, indicating its potential role in tumor development or progression. Evidence Type: Functional | Mutation: N540 | Summary: The N540 mutation is part of the molecular brake in the FGFR3 structure, suggesting it alters molecular or biochemical function. Evidence Type: Functional | Mutation: I538 | Summary: The I538 mutation is also part of the molecular brake in the FGFR3 structure, indicating it may affect molecular or biochemical function.

Gene→Variant (gene-first): 2263:I538 2261:K650 2261:N540 2261:R669

Genes: 2263 2261

Variants: I538 K650 N540 R669

[Paragraph-level] PMCID: PMC5029699 Section: RESULTS PassageIndex: 5

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: K650 | Summary: The K650 mutation in FGFR3 is associated with tumor development and progression, particularly in cancer contexts. Evidence Type: Oncogenic | Mutation: N540 | Summary: The N540 mutation in FGFR3 contributes to tumor development and is noted in the context of cancer. Evidence Type: Oncogenic | Mutation: N540K | Summary: The N540K mutation is frequently observed in cancer and is indicative of oncogenic behavior in FGFR3.

Gene→Variant (gene-first): 2261:K650 2261:N540 2261:N540K

Genes: 2261

Variants: K650 N540 N540K

[Paragraph-level] PMCID: PMC5029699 Section: RESULTS PassageIndex: 4

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: K650 | Summary: The mutation K650 in FGFR3 is identified as a frequently mutated hotspot in cancer, indicating its contribution to tumor development or progression. Evidence Type: Oncogenic | Mutation: G697 | Summary: The mutation G697 is noted as a frequently mutated hotspot in FGFR3, suggesting its role in tumor development or progression.

Gene→Variant (gene-first): 2261:G697 2261:G697C 2261:K650 2261:N540

Genes: 2261

Variants: G697 G697C K650 N540

[Paragraph-level] PMCID: PMC9402235 Section: RESULTS PassageIndex: 9

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: c.236A>G (p.Tyr79Cys) | Summary: The c.236A>G (p.Tyr79Cys) variant is described as a somatic variant in renal cell carcinomas (RCCs) and contributes to tumor development in VHL-independent renal tumorigenesis. Evidence Type: Oncogenic | Mutation: c.274G>A (p.Glu92Lys) | Summary: The c.274G>A (p.Glu92Lys) variant is identified as a somatic variant in RCC, contributing to tumor development. Evidence Type: Oncogenic | Mutation: c.74A>T (p.Asp25Val) | Summary: The c.74A>T (p.Asp25Val) variant is reported as a somatic variant in RCC, indicating its role in tumor development. Evidence Type: Oncogenic | Mutation: c.311T>A (p.Leu104Gln) | Summary: The c.311T>A (p.Leu104Gln) variant is noted as a somatic variant in RCC, suggesting its involvement in tumor progression. Evidence Type: Functional | Mutation: c.261_272del (p.Thr88_Pro91del) | Summary: The c.261_272del (p.Thr88_Pro91del) variant is described as an in-frame deletion that alters molecular function, contributing to the understanding of ELOC variants in RCC.

Gene→Variant (gene-first): 3091:c.236A>G 6921:c.261_272del 5979:c.274G>A 6921:c.311T>A 3855:c.74A>T 3855:p.Asp25Val 7409:p.Glu92Lys 6921:p.Leu104Gln 6921:p.Thr88_Pro91del 3091:p.Tyr79Cys

Genes: 3091 6921 5979 3855 7409

Variants: c.236A>G c.261_272del c.274G>A c.311T>A c.74A>T p.Asp25Val p.Glu92Lys p.Leu104Gln p.Thr88_Pro91del p.Tyr79Cys

[Paragraph-level] PMCID: PMC9402235 Section: RESULTS PassageIndex: 5

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: c.236A>G (p.Tyr79Cys) | Summary: The de novo missense variant c.236A>G (p.Tyr79Cys) alters the molecular function of the ELOC gene, as the Tyr79 residue is critical for forming a hydrogen bond with the Pro154 residue within the pVHL alpha domain. Evidence Type: Oncogenic | Mutation: c.236A>G (p.Tyr79Cys) | Summary: The missense variant c.236A>G (p.Tyr79Cys) is implicated in tumor development due to its location in the tetramerization domain of the ELOC gene, which is essential for its function in the context of VHL disease.

Gene→Variant (gene-first): 3091:Tyr79 3091:Y79 3091:c.236A>G 3091:p.Tyr79Cys

Genes: 3091

Variants: Tyr79 Y79 c.236A>G p.Tyr79Cys

[Paragraph-level] PMCID: PMC9402235 Section: ABSTRACT PassageIndex: 2

Evidence Type(s): Predisposing, Oncogenic, Functional

Summary: Evidence Type: Predisposing | Mutation: c.236A>G; p.Tyr79Cys | Summary: The variant is described as a de novo pathogenic variant identified in a proband with VHL disease, indicating it may confer inherited risk for the disease. Evidence Type: Oncogenic | Mutation: c.236A>G; p.Tyr79Cys | Summary: The p.Tyr79Cys substitution is noted as a mutational hotspot in sporadic VHL-competent renal cell carcinoma (RCC), suggesting it contributes to tumor development or progression. Evidence Type: Functional | Mutation: c.236A>G; p.Tyr79Cys | Summary: The variant has been shown to mimic the effects of pVHL deficiency on hypoxic signaling, indicating an alteration in molecular function.

Gene→Variant (gene-first): 3091:c.236A>G 3091:p.Tyr79Cys

Genes: 3091

Variants: c.236A>G p.Tyr79Cys

[Paragraph-level] PMCID: PMC6594036 Section: RESULTS PassageIndex: 8

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: 2690A > G | Summary: The mutation 2690A > G in the TEK gene is associated with tumor development or progression. Evidence Type: Oncogenic | Mutation: c.2752A > G | Summary: The mutation c.2752A > G in the TEK gene is associated with tumor development or progression. Evidence Type: Functional | Mutation: Arg918Cys | Summary: The mutation Arg918Cys is likely to alter molecular or biochemical function. Evidence Type: Functional | Mutation: Tyr897Cys | Summary: The mutation Tyr897Cys is likely to alter molecular or biochemical function.

Gene→Variant (gene-first): 7010:2690A > G 3845:Arg918Cys 7010:Tyr897Cys 7010:c.2752A > G

Genes: 7010 3845

Variants: 2690A > G Arg918Cys Tyr897Cys c.2752A > G

[Paragraph-level] PMCID: PMC7612117 Section: ABSTRACT PassageIndex: 1

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

Summary: Evidence Type: Oncogenic | Mutation: p.L1363P | Summary: The BRCA1 p.L1363P variant contributes to tumor development, as it leads to the acceleration of mammary tumors in genetically engineered mice, indicating its role in cancer progression. Evidence Type: Functional | Mutation: p.L1363P | Summary: The BRCA1 p.L1363P variant disrupts the interaction with PALB2 and results in HRR incompetence, demonstrating an alteration in molecular function. Evidence Type: Predictive | Mutation: p.L1363P | Summary: The BRCA1 p.L1363P variant is responsive to cisplatin and PARP inhibition, indicating its potential correlation with treatment response. Evidence Type: Prognostic | Mutation: p.L1363P | Summary: The presence of the BRCA1 p.L1363P variant is associated with distinct histopathological features and stable DNA copy number profiles in tumors, which may correlate with disease outcome.

Gene→Variant (gene-first): 7158:p.L1363P

Genes: 7158

Variants: p.L1363P

[Paragraph-level] PMCID: PMC7612117 Section: RESULTS PassageIndex: 15

Evidence Type(s): Predictive, Functional, Oncogenic

Summary: Evidence Type: Predictive | Mutation: L1363P | Summary: The L1363P mutation in BRCA1 is associated with a better response to cisplatin and the PARP inhibitor AZD2461 compared to other tumor types, indicating its predictive value for therapy response. Evidence Type: Functional | Mutation: L1363P | Summary: The L1363P mutation alters the molecular function of BRCA1, as evidenced by the compromised RAD51 foci formation in response to gamma-radiation, indicating a partial HRR defect. Evidence Type: Oncogenic | Mutation: L1363P | Summary: The BRCA1 L1363P variant is implicated in increasing the risk of developing breast cancer, suggesting its role in tumor development or progression.

Gene→Variant (gene-first): 7158:L1363P 7158:p.L1363P

Genes: 7158

Variants: L1363P p.L1363P

[Paragraph-level] PMCID: PMC7612117 Section: RESULTS PassageIndex: 14

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: L1363P | Summary: The L1363P mutation is associated with a response to cisplatin and PARP inhibition in mammary tumors, indicating its predictive value for therapy response. Evidence Type: Oncogenic | Mutation: L1363P | Summary: The L1363P mutation contributes to tumor development or progression in mammary tumors, supporting its classification as an oncogenic variant.

Gene→Variant (gene-first): 7158:L1363P

Genes: 7158

Variants: L1363P

[Paragraph-level] PMCID: PMC7612117 Section: RESULTS PassageIndex: 13

Evidence Type(s): Oncogenic, Diagnostic

Summary: Evidence Type: Oncogenic | Mutation: L1363P | Summary: The KB1(L1363P)P mutation is associated with the development of carcinosarcomas, indicating its contribution to tumor progression and classification as an oncogenic variant. Evidence Type: Diagnostic | Mutation: L1363P | Summary: The presence of the KB1(L1363P)P mutation helps define and classify the tumors as carcinosarcomas, distinguishing them from adenocarcinomas based on their histological characteristics.

Gene→Variant (gene-first): 7158:L1363P 7158:p.L1363P

Genes: 7158

Variants: L1363P p.L1363P

[Paragraph-level] PMCID: PMC7612117 Section: RESULTS PassageIndex: 12

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: L1363P | Summary: The L1363P mutation is associated with mammary tumors exhibiting EMT-like phenotypes, indicating its contribution to tumor development or progression. Evidence Type: Functional | Mutation: L1363P | Summary: The L1363P mutation alters molecular or biochemical function, as suggested by the EMT-like phenotypes observed in the tumors.

Gene→Variant (gene-first): 7158:L1363P

Genes: 7158

Variants: L1363P

[Paragraph-level] PMCID: PMC7612117 Section: RESULTS PassageIndex: 11

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: p.L1363P | Summary: The Brca1 p.L1363P variant is functionally important as it compromises BRCA1-mediated homologous recombination repair (HRR), indicating an alteration in molecular function. Evidence Type: Oncogenic | Mutation: p.L1363P | Summary: The Brca1 p.L1363P variant contributes to tumor development, as evidenced by the accelerated tumor formation in mouse models compared to controls, indicating its role in oncogenesis.

Gene→Variant (gene-first): 7158:L1363P 7158:p.L1363P

Genes: 7158

Variants: L1363P p.L1363P

[Paragraph-level] PMCID: PMC7612117 Section: RESULTS PassageIndex: 10

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: p.L1363P | Summary: The variant p.L1363P in Brca1 is associated with a defect in mammary tumor suppression, indicating its role in tumor development or progression.

Gene→Variant (gene-first): 7158:p.L1363P

Genes: 7158

Variants: p.L1363P

[Paragraph-level] PMCID: PMC7302243 Section: RESULTS PassageIndex: 3

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: T790M | Summary: The T790M mutation is associated with acquired resistance to EGFR-TKI therapy in PC9/GR cells, indicating its role in treatment response. Evidence Type: Oncogenic | Mutation: T790M | Summary: The T790M mutation contributes to tumor progression by conferring resistance to targeted therapies in the context of EGFR-driven cancer.

