[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: 7

Evidence Type(s): Predictive

Summary: Evidence Type: Predictive | Mutation: L858R | Summary: The L858R mutation is evaluated for its response to a diverse panel of EGFR inhibitors, indicating its potential role in predicting treatment sensitivity or resistance. Evidence Type: Predictive | Mutation: T790M | Summary: The T790M mutation is included in the evaluation of biochemical potencies against EGFR inhibitors, suggesting its relevance in predicting treatment response or resistance.

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

Genes: 1956

Variants: L858R T790M

[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: PMC11551396 Section: ABSTRACT PassageIndex: 3

Evidence Type(s): Predictive, Functional

Summary: Evidence Type: Predictive | Mutation: L858R | Summary: The L858R variant is associated with a lack of sensitivity to 1st-3rd generation EGFR tyrosine kinase inhibitors (TKIs), indicating its predictive role in therapy response. Evidence Type: Predictive | Mutation: N771insSVD | Summary: The N771insSVD variant shows a lack of sensitivity to 1st-3rd generation EGFR TKIs, suggesting its predictive role in therapy response. Evidence Type: Functional | Mutation: N771insSVD | Summary: The N771insSVD variant alters the molecular function of EGFR, as it is involved in drug sensitivity and resistance mechanisms compared to wild-type EGFR.

Gene→Variant (gene-first): 1956:L858R 1956:N771insSVD

Genes: 1956

Variants: L858R N771insSVD

[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: 3

Evidence Type(s): Predictive

Summary: Evidence Type: Predictive | Mutation: S309A | Summary: The S309A HER2 mutant reacted with trastuzumab with reduced affinity compared to wild-type HER2, indicating a correlation with therapy response. Evidence Type: Predictive | Mutation: S310F | Summary: The S310F mutant did not bind to pertuzumab but reacted with trastuzumab in a dose-dependent manner, suggesting its role in therapy response. Evidence Type: Predictive | Mutation: G309E | Summary: The G309E HER2 mutant did not bind to pertuzumab, indicating a potential resistance to this therapy. Evidence Type: Predictive | Mutation: S310Y | Summary: The S310Y HER2 mutant did not bind to pertuzumab, suggesting a potential resistance to this therapy. Evidence Type: Predictive | Mutation: G309 | Summary: The G309 HER2 mutants, including G309A and G309E, were tested for binding to pertuzumab, indicating their relevance in therapy response.

Gene→Variant (gene-first): 2064:G309 2064:G309A 2064:G309E 2064:S309A 2064:S310 2064:S310F 2064:S310Y

Genes: 2064

Variants: G309 G309A G309E S309A S310 S310F S310Y

[Paragraph-level] PMCID: PMC6843359 Section: RESULTS PassageIndex: 2

Evidence Type(s): Predictive, Functional

Summary: Evidence Type: Predictive | Mutation: S310F | Summary: The S310F mutant is not reactive to Pertuzumab, indicating a potential resistance to this therapy, while it retains binding to Trastuzumab, suggesting a correlation with treatment response. Evidence Type: Functional | Mutation: S310F | Summary: The S310F mutation alters the reactivity of the protein, affecting its binding properties with specific antibodies, which indicates a change in molecular function.

Gene→Variant (gene-first): 2064:S310F

Genes: 2064

Variants: S310F

[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: PMC10011885 Section: RESULTS PassageIndex: 20

Evidence Type(s): Predictive, Prognostic

Summary: Evidence Type: Predictive | Mutation: V600E | Summary: The BRAF V600E mutation is assessed as a predictor of progression-free survival (PFS) and overall survival (OS) based on the week 2 and week 4 baseline ratios of ctDNA levels, indicating its correlation with treatment response. Evidence Type: Prognostic | Mutation: V600E | Summary: The BRAF V600E mutation correlates with disease outcomes, as patients with higher week 2 and week 4 baseline ratios had inferior PFS and OS, suggesting its role in predicting survival independent of therapy.