Gene→Variant (gene-first): 1956:T790M

Genes: 1956

Variants: T790M

[Paragraph-level] PMCID: PMC3378484 Section: RESULTS PassageIndex: 17

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: E545K | Summary: The E545K mutation is associated with enhanced lipid binding and increased basal activity, indicating its role in tumor development or progression.

Gene→Variant (gene-first): 5290:E545K

Genes: 5290

Variants: E545K

[Paragraph-level] PMCID: PMC3378484 Section: RESULTS PassageIndex: 16

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: C420R | Summary: The C420R mutation is characterized as activating, indicating its contribution to tumor development or progression. Evidence Type: Oncogenic | Mutation: E545K | Summary: The E545K mutation is described as activating, suggesting it plays a role in tumor development or progression. Evidence Type: Oncogenic | Mutation: G1049R | Summary: The G1049R mutation is noted to be activating, which implies its involvement in tumor development or progression. Evidence Type: Oncogenic | Mutation: H1047L | Summary: The H1047L mutation is characterized as activating, indicating its contribution to tumor development or progression. Evidence Type: Oncogenic | Mutation: H1047R | Summary: The H1047R mutation is described as activating, suggesting it plays a role in tumor development or progression. Evidence Type: Oncogenic | Mutation: M1043I | Summary: The M1043I mutation is noted to be activating, which implies its involvement in tumor development or progression.

Gene→Variant (gene-first): 5290:C420R 5290:E545K 5290:G1049R 5290:H1047L 5290:H1047R 5290:M1043I 5295:N564D

Genes: 5290 5295

Variants: C420R E545K G1049R H1047L H1047R M1043I N564D

[Paragraph-level] PMCID: PMC3378484 Section: RESULTS PassageIndex: 9

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: D915N | Summary: The D915N mutation in the catalytic DRH motif of p110alpha is associated with altered molecular function, specifically in the context of lipid binding and activation of the p110/p85 complex. Evidence Type: Oncogenic | Mutation: D915N | Summary: The D915N mutation is described as a cancer-linked mutation, indicating its contribution to tumor development or progression.

Gene→Variant (gene-first): 5290:D915N

Genes: 5290

Variants: D915N

[Paragraph-level] PMCID: PMC3378484 Section: RESULTS PassageIndex: 6

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: H1047R | Summary: The H1047R mutation in p110alpha is described as an oncogenic mutant, indicating its contribution to tumor development or progression. Evidence Type: Functional | Mutation: H1047R | Summary: The passage discusses structural features of the H1047R mutant, suggesting that this variant alters molecular or biochemical function, particularly in relation to its conformation and interactions within the protein structure.

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

Genes: 5290

Variants: H1047R

[Paragraph-level] PMCID: PMC3378484 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: E545K | Summary: The E545K mutant shows the highest basal activity and lipid binding, mimicking the activated wild-type p110alpha, indicating its role in tumor development. Evidence Type: Oncogenic | Mutation: H1047R | Summary: The H1047R mutant exhibits increased basal kinase activities and lipid binding, contributing to tumor progression. Evidence Type: Oncogenic | Mutation: C420R | Summary: The C420R mutation shows increased basal kinase activity and lipid binding, suggesting its involvement in oncogenesis. Evidence Type: Oncogenic | Mutation: M1043I | Summary: The M1043I mutation is associated with increased basal kinase activity and lipid binding, indicating its oncogenic potential. Evidence Type: Oncogenic | Mutation: H1047L | Summary: The H1047L mutation demonstrates increased basal kinase activity and lipid binding, contributing to tumor development. Evidence Type: Oncogenic | Mutation: G1049R | Summary: The G1049R mutation shows increased basal kinase activity and lipid binding, suggesting its role in oncogenesis. Evidence Type: Functional | Mutation: N564D | Summary: The N564D mutation is associated with altered lipid binding activities, indicating a change in molecular function.

Gene→Variant (gene-first): 5290:C420R 5290:E545K 5290:G1049R 5290:H1047L 5290:H1047R 5290:M1043I 5295:N564D

Genes: 5290 5295

Variants: C420R E545K G1049R H1047L H1047R M1043I N564D

[Paragraph-level] PMCID: PMC4239128 Section: RESULTS PassageIndex: 2

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: 1799T > A; p.V600E | Summary: The mutation p.V600E in BRAF is associated with a potential vulnerability to BRAF inhibition, indicating a correlation with response to therapy using dabrafenib and trametinib. Evidence Type: Oncogenic | Mutation: 1799T > A; p.V600E | Summary: The BRAF p.V600E mutation is implicated in tumor development and progression, contributing to the malignancy's characteristics.

Gene→Variant (gene-first): 673:1799T > A 673:p.V600E

Genes: 673

Variants: 1799T > A p.V600E

[Paragraph-level] PMCID: PMC4675689 Section: RESULTS PassageIndex: 8

Evidence Type(s): Predictive, Functional, Oncogenic

Summary: Evidence Type: Predictive | Mutation: D835 | Summary: The D835 mutation is associated with sensitivity to type II inhibitors, suggesting that certain D835 mutants may respond to therapy despite being excluded from clinical trials. Evidence Type: Functional | Mutation: D835 | Summary: The D835 residue is critical for stabilizing the inactive conformation of FLT3, and mutations at this site affect the molecular interactions necessary for type II inhibitor binding. Evidence Type: Oncogenic | Mutation: D835 | Summary: The D835 mutation contributes to tumor development by influencing the kinase's conformation and resistance to inhibitors. Evidence Type: Predictive | Mutation: D835N/E | Summary: The D835N/E mutations may retain sensitivity to type II FLT3 TKIs, indicating a potential response to therapy. Evidence Type: Functional | Mutation: D835N/E | Summary: The D835N/E mutations preserve critical structural features necessary for the binding of type II inhibitors, affecting the molecular function of FLT3. Evidence Type: Oncogenic | Mutation: D835N/E | Summary: The D835N/E mutations are implicated in tumor progression by maintaining a conformation that allows for continued kinase activity despite treatment.

Gene→Variant (gene-first): 2322:D835 2322:D835N/E

Genes: 2322

Variants: D835 D835N/E

[Paragraph-level] PMCID: PMC4675689 Section: RESULTS PassageIndex: 5

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: D835E/N | Summary: The D835E/N mutations are predicted to preserve hydrogen bonding interactions that maintain the structural integrity of the protein, suggesting an alteration in molecular function related to inhibitor binding. Evidence Type: Oncogenic | Mutation: D835E/N | Summary: The D835E/N mutations contribute to tumor development by preserving the DFG-out conformation, which is associated with sensitivity to type II inhibitors, indicating a role in cancer progression.

Gene→Variant (gene-first): 2322:D835 2322:D835E/N

Genes: 2322

Variants: D835 D835E/N

[Paragraph-level] PMCID: PMC4675689 Section: RESULTS PassageIndex: 2

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: D835 | Summary: The D835 mutation is associated with resistance to FLT3 tyrosine kinase inhibitors (TKIs), indicating its predictive value for therapy response. Evidence Type: Oncogenic | Mutation: D835 | Summary: D835 substitutions are reported to contribute to FLT3 TKI resistance, suggesting their role in tumor development and progression. Evidence Type: Predictive | Mutation: D835V/Y/F | Summary: The D835V/Y/F mutations are linked to a high degree of resistance to type II FLT3 inhibitors, indicating their predictive value for therapy response. Evidence Type: Oncogenic | Mutation: D835V/Y/F | Summary: The D835V/Y/F mutations are implicated in clinical resistance to FLT3 inhibitors, supporting their oncogenic potential. Evidence Type: Predictive | Mutation: D835H | Summary: The D835H mutation is associated with intermediate resistance to sorafenib, indicating its predictive value for therapy response. Evidence Type: Oncogenic | Mutation: D835H | Summary: The D835H mutation has been observed in clinical resistance to sorafenib, suggesting its role in tumor progression. Evidence Type: Predictive | Mutation: D835A/E/G/N | Summary: The D835A/E/G/N mutations conferred the least degree of resistance to type II inhibitors, indicating their predictive value for therapy response. Evidence Type: Oncogenic | Mutation: D835A/E/G/N | Summary: The D835A/E/G/N mutations are associated with lower resistance to FLT3 inhibitors, suggesting their involvement in tumor behavior.

Gene→Variant (gene-first): 2322:D835 2322:D835A/E 2322:D835H 2322:D835V/Y

Genes: 2322

Variants: D835 D835A/E D835H D835V/Y

[Paragraph-level] PMCID: PMC4411002 Section: RESULTS PassageIndex: 16

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: c.3140 A>G [p.H1047R] | Summary: The c.3140 A>G [p.H1047R] mutation was identified in primary fibroblasts and is associated with tumor development in patients with FAO. Evidence Type: Oncogenic | Mutation: c.3140 A>T [p.H1047L] | Summary: The c.3140 A>T [p.H1047L] mutation was detected in a tissue biopsy and is implicated in tumor progression in the context of FAO.

Gene→Variant (gene-first): 5294:3140 A>T 5290:c.3140 A>G 5290:c.3140 A>T 5290:p.H1047L 5290:p.H1047R

Genes: 5294 5290

Variants: 3140 A>T c.3140 A>G c.3140 A>T p.H1047L p.H1047R

[Paragraph-level] PMCID: PMC4411002 Section: RESULTS PassageIndex: 15

Evidence Type(s): Diagnostic, Oncogenic

Summary: Evidence Type: Diagnostic | Mutation: c.241 G>A; p.E81K | Summary: The presence of the c.241 G>A [p.E81K] mutation was confirmed in biopsies, indicating its use in defining or confirming a disease or subtype. Evidence Type: Oncogenic | Mutation: c.241 G>A; p.E81K | Summary: The mutation is present in tumor biopsies, suggesting it contributes to tumor development or progression.

Gene→Variant (gene-first): 5290:c.241 G>A 5290:p.E81K

Genes: 5290

Variants: c.241 G>A p.E81K

[Paragraph-level] PMCID: PMC4411002 Section: RESULTS PassageIndex: 12

Evidence Type(s): Oncogenic, Predisposing

Summary: Evidence Type: Oncogenic | Mutation: c.241 G>A; p.E81K | Summary: The mutation c.241 G>A [p.E81K] in PIK3CA is identified as a somatic variant contributing to tumor development or progression, as it was detected in various tissues of the proband but not in the blood or parents, indicating its potential role in cancer. Evidence Type: Predisposing | Mutation: c.241 G>A; p.E81K | Summary: The presence of the c.241 G>A [p.E81K] mutation in the proband's tissues, along with its absence in the blood and parents, suggests it may confer inherited risk for disease, indicating a possible germline component.

Gene→Variant (gene-first): 5290:c.241 G>A 5290:p.E81K

Genes: 5290

Variants: c.241 G>A p.E81K

[Paragraph-level] PMCID: PMC12221223 Section: RESULTS PassageIndex: 3

Evidence Type(s): Diagnostic, Oncogenic

Summary: Evidence Type: Diagnostic | Mutation: C>T | Summary: The C>T mutation is characterized as a well-established feature defining cutaneous melanoma, indicating its role in classifying the disease. Evidence Type: Oncogenic | Mutation: C>T | Summary: The C>T mutation contributes to tumor development in the context of NF1Mut melanomas, supporting its classification as an oncogenic variant.