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: 15

Evidence Type(s): Diagnostic, Prognostic, Predictive

Summary: Evidence Type: Diagnostic | Mutation: V600E | Summary: The BRAF V600E mutation is used to define and classify patients based on the presence of mutant ctDNA in plasma, indicating its role in diagnosing the disease. Evidence Type: Prognostic | Mutation: V600E | Summary: Higher levels of ctDNA for the BRAF V600E mutation at baseline are associated with inferior progression-free survival (PFS) and overall survival (OS), indicating its prognostic significance. Evidence Type: Predictive | Mutation: V600E | Summary: The presence of the BRAF V600E mutation correlates with clinical benefit, as patients with lower ctDNA levels achieved better outcomes, suggesting its predictive value for treatment response.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paragraph-level] PMCID: PMC8700411 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Predictive

Summary: Evidence Type: Predictive | Mutation: D770 | Summary: The EGFR-D770 mutation is associated with sensitivity to specific 2nd generation EGFR-TKIs, such as afatinib and dacomitinib, indicating its predictive value for therapy response. Evidence Type: Predictive | Mutation: G770 | Summary: The EGFR-G770 mutation shows sensitivity to approved 2nd generation EGFR TKIs and EGFR exon 20 insertion mutant-active TKIs, suggesting its predictive role in therapy response. Evidence Type: Predictive | Mutation: Y764insFQEA | Summary: The EGFR-Y764insFQEA insertion mutation is responsive to approved EGFR TKIs, highlighting its predictive significance for treatment outcomes.

Gene→Variant (gene-first): 1956:D770 1956:G770 1956:Y764insFQEA

Genes: 1956

Variants: D770 G770 Y764insFQEA

[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: 8

Evidence Type(s): Predictive

Summary: Evidence Type: Predictive | Mutation: G770 | Summary: The G770 mutation in EGFR is speculated to correlate with response to specific therapies such as afatinib, dacomitinib, poziotinib, and mobocertinib, indicating its predictive value for treatment outcomes in patients with advanced lung cancers.

Gene→Variant (gene-first): 1956:G770

Genes: 1956

Variants: G770

[Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 7

Evidence Type(s): Predictive, Functional

Summary: Evidence Type: Predictive | Mutation: V769dupASV | Summary: The V769dupASV mutation shows altered sensitivity to dacomitinib, indicating a correlation with response to therapy. Evidence Type: Functional | Mutation: V769dupASV | Summary: The V769dupASV mutation affects the biochemical function of EGFR, as evidenced by the differential inhibition of phosphorylated EGFR in response to dacomitinib.

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

Genes: 1956

Variants: V769dupASV

[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: 5

Evidence Type(s): Predictive, Functional

Summary: Evidence Type: Predictive | Mutation: D770_N771insSVD | Summary: The D770_N771insSVD mutation is associated with sensitivity to mobocertinib and poziotinib, indicating its predictive value for response to these therapies. Evidence Type: Predictive | Mutation: V769dupASV | Summary: The V769dupASV mutation shows sensitivity to mobocertinib and poziotinib, suggesting it has predictive implications for treatment response. Evidence Type: Functional | Mutation: Y764insFQEA | Summary: The Y764insFQEA mutation is described as pan-sensitive to all EGFR TKIs tested, indicating a functional alteration in response to these therapies.

Gene→Variant (gene-first): 1956:D770_N771insSVD 1956:V769dupASV 1956:Y764insFQEA

Genes: 1956

Variants: D770_N771insSVD V769dupASV Y764insFQEA

[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: 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: 33

Evidence Type(s): Predictive, Functional

Summary: Evidence Type: Predictive | Mutation: V555M | Summary: The variant V555M is associated with the expected efficacy of the inhibitor JNJ42756493, indicating a correlation with response to therapy. Evidence Type: Functional | Mutation: V561M | Summary: The variant V561M is discussed in the context of its interactions within the ATP-binding pocket, suggesting an alteration in molecular function related to drug binding.

Gene→Variant (gene-first): 2261:V555M 2260:V561M

Genes: 2261 2260

Variants: V555M V561M

[Paragraph-level] PMCID: PMC5029699 Section: RESULTS PassageIndex: 32

Evidence Type(s): Predictive

Summary: Evidence Type: Predictive | Mutation: K650E | Summary: The K650E mutation reduces the efficacy of FGFR-specific inhibitors AZD4547 and JNJ42756493, indicating a correlation with resistance to these therapies. Evidence Type: Predictive | Mutation: N540K | Summary: The N540K mutation significantly reduces the efficacy of FGFR-specific inhibitors AZD4547 and JNJ42756493, suggesting a correlation with resistance to these therapies.