Gene→Variant (gene-first): 4763:C>T

Genes: 4763

Variants: C>T

[Paragraph-level] PMCID: PMC8077124 Section: ABSTRACT PassageIndex: 10

Evidence Type(s): Oncogenic, Predictive

Summary: Evidence Type: Oncogenic | Mutation: p.K656E | Summary: The FGFR1 p.K656E mutation is described as activating and transforming, indicating its contribution to tumor development or progression. Evidence Type: Predictive | Mutation: p.V561M | Summary: The FGFR1 p.V561M mutation is noted to impart resistance to FGFR inhibitors, suggesting its correlation with treatment response.

Gene→Variant (gene-first): 2260:p.K656E 2260:p.V561M

Genes: 2260

Variants: p.K656E p.V561M

[Paragraph-level] PMCID: PMC8077124 Section: ABSTRACT PassageIndex: 7

Evidence Type(s): Oncogenic, Predictive

Summary: Evidence Type: Oncogenic | Mutation: p.K656E | Summary: The p.K656E mutation is described as a known hotspot mutation that is both activating and transforming, indicating its role in tumor development. Evidence Type: Predictive | Mutation: p.V561M | Summary: The p.V561M mutation is characterized as a gatekeeper mutation that imparts resistance to FGFR inhibitors, suggesting its relevance in therapy response.

Gene→Variant (gene-first): 2260:p.K656E 2260:p.V561M

Genes: 2260

Variants: p.K656E p.V561M

[Paragraph-level] PMCID: PMC4741605 Section: RESULTS PassageIndex: 20

Evidence Type(s): Predictive, Prognostic, Oncogenic

Summary: Evidence Type: Predictive | Mutation: D835Y | Summary: The D835Y mutation is associated with the patient's response to chemotherapy treatment, indicating its relevance in predicting treatment outcomes. Evidence Type: Prognostic | Mutation: D835Y | Summary: The increase in the D835Y mutated clone at relapse suggests that this mutation may correlate with disease outcome independent of therapy, highlighting its prognostic significance. Evidence Type: Oncogenic | Mutation: D835Y | Summary: The D835Y mutation contributes to tumor development or progression, as indicated by its increase in frequency at relapse.

Gene→Variant (gene-first): 2322:D835Y

Genes: 2322

Variants: D835Y

[Paragraph-level] PMCID: PMC4741605 Section: RESULTS PassageIndex: 19

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: D835Y | Summary: The D835Y mutation was successfully inhibited by treatment, indicating a correlation with treatment response. Evidence Type: Oncogenic | Mutation: D835Y | Summary: The presence of the D835Y mutation is associated with tumor behavior, as it is part of a clone that is monitored during disease progression.

Gene→Variant (gene-first): 2322:D835Y

Genes: 2322

Variants: D835Y

[Paragraph-level] PMCID: PMC4741605 Section: RESULTS PassageIndex: 17

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: D835Y | Summary: The D835Y mutation is associated with the presence of small TKD mutated clones in the patient, indicating its contribution to tumor development or progression. Evidence Type: Oncogenic | Mutation: D839G | Summary: The D839G mutation is also part of the small TKD mutated clones observed in the patient, suggesting its role in tumor development or progression.

Gene→Variant (gene-first): 2322:D835Y 2322:D839G

Genes: 2322

Variants: D835Y D839G

[Paragraph-level] PMCID: PMC9398166 Section: ABSTRACT PassageIndex: 2

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: G1202R | Summary: The G1202R mutation is described as a major resistance mechanism to first-generation ALK inhibitors and contributes to tumor development, as evidenced by its role in ALK compound mutation-dependent xenograft models. Evidence Type: Oncogenic | Mutation: L1196M | Summary: The L1196M mutation is identified as a significant resistance mechanism to first-generation ALK inhibitors, indicating its contribution to tumor development in the context of ALK mutations.

Gene→Variant (gene-first): 238:G1202R 238:L1196M

Genes: 238

Variants: G1202R L1196M

[Paragraph-level] PMCID: PMC9398166 Section: RESULTS PassageIndex: 9

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: G1202R | Summary: The G1202R mutation is associated with resistance to lorlatinib, as indicated by the higher IC50 values, suggesting that it correlates with treatment response to TPX-0131. Evidence Type: Predictive | Mutation: L1196M | Summary: The L1196M mutation, when combined with G1202R, shows a similar resistance pattern to lorlatinib, indicating its role in treatment response to TPX-0131. Evidence Type: Predictive | Mutation: L1198F | Summary: The L1198F mutation, in conjunction with G1202R, demonstrates resistance to lorlatinib, highlighting its predictive value for treatment response to TPX-0131. Evidence Type: Oncogenic | Mutation: G1202R | Summary: The G1202R mutation is part of the EML4-ALK oncogenic fusion proteins, contributing to tumor development and progression. Evidence Type: Oncogenic | Mutation: L1196M | Summary: The L1196M mutation is included in the EML4-ALK oncogenic fusion context, indicating its contribution to tumor development. Evidence Type: Oncogenic | Mutation: L1198F | Summary: The L1198F mutation is also part of the EML4-ALK oncogenic fusion proteins, suggesting its role in tumor progression.

Gene→Variant (gene-first): 238:G1202R 238:L1196M 238:L1198 238:L1198F

Genes: 238

Variants: G1202R L1196M L1198 L1198F

[Paragraph-level] PMCID: PMC9398166 Section: RESULTS PassageIndex: 7

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: G1202R | Summary: The G1202R mutation is described as a solvent front mutation that contributes to tumor development, as TPX-0131 demonstrated the most potent inhibition of cell proliferation against cells harboring this mutation. Evidence Type: Oncogenic | Mutation: L1196M | Summary: The L1196M mutation is identified as a gatekeeper mutation that contributes to tumor development, with TPX-0131 showing significantly greater potency against this mutation compared to previous ALK inhibitors. Evidence Type: Oncogenic | Mutation: L1198F | Summary: The L1198F mutation is characterized as a hinge region mutation that contributes to tumor development, with TPX-0131 exhibiting high potency against this mutation. Evidence Type: Oncogenic | Mutation: G1269A | Summary: The G1269A mutation is noted as a resistance mutation, with TPX-0131 showing moderate potency against cells harboring this mutation. Evidence Type: Functional | Mutation: I1171N/S/T | Summary: The I1171N/S/T mutations are described in the context of their impact on the potency of TPX-0131, indicating that these mutations alter the molecular function related to drug response.

Gene→Variant (gene-first): 238:C1156Y 238:G1202R 238:G1269A 238:G1269S 238:I1171N 238:I1171N/S 238:L1196M 238:L1198F 238:L1204V 238:S/T

Genes: 238

Variants: C1156Y G1202R G1269A G1269S I1171N I1171N/S L1196M L1198F L1204V S/T

[Paragraph-level] PMCID: PMC9398166 Section: RESULTS PassageIndex: 3

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: G1202 | Summary: The G1202 mutation is associated with resistance to second-generation ALK inhibitors, indicating its relevance in predicting treatment response and resistance to specific therapies. Evidence Type: Oncogenic | Mutation: G1202 | Summary: The G1202 mutation contributes to tumor development by obstructing binding of ALK inhibitors, which is characteristic of oncogenic behavior in cancer progression.

Gene→Variant (gene-first): 238:G1202

Genes: 238

Variants: G1202

[Paragraph-level] PMCID: PMC5820258 Section: RESULTS PassageIndex: 16

Evidence Type(s): Predictive, Oncogenic, Functional

Summary: Evidence Type: Predictive | Mutation: BRAFV600E | Summary: The BRAFV600E mutation is associated with venetoclax resistance, indicating a correlation with treatment response. Evidence Type: Oncogenic | Mutation: BRAFV600E | Summary: The BRAFV600E mutation contributes to tumor development and progression, as evidenced by its role in inducing venetoclax resistance in cell lines. Evidence Type: Functional | Mutation: p.W110 | Summary: The p.W110 mutation in CDKN2A/B is a nonsense mutation that likely alters the molecular function of the gene, contributing to cancer-related processes.

Gene→Variant (gene-first): 673:BRAFV600E 673:p.V600E 7157:p.W110*

Genes: 673 7157

Variants: BRAFV600E p.V600E p.W110*

[Paragraph-level] PMCID: PMC5820258 Section: RESULTS PassageIndex: 14

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: c.1996A > C | Summary: The SF3B1 mutation c.1996A > C was identified in cancer cell subclones that evolved during venetoclax exposure, indicating its contribution to tumor development and progression. Evidence Type: Oncogenic | Mutation: c.1997A > C | Summary: The SF3B1 mutation c.1997A > C was found in subclones that emerged during treatment with venetoclax, suggesting its role in tumor development and progression. Evidence Type: Oncogenic | Mutation: p.K666Q | Summary: The mutation p.K666Q was detected in small subclones before treatment and evolved during venetoclax therapy, indicating its involvement in oncogenic processes. Evidence Type: Oncogenic | Mutation: p.K666T | Summary: The mutation p.K666T was present in subclones that evolved during venetoclax exposure, supporting its role in tumor development and progression.

Gene→Variant (gene-first): 23451:c.1996A > C 23451:c.1997A > C 23451:p.K666Q 23451:p.K666T

Genes: 23451

Variants: c.1996A > C c.1997A > C p.K666Q p.K666T

[Paragraph-level] PMCID: PMC5820258 Section: RESULTS PassageIndex: 13

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: p.K601E | Summary: The mutation p.K601E in BRAF is associated with tumor development and progression, as it was retained in the subclone that emerged during venetoclax therapy. Evidence Type: Oncogenic | Mutation: p.S321fs | Summary: The mutation p.S321fs in MLL3 is implicated in tumor development, as it was present in the subclone that persisted through treatment. Evidence Type: Oncogenic | Mutation: p.Q547fs | Summary: The frameshift deletion p.Q547fs in BIRC3 is recognized as a driver mutation in CLL, contributing to tumorigenesis.

Gene→Variant (gene-first): 673:p.K601E 330:p.Q547fs 58508:p.S321fs

Genes: 673 330 58508

Variants: p.K601E p.Q547fs p.S321fs

[Paragraph-level] PMCID: PMC5820258 Section: RESULTS PassageIndex: 12

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: p.E46K | Summary: The p.E46K mutation in BTG1 is associated with the development of a dominant clone at relapse, suggesting its involvement in resistance to venetoclax treatment. Evidence Type: Oncogenic | Mutation: p.E46K | Summary: The p.E46K mutation contributes to tumor evolution and is selected as a dominant clone, indicating its role in tumor progression. Evidence Type: Oncogenic | Mutation: p.Q36H | Summary: The p.Q36H mutation is part of a branch observed only in the relapse sample, suggesting its contribution to tumor evolution and progression.

Gene→Variant (gene-first): 7157:p.E46K 694:p.Q36H

Genes: 7157 694

Variants: p.E46K p.Q36H

[Paragraph-level] PMCID: PMC5820258 Section: RESULTS PassageIndex: 10

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: p.Q36H | Summary: The BTG1 missense mutation p.Q36H may contribute to tumor development or progression in CLL cells under targeted BCL2-inhibition, providing a survival advantage. Evidence Type: Oncogenic | Mutation: p.E46K | Summary: The BTG1 missense mutation p.E46K may contribute to tumor development or progression in CLL cells under targeted BCL2-inhibition, providing a survival advantage.