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

Genes: 2261

Variants: K650E N540K

[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: 30

Evidence Type(s): Predictive, Functional

Summary: Evidence Type: Predictive | Mutation: I538V | Summary: The I538V mutation is associated with measurements of Ki values for various FGFR3 inhibitors, indicating its potential role in influencing response to therapy. Evidence Type: Predictive | Mutation: K650E | Summary: The K650E mutation is mentioned in the context of measuring Ki values for FGFR3 inhibitors, suggesting its relevance in therapeutic response. Evidence Type: Predictive | Mutation: N540K | Summary: The N540K mutation is included in the study of Ki values for FGFR3 inhibitors, indicating its potential impact on treatment response. Evidence Type: Predictive | Mutation: N540S | Summary: The N540S mutation is part of the analysis of Ki values for FGFR3 inhibitors, suggesting its relevance in predicting therapeutic outcomes. Evidence Type: Functional | Mutation: V555M | Summary: The V555M mutation is described as a gatekeeper mutation that may alter the molecular function of FGFR3, impacting its interaction with inhibitors. Evidence Type: Functional | Mutation: R669G | Summary: The R669G mutation is noted for its potential allosteric effect, indicating a change in molecular function related to FGFR3. Evidence Type: Functional | Mutation: K650E | Summary: The K650E mutation may have an allosteric effect on FGFR3, suggesting a change in its molecular function. Evidence Type: Functional | Mutation: N540K | Summary: The N540K mutation is mentioned in the context of its location near the ATP binding pocket, indicating a potential alteration in molecular function. Evidence Type: Functional | Mutation: N540S | Summary: The N540S mutation is also located near the ATP binding pocket, suggesting it may alter the molecular function of FGFR3.

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

Genes: 2263 2261

Variants: I538V K650E 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: 13

Evidence Type(s): Functional, Predictive

Summary: Evidence Type: Functional | Mutation: D641G | Summary: The D641G mutation resulted in an increase of auto-phosphorylation and substrate phosphorylation, indicating an alteration in molecular function. Evidence Type: Functional | Mutation: D641N | Summary: The D641N mutation also resulted in an increase of auto-phosphorylation and substrate phosphorylation, indicating an alteration in molecular function. Evidence Type: Predictive | Mutation: V555M | Summary: The V555M mutation is described as an acquired resistance mutation to an FGFR inhibitor, indicating a correlation with resistance to a specific therapy. Evidence Type: Functional | Mutation: V555 | Summary: The V555 mutation is associated with an increase in kinase activity, indicating an alteration in molecular function.

Gene→Variant (gene-first): 2260:D641G 2260:D641N 2261:V555 2261:V555M

Genes: 2260 2261

Variants: D641G D641N V555 V555M

[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: 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: 9

Evidence Type(s): Functional, Predictive

Summary: Evidence Type: Functional | Mutation: p.L1363P | Summary: The mutation p.L1363P in Brca1 alters the binding interaction with PALB2, leading to defects in homologous recombination repair (HRR). Evidence Type: Predictive | Mutation: p.L1363P | Summary: The mutation p.L1363P correlates with increased sensitivity to cisplatin and PARP1 inhibition, indicating a potential predictive value for therapy response. Evidence Type: Functional | Mutation: p.L1407P | Summary: The mutation p.L1407P is analyzed in the context of its potential phenocopy of p.L1363P, suggesting it may also affect molecular interactions and functions related to BRCA1. Evidence Type: Predictive | Mutation: p.L1407P | Summary: The analysis of p.L1407P in relation to p.L1363P implies a similar sensitivity to therapies, indicating a predictive aspect for treatment response.

Gene→Variant (gene-first): 672:leucine to proline 7158:p.L1363P 672:p.L1407P

Genes: 672 7158

Variants: leucine to proline p.L1363P p.L1407P

[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: 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: 7

Evidence Type(s): Predictive, Functional

Summary: Evidence Type: Predictive | Mutation: D835H | Summary: The D835H mutation is associated with resistance to type II inhibitors, indicating a correlation with treatment response and sensitivity to specific therapies. Evidence Type: Functional | Mutation: D835H | Summary: The D835H mutation alters molecular interactions, specifically affecting hydrogen bond formation and binding mode accommodation, which impacts its biochemical function.

Gene→Variant (gene-first): 2322:D835H

Genes: 2322

Variants: D835H

[Paragraph-level] PMCID: PMC4675689 Section: RESULTS PassageIndex: 4

Evidence Type(s): Predictive, Functional

Summary: Evidence Type: Predictive | Mutation: D835 | Summary: The D835 mutation is associated with resistance to type II inhibitors, suggesting a correlation with treatment response or resistance. Evidence Type: Functional | Mutation: D835 | Summary: The D835 mutation impacts the short alpha-helix, which is coupled to the drug-binding site, indicating an alteration in molecular function.

Gene→Variant (gene-first): 2322:D835

Genes: 2322

Variants: D835

[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: 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: 9

Evidence Type(s): Predictive

Summary: Evidence Type: Predictive | Mutation: p.K656E | Summary: The p.K656E mutation is associated with the potential response to FGFR inhibitors, suggesting its relevance in therapeutic strategies for the patient's pilomyxoid astrocytoma. Evidence Type: Predictive | Mutation: p.V561M | Summary: The p.V561M mutation is associated with the potential response to FGFR inhibitors, indicating its importance in therapeutic strategies for the patient's pilomyxoid astrocytoma.

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: 18

Evidence Type(s): Predictive

Summary: Evidence Type: Predictive | Mutation: D835H | Summary: The D835H mutation is associated with resistance to Sorafenib treatment, indicating its predictive value in therapy response. Evidence Type: Predictive | Mutation: D839G | Summary: The D839G mutation is also linked to resistance to Sorafenib treatment, suggesting it has predictive implications for therapy response.

Gene→Variant (gene-first): 2322:D835H 2322:D839G

Genes: 2322

Variants: D835H D839G

[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: 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: 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: 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: 16

Evidence Type(s): Predictive, Functional

Summary: Evidence Type: Predictive | Mutation: V871I | Summary: The variant EPHB4-V871I is associated with a response to treatment with TK inhibitors, indicating its predictive value in therapy sensitivity. Evidence Type: Functional | Mutation: V871I | Summary: The variant EPHB4-V871I alters the phenotype in neuroblastoma (NB) cell lines, suggesting a functional impact on molecular or biochemical processes.

Gene→Variant (gene-first): 2050:V871I

Genes: 2050

Variants: V871I

[Paragraph-level] PMCID: PMC11253285 Section: RESULTS PassageIndex: 18

Evidence Type(s): Predictive, Functional

Summary: Evidence Type: Predictive | Mutation: S4D | Summary: The S4D mutation is associated with a response to SRA737 in combination with PARP inhibitors, indicating its potential predictive value for therapy response. Evidence Type: Functional | Mutation: S4D | Summary: The S4D mutation appears to alter the molecular response to treatment, as indicated by the higher percentage of pCHK1 positive cells in tumors treated with the combination therapy.

Gene→Variant (gene-first): 142:S4D

Genes: 142

Variants: S4D

[Paragraph-level] PMCID: PMC9441062 Section: RESULTS PassageIndex: 14

Evidence Type(s): Predictive

Summary: Evidence Type: Predictive | Mutation: T790M | Summary: The T790M mutation is associated with resistance to EGFR-TKIs, indicating its role in treatment response. Evidence Type: Predictive | Mutation: C797S/G | Summary: The C797S/G mutation is identified as a resistance mechanism to EGFR-TKIs, suggesting its relevance in therapy response. Evidence Type: Predictive | Mutation: L718V/Q | Summary: The L718V/Q mutation is noted as a potential resistance mechanism to EGFR-TKIs, highlighting its impact on treatment sensitivity.

Gene→Variant (gene-first): 1956:C797S/G 1956:L718V/Q 1956:T790M

Genes: 1956

Variants: C797S/G L718V/Q T790M

[Paragraph-level] PMCID: PMC5355930 Section: ABSTRACT PassageIndex: 6

Evidence Type(s): Predictive

Summary: Evidence Type: Predictive | Mutation: H1047R | Summary: The H1047R mutation correlates with response to everolimus, indicating its predictive value for treatment sensitivity. Evidence Type: Predictive | Mutation: E545K | Summary: The E545K mutation correlates with response to everolimus, indicating its predictive value for treatment sensitivity. Evidence Type: Predictive | Mutation: E542K | Summary: The E542K mutation correlates with response to everolimus, indicating its predictive value for treatment sensitivity.