Gene→Variant (gene-first): 7157:p.E46K 694:p.Q36H

Genes: 7157 694

Variants: p.E46K p.Q36H

[Paragraph-level] PMCID: PMC5820258 Section: RESULTS PassageIndex: 8

Evidence Type(s): Oncogenic, Predictive

Summary: Evidence Type: Oncogenic | Mutation: p.K601E | Summary: The BRAF p.K601E mutation is described as oncogenic and contributes to tumor development, making it a target for therapies such as MEK inhibitors. Evidence Type: Predictive | Mutation: p.K601E | Summary: The BRAF p.K601E mutation correlates with response to venetoclax therapy, indicating its potential role in guiding treatment options.

Gene→Variant (gene-first): 673:p.K601E

Genes: 673

Variants: p.K601E

[Paragraph-level] PMCID: PMC10527017 Section: RESULTS PassageIndex: 25

Evidence Type(s): Oncogenic, Diagnostic

Summary: Evidence Type: Oncogenic | Mutation: H1047R | Summary: The H1047R mutation in PIK3CA is associated with tumor development and progression, as indicated by its presence in samples from patients with specific cancer subtypes. Evidence Type: Diagnostic | Mutation: H1047R | Summary: The H1047R mutation is used to classify tumors into specific subtypes, such as Luminal A and B, based on PAM50 classification, indicating its role in defining disease characteristics.

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

Genes: 5290

Variants: H1047R

[Paragraph-level] PMCID: PMC10527017 Section: RESULTS PassageIndex: 22

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: V777L | Summary: The HER2 V777L mutation contributes to tumor development and progression by amplifying the signaling transduction cascade, leading to increased oncogene expression and tumorigenesis.

Gene→Variant (gene-first): 2064:V777L

Genes: 2064

Variants: V777L

[Paragraph-level] PMCID: PMC10527017 Section: RESULTS PassageIndex: 20

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: V777L | Summary: The HER2 V777L mutation is implicated in contributing to tumor development or progression, as it affects distinct expression programs in the context of cancer.

Gene→Variant (gene-first): 2064:V777L

Genes: 2064

Variants: V777L

[Paragraph-level] PMCID: PMC10527017 Section: RESULTS PassageIndex: 18

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: V777L | Summary: The HER2 V777L mutation is associated with altered molecular function as indicated by the changes in phosphorylation levels of various proteins in breast cancer organoids, suggesting a role in signal transduction pathways. Evidence Type: Oncogenic | Mutation: V777L | Summary: The HER2 V777L mutation contributes to tumor development or progression, as evidenced by its presence in the HP mice tumor model and the associated changes in cellular markers related to cancer.

Gene→Variant (gene-first): 2064:V777L

Genes: 2064

Variants: V777L

[Paragraph-level] PMCID: PMC10527017 Section: RESULTS PassageIndex: 17

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: V777L | Summary: The HER2V777L mutation is associated with promoting cell proliferation and enhancing the cell cycle process, contributing to tumor development in the context of breast cancer. Evidence Type: Functional | Mutation: V777L | Summary: The HER2V777L mutation alters molecular function by enhancing the phosphorylation of key proteins involved in cell cycle regulation, indicating a role in the signaling pathways that drive cancer progression.

Gene→Variant (gene-first): 2064:V777L

Genes: 2064

Variants: V777L

[Paragraph-level] PMCID: PMC10527017 Section: RESULTS PassageIndex: 15

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: G776insYVMA | Summary: The G776insYVMA mutation is associated with tumor development as it is part of a HER2 activating mutation in a breast cancer model. Evidence Type: Oncogenic | Mutation: V777L | Summary: The V777L mutation is linked to tumor progression in the context of HER2 activation, as demonstrated in the breast cancer PDX model.

Gene→Variant (gene-first): 2064:G776insYVMA 2064:V777L

Genes: 2064

Variants: G776insYVMA V777L

[Paragraph-level] PMCID: PMC10527017 Section: RESULTS PassageIndex: 9

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: V777L | Summary: The HER2V777L mutation is implicated in the development of metastatic breast cancer, as evidenced by the observed lung metastasis in transgenic mice expressing this mutation. Evidence Type: Functional | Mutation: V777L | Summary: The HER2V777L mutation alters the invasive phenotype of breast tumor cells, as indicated by the metastatic behavior observed in vitro and in vivo.

Gene→Variant (gene-first): 2064:V777L

Genes: 2064

Variants: V777L

[Paragraph-level] PMCID: PMC10527017 Section: RESULTS PassageIndex: 8

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: V777L | Summary: The V777L mutation is associated with lung metastases in transgenic mice, indicating its contribution to tumor development or progression.

Gene→Variant (gene-first): 2064:V777L

Genes: 2064

Variants: V777L

[Paragraph-level] PMCID: PMC10527017 Section: RESULTS PassageIndex: 7

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: V777L | Summary: The HER2V777L mutation is associated with enhanced cellular migration and invasion in breast organoids, indicating its role in promoting cancer cell behavior and contributing to tumor progression.

Gene→Variant (gene-first): 2064:V777L

Genes: 2064

Variants: V777L

[Paragraph-level] PMCID: PMC10527017 Section: RESULTS PassageIndex: 3

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: H1047R | Summary: The PIK3CA H1047R mutation is described as a gain-of-function allele and activating mutation commonly found in human breast cancers, indicating its role in tumor development. Evidence Type: Oncogenic | Mutation: V777L | Summary: The HER2 V777L mutation is part of a transgenic model that expresses this variant, suggesting its involvement in tumor progression.

Gene→Variant (gene-first): 5290:H1047R 2064:V777L

Genes: 5290 2064

Variants: H1047R V777L

[Paragraph-level] PMCID: PMC10527017 Section: RESULTS PassageIndex: 2

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: V777L | Summary: The HER2 V777L mutation is associated with tumor formation in mice, indicating its role in tumor development and progression.

Gene→Variant (gene-first): 2064:V777L

Genes: 2064

Variants: V777L

[Paragraph-level] PMCID: PMC5792548 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: T790M | Summary: The EGFR T790M mutation is associated with resistance to the standard treatment osimeritinib in non-small cell lung cancer, indicating its predictive role in therapy response. Evidence Type: Oncogenic | Mutation: T790M | Summary: The EGFR T790M mutation contributes to tumor development and progression, as it is implicated in acquired resistance to EGFR tyrosine kinase inhibitors.

Gene→Variant (gene-first): 1956:T790M

Genes: 1956

Variants: T790M

[Paragraph-level] PMCID: PMC7294133 Section: RESULTS PassageIndex: 15

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: V871I | Summary: The EPHB4-V871I variant is associated with increased expression levels of downstream target genes and enhanced phosphorylation of the ERK1-2 pathway, indicating an alteration in molecular function. Evidence Type: Oncogenic | Mutation: V871I | Summary: The EPHB4-V871I variant contributes to tumor development or progression as suggested by its impact on downstream signaling pathways and gene expression.

Gene→Variant (gene-first): 2050:V871I

Genes: 2050

Variants: V871I

[Paragraph-level] PMCID: PMC7294133 Section: RESULTS PassageIndex: 11

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: V871I | Summary: The EPHB4-V871I variant demonstrates increased migration properties in wound-healing experiments, indicating an alteration in molecular function related to cell migration. Evidence Type: Oncogenic | Mutation: V871I | Summary: The increased migration potential of EPHB4-V871I suggests that this somatic variant may contribute to tumor development or progression by enhancing cell motility.

Gene→Variant (gene-first): 2050:V871I

Genes: 2050

Variants: V871I

[Paragraph-level] PMCID: PMC7294133 Section: RESULTS PassageIndex: 10

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: V871I | Summary: The V871I mutation in EPHB4 is associated with altered cellular proliferation, as indicated by increased propagation rates in cells overexpressing this variant compared to controls. Evidence Type: Oncogenic | Mutation: V871I | Summary: The V871I mutation in EPHB4 contributes to tumor development and progression, as suggested by its involvement in increased proliferation rates in cancer cell lines.

Gene→Variant (gene-first): 2050:V871I

Genes: 2050

Variants: V871I

[Paragraph-level] PMCID: PMC7294133 Section: RESULTS PassageIndex: 4

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: V871I | Summary: The variant V871I in the kinase domain of EPHB4 is associated with a high pathogenic score, indicating its contribution to tumor development or progression.

Gene→Variant (gene-first): 4613:A417S 2050:V871I

Genes: 4613 2050

Variants: A417S V871I

[Paragraph-level] PMCID: PMC7294133 Section: RESULTS PassageIndex: 3

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: F1174L | Summary: The F1174L mutation in the ALK gene is identified as a somatic variant that is frequently observed in neuroblastoma, suggesting its contribution to tumor development or progression.

Gene→Variant (gene-first): 238:F1174L

Genes: 238

Variants: F1174L

[Paragraph-level] PMCID: PMC2837563 Section: RESULTS PassageIndex: 9

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: G12V | Summary: The G12V mutation in K-Ras was associated with abundant foci formation in NIH3T3 cells, indicating its contribution to tumor development. Evidence Type: Oncogenic | Mutation: G12D | Summary: The G12D mutation in K-Ras demonstrated significant focus formation in NIH3T3 cells, suggesting its role in tumor progression. Evidence Type: Oncogenic | Mutation: G13D | Summary: The G13D mutation in K-Ras was linked to significant focus formation in NIH3T3 cells, indicating its oncogenic potential. Evidence Type: Oncogenic | Mutation: Q61H | Summary: The Q61H mutation in K-Ras showed focus formation in NIH3T3 cells, although it had a lesser transforming potential compared to codon 12 mutations. Evidence Type: Oncogenic | Mutation: L19F | Summary: The L19F mutation in K-Ras resulted in low but consistent numbers of isolated foci in NIH3T3 cells, suggesting its involvement in tumor development. Evidence Type: Oncogenic | Mutation: K117N | Summary: The K117N mutation in K-Ras was associated with significant focus formation in NIH3T3 cells, indicating its contribution to tumor progression. Evidence Type: Oncogenic | Mutation: A146T | Summary: The A146T mutation in K-Ras led to significant focus formation in NIH3T3 cells, suggesting its role in tumor development. Evidence Type: Oncogenic | Mutation: R164Q | Summary: The R164Q mutation in K-Ras was phenotypically equivalent to wild-type K-Ras with no evidence of foci formation, indicating it does not contribute to tumor development.

Gene→Variant (gene-first): 3845:A146T 3845:G12D 3845:G12V 3845:G13D 3845:K117N 3845:L19F 3845:Q61H 3845:R164Q

Genes: 3845

Variants: A146T G12D G12V G13D K117N L19F Q61H R164Q

[Paragraph-level] PMCID: PMC2837563 Section: RESULTS PassageIndex: 4

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: A to C (Lys to Asn at codon 117) | Summary: This K-Ras mutation is associated with tumor development or progression in colorectal tumors. Evidence Type: Oncogenic | Mutation: G to A (Ala to Thr at codon 146) | Summary: This K-Ras mutation contributes to tumor development or progression in colorectal tumors. Evidence Type: Oncogenic | Mutation: G to A (Arg to Gln at codon 164) | Summary: This K-Ras mutation is implicated in tumor development or progression in colorectal tumors. Evidence Type: Oncogenic | Mutation: V600E | Summary: The B-Raf V600E mutation is known to contribute to tumor development or progression in colorectal tumors.

Gene→Variant (gene-first): 3845:A to C 3845:Ala to Thr 3845:Arg to Gln 3845:C to T 3845:G to A 3845:Lys to Asn 673:V600E 3845:aspartic acid residue at codon 173

Genes: 3845 673

Variants: A to C Ala to Thr Arg to Gln C to T G to A Lys to Asn V600E aspartic acid residue at codon 173

[Paragraph-level] PMCID: PMC2837563 Section: RESULTS PassageIndex: 3

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: G57T | Summary: The G57T mutation is associated with tumor development or progression as it was found in a colorectal tumor. Evidence Type: Oncogenic | Mutation: Leu19Phe | Summary: The Leu19Phe mutation is associated with tumor development or progression as it was found in a colorectal tumor. Evidence Type: Oncogenic | Mutation: V600E | Summary: The V600E mutation is associated with tumor development or progression as it was found in a colorectal tumor.

Gene→Variant (gene-first): 673:G57T 3845:Leu19Phe 673:V600E

Genes: 673 3845

Variants: G57T Leu19Phe V600E

[Paragraph-level] PMCID: PMC9441062 Section: RESULTS PassageIndex: 4

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: G719C | Summary: The G719C mutation is part of a double-mutant patient cohort, indicating its contribution to tumor development in the context of acquired RET fusions. Evidence Type: Oncogenic | Mutation: L858R | Summary: The L858R mutation is identified in a significant proportion of patients, suggesting its role in tumor development in NSCLC. Evidence Type: Oncogenic | Mutation: S768I | Summary: The S768I mutation is included in a double-mutant patient cohort, indicating its contribution to tumor development in the context of acquired RET fusions.

Gene→Variant (gene-first): 1956:G719C 1956:L858R 1956:S768I

Genes: 1956

Variants: G719C L858R S768I

[Paragraph-level] PMCID: PMC10618648 Section: RESULTS PassageIndex: 20

Evidence Type(s): Oncogenic, Predictive

Summary: Evidence Type: Oncogenic | Mutation: T733I | Summary: The ERBB2 T733I mutation is noted to be weakly transforming in a gastroesophageal PDX model, indicating its contribution to tumor development. Evidence Type: Predictive | Mutation: T733I | Summary: The T733I mutation is associated with resistance to lapatinib and sensitivity to adavosertib, suggesting its role in predicting treatment response.

Gene→Variant (gene-first): 2064:T733I

Genes: 2064

Variants: T733I

[Paragraph-level] PMCID: PMC10618648 Section: RESULTS PassageIndex: 16

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: V777L | Summary: The V777L mutation in the ERBB2 gene is identified in the tyrosine kinase domain, suggesting its contribution to tumor development or progression. Evidence Type: Oncogenic | Mutation: G778A | Summary: The G778A mutation in the ERBB2 gene is identified in the tyrosine kinase domain, indicating its role in tumor development or progression.

Gene→Variant (gene-first): 2064:G778A 2064:V777L

Genes: 2064

Variants: G778A V777L

[Paragraph-level] PMCID: PMC3727232 Section: RESULTS PassageIndex: 11

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: p.K27M | Summary: The H3F3A:p.K27M mutation is associated with tumor development in certain gliomas, indicating its role as a cancer-driving variant. Evidence Type: Oncogenic | Mutation: p.V600E | Summary: The BRAF:p.V600E mutation is frequently detected in pleomorphic xanthoastrocytomas and other gliomas, contributing to tumor progression.

Gene→Variant (gene-first): 3021:p.K27M 673:p.V600E

Genes: 3021 673

Variants: p.K27M p.V600E

[Paragraph-level] PMCID: PMC3727232 Section: RESULTS PassageIndex: 6

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: p.R132H | Summary: The IDH1 mutation p.R132H is associated with tumor development or progression in the context of oligodendroglioma. Evidence Type: Functional | Mutation: p.V676fs | Summary: The CIC mutation p.V676fs alters molecular or biochemical function, contributing to the tumor's genetic profile. Evidence Type: Functional | Mutation: p.S726R | Summary: The CIC mutation p.S726R alters molecular or biochemical function, contributing to the tumor's genetic profile. Evidence Type: Functional | Mutation: p.D1722V | Summary: The CHD2 mutation p.D1722V alters molecular or biochemical function, contributing to the tumor's genetic profile. Evidence Type: Functional | Mutation: p.P101L | Summary: The STYK1 mutation p.P101L alters molecular or biochemical function, contributing to the tumor's genetic profile.

Gene→Variant (gene-first): 1106:p.D1722V 1029:p.P101L 3417:p.R132H 23152:p.S726R 23152:p.V676fs

Genes: 1106 1029 3417 23152

Variants: p.D1722V p.P101L p.R132H p.S726R p.V676fs

[Paragraph-level] PMCID: PMC3727232 Section: RESULTS PassageIndex: 5

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: p.K27M | Summary: The H3F3A:p.K27M mutation is associated with tumor development in supratentorial diffuse astrocytomas, indicating its role as a somatic variant contributing to oncogenesis. Evidence Type: Oncogenic | Mutation: p.V600E | Summary: The BRAF:p.V600E mutation is frequently observed in pleomorphic xanthoastrocytomas, suggesting its contribution to tumor development and progression as a somatic variant.

Gene→Variant (gene-first): 3021:p.K27M 673:p.V600E

Genes: 3021 673

Variants: p.K27M p.V600E

[Paragraph-level] PMCID: PMC6938308 Section: ABSTRACT PassageIndex: 6

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: G12D | Summary: The G12D mutation is a somatic variant that contributes to tumor development or progression, as indicated by its presence in specimens with confirmed mutations. Evidence Type: Oncogenic | Mutation: G12V | Summary: The G12V mutation is a somatic variant that contributes to tumor development or progression, as indicated by its presence in specimens with confirmed mutations. Evidence Type: Oncogenic | Mutation: V600E | Summary: The V600E mutation is a somatic variant that contributes to tumor development or progression, as indicated by its presence in specimens with confirmed mutations. Evidence Type: Oncogenic | Mutation: Q636X | Summary: The Q636X mutation is a somatic variant that contributes to tumor development or progression, as indicated by its presence in specimens with confirmed mutations.

Gene→Variant (gene-first): 3845:G12D 3845:G12V 673:Q636X 673:V600E

Genes: 3845 673

Variants: G12D G12V Q636X V600E

[Paragraph-level] PMCID: PMC7820803 Section: RESULTS PassageIndex: 13

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: p.Ala636Pro | Summary: The variant p.Ala636Pro is associated with a significant depletion of deleterious scores in a functional assay, indicating that it alters molecular or biochemical function. Evidence Type: Oncogenic | Mutation: p.Ala636Pro | Summary: The variant p.Ala636Pro is implicated in the context of bi-allelic MMR loss, which is known to contribute to tumor development in pediatric-onset cancer syndromes such as Lynch syndrome.

Gene→Variant (gene-first): 4436:p.Ala636Pro

Genes: 4436

Variants: p.Ala636Pro

[Paragraph-level] PMCID: PMC7820803 Section: RESULTS PassageIndex: 7

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: p.Ala636Pro | Summary: The mutation p.Ala636Pro in MSH2 is associated with MMR deficiency and contributes to tumor development, as indicated by its enrichment in selected cell pools under selective conditions.

Gene→Variant (gene-first): 4436:p.Ala636Pro

Genes: 4436

Variants: p.Ala636Pro

[Paragraph-level] PMCID: PMC7820803 Section: RESULTS PassageIndex: 4

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: p.Ala636Pro | Summary: The p.Ala636Pro mutant variant of MSH2 was shown to restore 6-TG sensitivity in a functional assay, indicating that it alters the molecular function of the MMR machinery. Evidence Type: Oncogenic | Mutation: p.Ala636Pro | Summary: The enrichment of barcodes linked to the pathogenic variant p.Ala636Pro in mixed cultures suggests that this somatic variant contributes to tumor development or progression by affecting MMR function.

Gene→Variant (gene-first): 4436:p.Ala636Pro

Genes: 4436

Variants: p.Ala636Pro

[Paragraph-level] PMCID: PMC7820803 Section: RESULTS PassageIndex: 3

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: p.Ala636Pro | Summary: The p.Ala636Pro variant is associated with a destabilizing effect on MSH2 protein expression, indicating an alteration in molecular function. Evidence Type: Oncogenic | Mutation: p.Ala636Pro | Summary: The p.Ala636Pro variant is described as a pathogenic founder allele, suggesting its contribution to tumor development or progression.

Gene→Variant (gene-first): 4436:p.Ala636Pro

Genes: 4436

Variants: p.Ala636Pro

[Paragraph-level] PMCID: PMC3383766 Section: RESULTS PassageIndex: 21

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: V777L | Summary: The V777L mutation in ERBB2 is associated with tumor development, particularly in the context of gefitinib-activating mutations in lung cancer. Evidence Type: Oncogenic | Mutation: A829V | Summary: The A829V mutation in DDR1 is implicated in tumor development and progression. Evidence Type: Oncogenic | Mutation: R611C | Summary: The R611C mutation in DDR1 contributes to tumor development. Evidence Type: Oncogenic | Mutation: E583D | Summary: The E583D mutation in DDR2 is associated with oncogenic activity. Evidence Type: Oncogenic | Mutation: D735H | Summary: The D735H mutation in CSF1R is linked to tumor progression. Evidence Type: Oncogenic | Mutation: M875L | Summary: The M875L mutation in CSF1R contributes to tumor development. Evidence Type: Oncogenic | Mutation: E924K | Summary: The E924K mutation in PDGFRA is associated with oncogenic behavior. Evidence Type: Functional | Mutation: C77F | Summary: The C77F mutation in AKT1 alters molecular function. Evidence Type: Functional | Mutation: S11F | Summary: The S11F mutation in AKT2 affects molecular function. Evidence Type: Functional | Mutation: S375F | Summary: The S375F mutation in RPS6KB1 alters biochemical function.

Gene→Variant (gene-first): 780:A829V 207:C77F 405:D735H 3084:E583D 2048:E924K 5156:M875L 780:R611C 208:S11F 3169:S375F 2064:V777L

Genes: 780 207 405 3084 2048 5156 208 3169 2064

Variants: A829V C77F D735H E583D E924K M875L R611C S11F S375F V777L

[Paragraph-level] PMCID: PMC3383766 Section: RESULTS PassageIndex: 10

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: M294K | Summary: The M294K mutation in GATA3 is associated with functional inactivation, as indicated by the presence of truncation events and other mutations in the gene. Evidence Type: Oncogenic | Mutation: M294K | Summary: The recurrent M294K mutation in GATA3 suggests a role in tumor development, reinforcing the conclusion that GATA3 acts as a tumor suppressor.

Gene→Variant (gene-first): 2625:M294K

Genes: 2625

Variants: M294K

[Paragraph-level] PMCID: PMC3383766 Section: RESULTS PassageIndex: 8

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: R251H | Summary: The R251H mutation in AGTR2 is associated with angiotensin signaling, which intersects with pathways implicated in tissue fibrosis, suggesting a role in tumor development or progression. Evidence Type: Oncogenic | Mutation: V184I | Summary: The V184I mutation in AGTR2 is linked to angiotensin signaling, indicating its potential contribution to tumor development or progression.

Gene→Variant (gene-first): 186:R251H 186:V184I

Genes: 186

Variants: R251H V184I

[Paragraph-level] PMCID: PMC3383766 Section: RESULTS PassageIndex: 7

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: G168E | Summary: The G168E mutation in RUNX1 is implicated in tumor development and progression, particularly in the M2 subtype of AML. Evidence Type: Oncogenic | Mutation: R166Q | Summary: The R166Q mutation in RUNX1 contributes to tumor development and is associated with the M2 subtype of AML. Evidence Type: Oncogenic | Mutation: R169K | Summary: The R169K mutation in RUNX1 is involved in tumor progression and is relevant to the M2 subtype of AML. Evidence Type: Oncogenic | Mutation: K700E | Summary: The K700E mutation in SF3B1 is implicated in tumor development and is associated with myelodysplastic syndromes (MDS) and chronic lymphocytic leukemia (CLL). Evidence Type: Oncogenic | Mutation: K666Q | Summary: The K666Q mutation in SF3B1 contributes to tumor development and is relevant in the context of MDS and CLL. Evidence Type: Functional | Mutation: S184L | Summary: The S184L mutation in MAP2K4 alters molecular function, likely affecting splicing and kinase pathway activation.

Gene→Variant (gene-first): 9757:G168E 23451:K666Q 23451:K700E 4216:N104S 861:R166Q 1588:R169K 51742:S184L

Genes: 9757 23451 4216 861 1588 51742

Variants: G168E K666Q K700E N104S R166Q R169K S184L

[Paragraph-level] PMCID: PMC7226056 Section: RESULTS PassageIndex: 5

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: TERT mutation | Summary: The TERT mutation is associated with glioma formation and is considered a somatic variant contributing to tumor development or progression.

Gene→Variant (gene-first): 7015:CGGA 94) in the TCGA

Genes: 7015

Variants: CGGA 94) in the TCGA

[Paragraph-level] PMCID: PMC7499606 Section: RESULTS PassageIndex: 18

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: Y220C | Summary: The TP53 Y220C missense mutation is described as a deleterious somatic mutation, indicating its contribution to tumor development or progression in the context of metastatic high-grade serous ovarian cancer.

Gene→Variant (gene-first): 7157:Y220C

Genes: 7157

Variants: Y220C

[Paragraph-level] PMCID: PMC2736831 Section: RESULTS PassageIndex: 10

Evidence Type(s): Predictive, Prognostic, Oncogenic

Summary: Evidence Type: Predictive | Mutation: V600E | Summary: The BRAF V600E mutation was associated with a lack of response to treatment compared to BRAF wild-type patients, indicating its predictive value regarding treatment resistance. Evidence Type: Prognostic | Mutation: V600E | Summary: The presence of the BRAF V600E mutation correlated with significantly shorter overall survival (OS) and a trend towards shorter progression-free survival (PFS), suggesting its prognostic implications for disease outcome. Evidence Type: Oncogenic | Mutation: V600E | Summary: The BRAF V600E mutation is implicated in tumor development or progression, as indicated by its presence in the study population and its association with poor clinical outcomes.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paragraph-level] PMCID: PMC7362646 Section: RESULTS PassageIndex: 11

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: p.R132H | Summary: The IDH1 p.R132H mutation is associated with glioma development and progression, indicating its role as a somatic variant contributing to tumorigenesis.

Gene→Variant (gene-first): 3417:p.R132H

Genes: 3417

Variants: p.R132H

[Paragraph-level] PMCID: PMC10283448 Section: ABSTRACT PassageIndex: 2

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: G2032R | Summary: The G2032R mutation is associated with resistance to crizotinib treatment in ROS1+ lung cancer, indicating its relevance in predicting treatment response. Evidence Type: Oncogenic | Mutation: G2032R | Summary: The G2032R mutation contributes to tumor progression in ROS1+ lung cancer, highlighting its role as an oncogenic variant.

Gene→Variant (gene-first): 6098:G2032R

Genes: 6098

Variants: G2032R

[Paragraph-level] PMCID: PMC7342819 Section: RESULTS PassageIndex: 2

Evidence Type(s): Oncogenic, Predisposing

Summary: Evidence Type: Oncogenic | Mutation: p.G12V | Summary: The KRAS p.G12V mutation is identified as a common driver mutation contributing to tumor development in the context of pancreatic adenocarcinoma (PAAD). Evidence Type: Predisposing | Mutation: c.3114-1G>A | Summary: The PALB2 c.3114-1G>A mutation is described as a germline mutation detected in peripheral blood cells, indicating an inherited risk for disease. Evidence Type: Oncogenic | Mutation: c.2514+1G>C | Summary: The PALB2 c.2514+1G>C mutation is noted as a somatic mutation likely contributing to tumor progression, associated with a deficiency in DNA homologous recombination.

Gene→Variant (gene-first): 79728:c.2514+1G>C 79728:c.3114-1G>A 3845:p.G12V

Genes: 79728 3845

Variants: c.2514+1G>C c.3114-1G>A p.G12V

[Paragraph-level] PMCID: PMC1702556 Section: RESULTS PassageIndex: 17

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: R108K | Summary: The R108K mutation in EGFR was associated with clinical responses to erlotinib in gliomas, suggesting a correlation with treatment sensitivity. Evidence Type: Oncogenic | Mutation: R108K | Summary: The presence of the R108K mutation in gliomas indicates its potential role in tumor development or progression, particularly in the context of EGFR amplification. Evidence Type: Predictive | Mutation: R108K | Summary: The R108K mutation was also identified in gliomas that failed EGFR kinase inhibitor therapy, indicating a possible link to treatment resistance.

Gene→Variant (gene-first): 1956:R108K

Genes: 1956

Variants: R108K

[Paragraph-level] PMCID: PMC1702556 Section: RESULTS PassageIndex: 16

Evidence Type(s): Oncogenic, Predictive

Summary: Evidence Type: Oncogenic | Mutation: L858R | Summary: The L858R mutation is suggested to play a role in gliomagenesis and contributes to tumor development as indicated by its oncogenicity in transformation assays. Evidence Type: Oncogenic | Mutation: L861Q | Summary: The L861Q mutation is implicated in gliomagenesis and is associated with tumor development, as evidenced by its oncogenic behavior in standard transformation assays. Evidence Type: Predictive | Mutation: L858R | Summary: The L858R mutation may sensitize transformed cells to EGFR kinase inhibitors, indicating a correlation with response to therapy. Evidence Type: Predictive | Mutation: L861Q | Summary: The L861Q mutation is suggested to sensitize transformed cells to EGFR kinase inhibitors, indicating a potential response to therapy. Evidence Type: Predictive | Mutation: L790M | Summary: The L790M mutation, in combination with L858R, is described as drug-resistant, suggesting a role in therapy resistance to EGFR kinase inhibitors.

Gene→Variant (gene-first): 1956:L858R 1956:L861Q 1956:T790M

Genes: 1956

Variants: L858R L861Q T790M

[Paragraph-level] PMCID: PMC1702556 Section: RESULTS PassageIndex: 11

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: R108K | Summary: The R108K mutation in EGFR was shown to contribute to tumor development, as NIH-3T3 cells expressing this mutant produced large tumors in mice. Evidence Type: Oncogenic | Mutation: T263P | Summary: The T263P mutation in EGFR demonstrated oncogenic potential, leading to tumor formation in NIH-3T3 cells inoculated in mice. Evidence Type: Oncogenic | Mutation: A289V | Summary: The A289V mutation in EGFR was associated with tumor development, as evidenced by large tumors formed in mice expressing this mutant. Evidence Type: Oncogenic | Mutation: G598V | Summary: The G598V mutation in EGFR contributed to tumor progression, as NIH-3T3 cells expressing this variant produced significant tumors in the animal model. Evidence Type: Oncogenic | Mutation: L861Q | Summary: The L861Q mutation in EGFR was implicated in oncogenesis, resulting in tumor formation in mice injected with NIH-3T3 cells expressing this mutant.

Gene→Variant (gene-first): 1956:A289V 1956:G598V 1956:L861Q 1956:R108K 1956:T263P

Genes: 1956

Variants: A289V G598V L861Q R108K T263P

[Paragraph-level] PMCID: PMC1702556 Section: RESULTS PassageIndex: 10

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: R108K | Summary: The R108K mutation in EGFR contributes to tumor development as it allows for anchorage-independent colony formation in NIH-3T3 cells. Evidence Type: Oncogenic | Mutation: T263P | Summary: The T263P mutation in EGFR is associated with oncogenic behavior, as it enables anchorage-independent colony formation in NIH-3T3 cells. Evidence Type: Oncogenic | Mutation: A289V | Summary: The A289V mutation in EGFR demonstrates oncogenic properties by facilitating anchorage-independent colony formation in NIH-3T3 cells. Evidence Type: Oncogenic | Mutation: G598V | Summary: The G598V mutation in EGFR is implicated in oncogenic activity, as it supports anchorage-independent colony formation in NIH-3T3 cells. Evidence Type: Oncogenic | Mutation: L861Q | Summary: The L861Q mutation in EGFR is shown to have oncogenic potential, contributing to anchorage-independent colony formation in NIH-3T3 cells.

Gene→Variant (gene-first): 1956:A289V 1956:G598V 1956:L861Q 1956:R108K 1956:T263P

Genes: 1956

Variants: A289V G598V L861Q R108K T263P

[Paragraph-level] PMCID: PMC1702556 Section: RESULTS PassageIndex: 4

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: L861Q | Summary: The L861Q mutation in the EGFR kinase domain is identified as a missense mutation in glioblastoma, indicating its potential role in tumor development. Evidence Type: Oncogenic | Mutation: A289 | Summary: The A289 mutation is noted as one of the evolutionarily conserved residues affected by mutations in glioblastomas, suggesting its contribution to tumor progression. Evidence Type: Oncogenic | Mutation: R108 | Summary: The R108 mutation is also identified as an evolutionarily conserved residue affected by mutations in glioblastomas, indicating its potential role in tumor development. Evidence Type: Oncogenic | Mutation: E330K | Summary: The E330K mutation is described as germline, but it is also noted in the context of tumor samples, suggesting its involvement in oncogenic processes. Evidence Type: Oncogenic | Mutation: A289D | Summary: The A289D mutation is found in tumors without matched normal tissue, indicating its potential role in tumor development. Evidence Type: Oncogenic | Mutation: A289T | Summary: The A289T mutation is identified in tumors for which no normal tissue was available, suggesting its contribution to tumor progression. Evidence Type: Oncogenic | Mutation: R324L | Summary: The R324L mutation is noted in tumors without matched normal tissue, indicating its potential role in tumor development.

Gene→Variant (gene-first): 1956:A289 1956:A289D 1956:A289T 1956:E330K 1956:L861Q 1956:R108 1956:R324L

Genes: 1956

Variants: A289 A289D A289T E330K L861Q R108 R324L

[Paragraph-level] PMCID: PMC5019182 Section: RESULTS PassageIndex: 19

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: p.Glu542Lys | Summary: The p.Glu542Lys mutation is identified as a hotspot mutation commonly seen in cancer, indicating its contribution to tumor development or progression. Evidence Type: Oncogenic | Mutation: p.Glu545Lys | Summary: The p.Glu545Lys mutation is also noted as a hotspot mutation in cancer, suggesting its role in tumor development or progression. Evidence Type: Oncogenic | Mutation: p.His1047Arg | Summary: The p.His1047Arg mutation is described as a low-level mosaic variant, which is associated with features of CLOVES syndrome, indicating its potential contribution to tumor development or progression.

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

Genes: 5290

Variants: p.Glu542Lys p.Glu545Lys p.His1047Arg

[Paragraph-level] PMCID: PMC5019182 Section: RESULTS PassageIndex: 17

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: p.Glu453Lys | Summary: The p.Glu453Lys mutation is associated with various congenital overgrowth syndromes, indicating its role in tumor development or progression in affected tissues. Evidence Type: Oncogenic | Mutation: p.Gly914Arg | Summary: The p.Gly914Arg mutation is linked to congenital overgrowth conditions, suggesting its contribution to tumor development or progression in affected individuals.

Gene→Variant (gene-first): 5290:p.Glu453Lys 5290:p.Gly914Arg

Genes: 5290

Variants: p.Glu453Lys p.Gly914Arg

[Paragraph-level] PMCID: PMC5019182 Section: RESULTS PassageIndex: 16

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: p.Arg93Gln | Summary: The p.Arg93Gln mutation was identified in patients with features overlapping MCAP, suggesting its role in tumor development or progression, particularly as it was present in a significant percentage of alleles in peripheral blood lymphocytes. Evidence Type: Oncogenic | Mutation: p.Gly106Val | Summary: The p.Gly106Val mutation was found in a patient with congenital onset somatic overgrowth and other features, indicating its potential contribution to tumor development or progression, as it was present in a notable percentage of alleles in blood and skin. Evidence Type: Oncogenic | Mutation: p.Cys378Tyr | Summary: The p.Cys378Tyr mutation was described as a mosaic variant in a patient with hemihypertrophy and capillary malformations, suggesting its involvement in tumor development or progression, given its presence in a percentage of alleles in blood-derived DNA.

Gene→Variant (gene-first): 5290:p.Arg93Gln 5290:p.Cys378Tyr 5290:p.Gly106Val

Genes: 5290

Variants: p.Arg93Gln p.Cys378Tyr p.Gly106Val

[Paragraph-level] PMCID: PMC5019182 Section: RESULTS PassageIndex: 14

Evidence Type(s): Diagnostic, Predisposing, Oncogenic

Summary: Evidence Type: Diagnostic | Mutation: p.Glu726Lys | Summary: The p.Glu726Lys mutation is associated with classic features of MCAP, which helps in defining and classifying the disease. Evidence Type: Predisposing | Mutation: p.Glu726Lys | Summary: The presence of the p.Glu726Lys mutation in patients indicates a potential inherited risk for developing MCAP and its associated features. Evidence Type: Oncogenic | Mutation: p.Glu726Lys | Summary: The p.Glu726Lys mutation in PIK3CA is implicated in tumor development and progression, contributing to the oncogenic characteristics observed in patients with MCAP.

Gene→Variant (gene-first): 5290:p.Glu726Lys

Genes: 5290

Variants: p.Glu726Lys

[Paragraph-level] PMCID: PMC5019182 Section: RESULTS PassageIndex: 10

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: p.Asn345Thr | Summary: The p.Asn345Thr mutation is associated with a gain-of-function mechanism and contributes to tumor development. Evidence Type: Oncogenic | Mutation: p.Glu545Asp | Summary: The p.Glu545Asp mutation is associated with a gain-of-function mechanism and contributes to tumor development. Evidence Type: Oncogenic | Mutation: p.Gln546His | Summary: The p.Gln546His mutation is associated with a gain-of-function mechanism and contributes to tumor development. Evidence Type: Oncogenic | Mutation: p.Asn345Lys | Summary: The p.Asn345Lys mutation is associated with a gain-of-function mechanism and contributes to tumor development. Evidence Type: Oncogenic | Mutation: p.Glu545Lys | Summary: The p.Glu545Lys mutation is associated with a gain-of-function mechanism and contributes to tumor development. Evidence Type: Oncogenic | Mutation: p.Glu545Gly | Summary: The p.Glu545Gly mutation is associated with a gain-of-function mechanism and contributes to tumor development. Evidence Type: Oncogenic | Mutation: p.Gln546Lys | Summary: The p.Gln546Lys mutation is associated with a gain-of-function mechanism and contributes to tumor development. Evidence Type: Oncogenic | Mutation: p.Gln546Pro | Summary: The p.Gln546Pro mutation is associated with a gain-of-function mechanism and contributes to tumor development. Evidence Type: Oncogenic | Mutation: p.Tyr1021His | Summary: The p.Tyr1021His mutation is associated with a gain-of-function mechanism and contributes to tumor development. Evidence Type: Functional | Mutation: p.Ala1035Thr | Summary: The p.Ala1035Thr mutation has been demonstrated to alter molecular function through a gain-of-function mechanism. Evidence Type: Functional | Mutation: p.Ala1035Val | Summary: The p.Ala1035Val mutation has been demonstrated to alter molecular function through a gain-of-function mechanism. Evidence Type: Oncogenic | Mutation: Glu545Ala | Summary: The Glu545Ala mutation is associated with a gain-of-function mechanism and contributes to tumor development. Evidence Type: Oncogenic | Mutation: Glu545Lys | Summary: The Glu545Lys mutation is associated with a gain-of-function mechanism and contributes to tumor development.

Gene→Variant (gene-first): 5290:Glu545Ala 5290:Glu545Lys 5290:p.Ala1035Thr 5290:p.Ala1035Val 5290:p.Asn345Lys 5290:p.Asn345Thr 5290:p.Gln546His 5290:p.Gln546Lys 5290:p.Gln546Pro 5290:p.Glu545Asp 5290:p.Glu545Gly 5290:p.Glu545Lys 5290:p.Tyr1021Cys 7249:p.Tyr1021His

Genes: 5290 7249

Variants: Glu545Ala Glu545Lys p.Ala1035Thr p.Ala1035Val p.Asn345Lys p.Asn345Thr p.Gln546His p.Gln546Lys p.Gln546Pro p.Glu545Asp p.Glu545Gly p.Glu545Lys p.Tyr1021Cys p.Tyr1021His

[Paragraph-level] PMCID: PMC5019182 Section: RESULTS PassageIndex: 8

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: p.Arg93Gln | Summary: The p.Arg93Gln mutation was identified in a patient and is associated with tumor development or progression, indicating its potential role as a somatic variant contributing to cancer.

Gene→Variant (gene-first): 5290:p.Arg93Gln

Genes: 5290

Variants: p.Arg93Gln

[Paragraph-level] PMCID: PMC5019182 Section: RESULTS PassageIndex: 5

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: p.Glu545Lys | Summary: The p.Glu545Lys mutation is identified as an oncogenic mutation contributing to tumor development or progression, as indicated by its presence in the Catalogue of Somatic Mutations in Cancer (COSMIC). Evidence Type: Oncogenic | Mutation: p.His1047Arg | Summary: The p.His1047Arg mutation is also classified as an oncogenic mutation, contributing to tumor development or progression, supported by its identification in the Catalogue of Somatic Mutations in Cancer (COSMIC).

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

Genes: 5290

Variants: p.Glu545Lys p.His1047Arg

[Paragraph-level] PMCID: PMC4150988 Section: RESULTS PassageIndex: 11

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: p.M90I | Summary: The p.M90I mutation in RIT1 is associated with human primary lung adenocarcinomas and is suggested to contribute to tumor development or progression based on its presence in 'oncogene-negative' lung cancer cell lines. Evidence Type: Functional | Mutation: p.M90I | Summary: The p.M90I mutation is being studied for its role in altering the molecular function of RIT1 in the context of human cancer pathogenesis.

Gene→Variant (gene-first): 6016:p.M90I

Genes: 6016

Variants: p.M90I

[Paragraph-level] PMCID: PMC4150988 Section: RESULTS PassageIndex: 9

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: Q40L | Summary: The RIT1 Q40L mutation is associated with the activation of MEK and ERK pathways, contributing to tumor development and progression. It is part of a group of RIT1 mutations that induce phosphorylation of signaling proteins, indicating its oncogenic potential.

Gene→Variant (gene-first): 6016:Q40L

Genes: 6016

Variants: Q40L

[Paragraph-level] PMCID: PMC4150988 Section: RESULTS PassageIndex: 7

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: G12V | Summary: The KRAS G12V mutation is associated with inducing cellular transformation and tumor formation in NIH3T3 cells. Evidence Type: Oncogenic | Mutation: L858R | Summary: The EGFR L858R mutation contributes to tumor formation, as evidenced by its ability to induce significant colony formation in soft agar. Evidence Type: Oncogenic | Mutation: Q79L | Summary: The RIT1 Q79L mutation is capable of inducing cellular transformation and tumor formation in NIH3T3 cells. Evidence Type: Oncogenic | Mutation: Q40L | Summary: The RIT1 Q40L mutation shows intermediate transforming capability in the xenograft assay, indicating its potential oncogenic properties.

Gene→Variant (gene-first): 3845:G12V 1956:L858R 6016:Q40 6016:Q40L 6016:Q79L

Genes: 3845 1956 6016

Variants: G12V L858R Q40 Q40L Q79L

[Paragraph-level] PMCID: PMC4150988 Section: RESULTS PassageIndex: 6

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: F82L | Summary: The F82L mutation is associated with tumor development or progression, as it has been observed in lung adenocarcinoma and myeloid malignancies. Evidence Type: Oncogenic | Mutation: M90I | Summary: The M90I mutation contributes to tumor development or progression, being recurrently observed in lung adenocarcinoma and also found in myeloid malignancies. Evidence Type: Oncogenic | Mutation: p.M90I | Summary: The p.M90I mutation is implicated in tumor development or progression, as it has been identified in both lung adenocarcinoma and myeloid malignancies.

Gene→Variant (gene-first): 6016:F82L 6016:M90I 6016:p.M90I

Genes: 6016

Variants: F82L M90I p.M90I

[Paragraph-level] PMCID: PMC4150988 Section: RESULTS PassageIndex: 5

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: p.R122L | Summary: The p.R122L mutation is suggested to function as an oncogene in the context of RAS/RTK pathway lung adenocarcinoma, indicating its potential role in tumor development or progression.

Gene→Variant (gene-first): 6016:p.R122L

Genes: 6016

Variants: p.R122L

[Paragraph-level] PMCID: PMC4150988 Section: RESULTS PassageIndex: 4

Evidence Type(s): Oncogenic, Predisposing

Summary: Evidence Type: Oncogenic | Mutation: p.A77P | Summary: The p.A77P mutation in RIT1 is associated with tumor development as it was observed in a recurrent alteration among mutated samples. Evidence Type: Predisposing | Mutation: p.A77S | Summary: The p.A77S mutation may represent a rare germline variant, suggesting a potential inherited risk for disease, although this is unlikely based on the absence in normal genome data.

Gene→Variant (gene-first): NA:alanine 77 6016:p.A77P 6016:p.A77S

Genes: NA 6016

Variants: alanine 77 p.A77P p.A77S

[Paragraph-level] PMCID: PMC4150988 Section: RESULTS PassageIndex: 3

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: p.M90I | Summary: The p.M90I mutation in RIT1 is identified as a non-synonymous somatic mutation found in lung adenocarcinomas, suggesting its contribution to tumor development or progression.

Gene→Variant (gene-first): 6016:p.M90I

Genes: 6016

Variants: p.M90I

[Paragraph-level] PMCID: PMC3923676 Section: RESULTS PassageIndex: 16

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: E384X | Summary: The E384X mutation in ERRFI1 is described as a novel loss of function mutation that contributes to tumor development in the patient's metastatic, recurrent/refractory SIC. The evidence suggests nearly complete loss of function of ERRFI1 in the tumor, indicating its role in cancer progression. Evidence Type: Functional | Mutation: E384X | Summary: The E384X mutation results in nearly complete loss of function of the ERRFI1 protein, as indicated by the allele-specific expression data from the RNASeq analysis. This alteration in molecular function is significant in the context of the patient's tumor.

Gene→Variant (gene-first): 672:E384X

Genes: 672

Variants: E384X

[Paragraph-level] PMCID: PMC3923676 Section: RESULTS PassageIndex: 3

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: E384X | Summary: The E384X variant in ERRFI1 is described as a negative regulator of EGFR and is detected in a tumor, suggesting its contribution to tumor development or progression.

Gene→Variant (gene-first): 672:E384X

Genes: 672

Variants: E384X

[Paragraph-level] PMCID: PMC3923676 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Oncogenic, Predictive

Summary: Evidence Type: Oncogenic | Mutation: E384X | Summary: The E384X mutation in ERRFI1 is described as a somatic mutation that inactivates the gene, contributing to tumor development and progression, particularly in the context of advanced cholangiocarcinoma. Evidence Type: Predictive | Mutation: E384X | Summary: The E384X mutation is associated with a robust disease regression in a patient treated with erlotinib, indicating its potential role in predicting response to EGFR kinase inhibitors.

Gene→Variant (gene-first): 672:E384X

Genes: 672

Variants: E384X

[Paragraph-level] PMCID: PMC7081042 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: S310F | Summary: The S310F mutation in HER2 is associated with favorable outcomes and a good response to anti-HER2 therapy, indicating its predictive value for treatment efficacy. Evidence Type: Predictive | Mutation: S310Y | Summary: The S310Y mutation in HER2 is linked to favorable outcomes and a good response to anti-HER2 therapy, suggesting it may serve as a predictive biomarker for treatment. Evidence Type: Predictive | Mutation: R678Q | Summary: The R678Q mutation in HER2 appears to correlate with favorable outcomes and a good response to anti-HER2 therapy, indicating its predictive potential for treatment response. Evidence Type: Predictive | Mutation: D769H | Summary: The D769H mutation in HER2 is associated with favorable outcomes and a good response to anti-HER2 therapy, supporting its role as a predictive marker for treatment efficacy. Evidence Type: Predictive | Mutation: I767M | Summary: The I767M mutation in HER2 is linked to favorable outcomes and a good response to anti-HER2 therapy, suggesting its predictive value for treatment effectiveness. Evidence Type: Predictive | Mutation: L755S | Summary: The L755S mutation in HER2 may confer benefits when receiving neratinib or afatinib, indicating its predictive role in treatment response. Evidence Type: Predictive | Mutation: D769Y | Summary: The D769Y mutation in HER2 could confer benefits when receiving neratinib or afatinib, suggesting its predictive value for treatment outcomes. Evidence Type: Oncogenic | Mutation: L755S | Summary: The L755S mutation in HER2 is associated with resistance to trastuzumab, indicating its role in oncogenic processes related to tumor progression. Evidence Type: Oncogenic | Mutation: V842I | Summary: The V842I mutation in HER2 is linked to resistance to trastuzumab, suggesting its contribution to oncogenic behavior in tumor development. Evidence Type: Oncogenic | Mutation: K753I | Summary: The K753I mutation in HER2 is associated with resistance to trastuzumab, indicating its role in oncogenic processes related to tumor progression. Evidence Type: Oncogenic | Mutation: D769Y | Summary: The D769Y mutation in HER2 is linked to resistance to trastuzumab, suggesting its contribution to oncogenic behavior in tumor development.

Gene→Variant (gene-first): 2064:D769H 2064:D769Y 2064:I767M 1956:K753I 2064:L755S 2064:R678Q 2064:S310F 2064:S310Y 2064:V842I

Genes: 2064 1956

Variants: D769H D769Y I767M K753I L755S R678Q S310F S310Y V842I

[Paragraph-level] PMCID: PMC4159563 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Oncogenic, Diagnostic, Prognostic

Summary: Evidence Type: Oncogenic | Mutation: K27M | Summary: The K27M-H3 mutation is associated with high-grade astrocytomas and contributes to tumor development in diffuse intrinsic pontine glioma (DIPG). Evidence Type: Diagnostic | Mutation: K27M | Summary: The presence of the K27M-H3 mutation is used to classify and define the histological subtype of astrocytomas in DIPG cases. Evidence Type: Prognostic | Mutation: K27M | Summary: The K27M-H3 mutation correlates with disease behavior and outcome in pediatric brainstem gliomas, indicating that it may not predict outcomes accurately according to the current WHO grading scheme.

Gene→Variant (gene-first): 90:K27M

Genes: 90

Variants: K27M

[Paragraph-level] PMCID: PMC3366948 Section: RESULTS PassageIndex: 22

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: R1027H | Summary: The R1027H variant was present in all analyzed samples, but the data suggest that it may not represent an oncogenic event important for leukemia development in vivo. Evidence Type: Functional | Mutation: A35V | Summary: The A35V variant was present in the CCRF-CEM cell line and one additional clone, but analysis could not identify major differences in transforming properties compared to wild type TYK2. Evidence Type: Functional | Mutation: C192Y | Summary: The C192Y mutation was only found in the JURKAT line and was absent in other clones, with no significant differences in autophosphorylation observed compared to wild type TYK2.

Gene→Variant (gene-first): 4486:A35V 5395:C192Y 7297:R1027H

Genes: 4486 5395 7297

Variants: A35V C192Y R1027H

[Paragraph-level] PMCID: PMC3366948 Section: RESULTS PassageIndex: 18

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: H1297Y | Summary: The H1297Y variant in TET1 is confirmed as a somatic mutation associated with tumor development in T-ALL, as indicated by its presence in a remission sample.

Gene→Variant (gene-first): 80312:H1297Y

Genes: 80312

Variants: H1297Y

[Paragraph-level] PMCID: PMC3366948 Section: RESULTS PassageIndex: 15

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: A572T | Summary: The A572T mutation in JAK3 is described as a somatic mutation that contributes to tumor development, as it was detected in T-ALL and associated with leukemia induction in mice. Evidence Type: Oncogenic | Mutation: M511I | Summary: The M511I mutation in JAK3 is a somatic mutation that has been previously associated with AML and has been shown to transform IL3 dependent cells and induce T-ALL in mice. Evidence Type: Oncogenic | Mutation: A572V | Summary: The A572V mutation in JAK3 is noted to be a somatic variant that has been implicated in T-cell leukemia, T-cell lymphoma, and AML, contributing to tumor development by transforming hematopoietic cells and inducing leukemia in mice.

Gene→Variant (gene-first): 3718:A572 3718:A572T 3718:A572V 3718:M511I

Genes: 3718

Variants: A572 A572T A572V M511I

[Paragraph-level] PMCID: PMC8078423 Section: ABSTRACT PassageIndex: 8

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: V600E | Summary: The BRAF V600E mutation is associated with improved overall survival, objective response rate, and progression-free survival when treated with encorafenib plus cetuximab in metastatic colorectal cancer. Evidence Type: Oncogenic | Mutation: V600E | Summary: The BRAF V600E mutation contributes to tumor development and progression in metastatic colorectal cancer.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paragraph-level] PMCID: PMC8078423 Section: ABSTRACT PassageIndex: 4

Evidence Type(s): Predictive, Prognostic, Oncogenic

Summary: Evidence Type: Predictive | Mutation: V600E | Summary: The BRAF V600E mutation is associated with treatment response in patients with mCRC, as indicated by the trial comparing different treatment regimens. Evidence Type: Prognostic | Mutation: V600E | Summary: The presence of the BRAF V600E mutation correlates with overall survival (OS) outcomes in patients with mCRC, independent of the therapy received. Evidence Type: Oncogenic | Mutation: V600E | Summary: The BRAF V600E mutation is implicated in tumor development and progression in colorectal cancer.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paragraph-level] PMCID: PMC9365372 Section: RESULTS PassageIndex: 13

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: T790M | Summary: The presence of the T790M mutation correlates with the objective response rate (ORR) to abivertinib treatment, indicating its role in predicting treatment response. Evidence Type: Oncogenic | Mutation: T790M | Summary: The T790M mutation is associated with tumor development and progression, contributing to the oncogenic characteristics of the cancer.

Gene→Variant (gene-first): 1956:T790M

Genes: 1956

Variants: T790M

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

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: T790M | Summary: The T790M mutation correlates with treatment responses to abivertinib, indicating its predictive value for therapy effectiveness. Evidence Type: Oncogenic | Mutation: T790M | Summary: The T790M mutation is associated with tumor development and progression, supporting its classification as an oncogenic variant.

Gene→Variant (gene-first): 1956:T790M

Genes: 1956

Variants: T790M

[Paragraph-level] PMCID: PMC8040738 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: p.T599dup | Summary: The BRAF p.T599dup mutation is associated with the patient's response to combination targeted therapy with a selective BRAF inhibitor (dabrafenib) and MEK inhibitor (trametinib), indicating its predictive value for treatment efficacy. Evidence Type: Predictive | Mutation: p.V600E | Summary: Although the patient does not have a BRAF p.V600E mutation, the report discusses the efficacy of BRAF and MEK inhibitors in tumors harboring BRAF alterations, suggesting predictive implications for treatment strategies. Evidence Type: Oncogenic | Mutation: p.T599dup | Summary: The BRAF p.T599dup mutation contributes to tumor development or progression, as evidenced by the patient's diagnosis of a ganglioglioma and the need for targeted therapy due to tumor growth. Evidence Type: Oncogenic | Mutation: p.V600E | Summary: The BRAF p.V600E mutation is known to be oncogenic, as it is indicated for tumors that respond to targeted therapies, highlighting its role in tumor development.

Gene→Variant (gene-first): 673:V600E 673:p.T599dup 673:p.V600E

Genes: 673

Variants: V600E p.T599dup p.V600E

[Paragraph-level] PMCID: PMC2766370 Section: RESULTS PassageIndex: 8

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: c.34G>T; p.G12C | Summary: The KRAS mutation c.34G>T (p.G12C) was detected in NSCLC samples, indicating its contribution to tumor development or progression. Evidence Type: Functional | Mutation: c.34G>T; p.G12C | Summary: The mutation c.34G>T (p.G12C) alters the molecular or biochemical function of the KRAS protein, as evidenced by its detection in LCN-HRM reactions.

Gene→Variant (gene-first): 3845:c.34G>T 3845:p.G12C

Genes: 3845

Variants: c.34G>T p.G12C

[Paragraph-level] PMCID: PMC6547681 Section: ABSTRACT PassageIndex: 2

Evidence Type(s): Predictive, Functional, Oncogenic

Summary: Evidence Type: Predictive | Mutation: G101V | Summary: The BCL-2 mutation G101V is associated with reduced affinity for venetoclax, indicating that it confers drug resistance in patients with chronic lymphocytic leukaemia. Evidence Type: Functional | Mutation: G101V | Summary: Biochemical analyses reveal that the G101V mutation alters the molecular interaction of BCL-2 with venetoclax, providing insight into the structural basis for drug resistance. Evidence Type: Oncogenic | Mutation: G101V | Summary: The G101V mutation in BCL-2 contributes to tumor progression by conferring resistance to therapy, which is a characteristic of oncogenic mutations.

Gene→Variant (gene-first): 596:G101V

Genes: 596

Variants: G101V