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

Genes: 5290

Variants: E542K E545K H1047R

[Paragraph-level] PMCID: PMC5355930 Section: RESULTS PassageIndex: 9

Evidence Type(s): Prognostic, Predictive

Summary: Evidence Type: Prognostic | Mutation: E542K | Summary: The E542K mutation is associated with shorter progression-free survival (PFS) and overall survival compared to wild-type PIK3CA, indicating a potential prognostic role in disease outcome. Evidence Type: Prognostic | Mutation: E545K | Summary: The E545K mutation is associated with shorter progression-free survival (PFS) and overall survival compared to wild-type PIK3CA, indicating a potential prognostic role in disease outcome. Evidence Type: Predictive | Mutation: E542K | Summary: The E542K mutation suggests a role in resistance to hormone therapy, indicating a potential predictive value regarding treatment response. Evidence Type: Predictive | Mutation: E545K | Summary: The E545K mutation suggests a role in resistance to hormone therapy, indicating a potential predictive value regarding treatment response.

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

Genes: 5290

Variants: E542K E545K

[Paragraph-level] PMCID: PMC5355930 Section: RESULTS PassageIndex: 8

Evidence Type(s): Predictive

Summary: Evidence Type: Predictive | Mutation: H1047R | Summary: The H1047R mutation in PIK3CA correlates with prolonged median progression-free survival (PFS) in patients treated with everolimus, indicating a predictive response to this therapy. Evidence Type: Predictive | Mutation: E545K | Summary: The E545K mutation in PIK3CA is associated with prolonged median progression-free survival (PFS) in patients treated with everolimus, suggesting a predictive response to this therapy. Evidence Type: Predictive | Mutation: E542K | Summary: The E542K mutation in PIK3CA correlates with prolonged median progression-free survival (PFS) in patients treated with everolimus, indicating a predictive response to this therapy.

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

Genes: 5290

Variants: E542K E545K H1047R

[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: 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: 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: PMC7099049 Section: RESULTS PassageIndex: 9

Evidence Type(s): Prognostic, Predictive

Summary: Evidence Type: Prognostic | Mutation: None | Summary: The passage discusses the use of NRG in predicting survival outcomes in HNSCC, indicating a correlation with disease outcome independent of therapy. Evidence Type: Predictive | Mutation: None | Summary: The mention of the ROC model assessing the ability of NRG in predicting survival suggests a correlation with response to treatment, indicating predictive value.

Gene→Variant (gene-first): 2264:AUC from 0

Genes: 2264

Variants: AUC from 0

[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: PMC4385014 Section: ABSTRACT PassageIndex: 4

Evidence Type(s): Predictive

Summary: Evidence Type: Predictive | Mutation: L858R | Summary: The L858R mutation is associated with sensitivity to the anti-proliferative effect of erlotinib, indicating a predictive relationship with therapy response. Evidence Type: Predictive | Mutation: T790M | Summary: The T790M mutation, when present alongside L858R, is also evaluated for sensitivity to erlotinib, suggesting a predictive relationship with therapy response.

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

Genes: 1956

Variants: L858R T790M

[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: 9

Evidence Type(s): Predictive, Functional

Summary: Evidence Type: Predictive | Mutation: V559D | Summary: The variant KIT V559D is associated with a specific response to the inhibitor CHMFL-KIT-031, demonstrating its potential predictive value for therapy effectiveness. Evidence Type: Functional | Mutation: V559D | Summary: The KIT V559D variant alters the molecular function of the kinase, as evidenced by its impact on auto-phosphorylation and downstream signaling pathways in response to treatment.

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: 3

Evidence Type(s): Predictive

Summary: Evidence Type: Predictive | Mutation: V559D | Summary: The V559D mutation correlates with sensitivity to the KIT kinase inhibitor CHMFL-KIT-031, indicating a predictive relationship for treatment response. Evidence Type: Predictive | Mutation: L576P | Summary: The L576P mutation shows sensitivity to Imatinib, suggesting it may predict treatment response in patients with this variant. Evidence Type: Predictive | Mutation: V654A | Summary: The V654A mutation exhibits moderate sensitivity to CHMFL-KIT-031, indicating a predictive relationship for treatment response. Evidence Type: Predictive | Mutation: N822K | Summary: The N822K mutation shows similar sensitivity to Imatinib as V654A, suggesting it may predict treatment response. Evidence Type: Predictive | Mutation: D816V | Summary: The D816V mutation is resistant to both Imatinib and Sunitinib, indicating a predictive relationship for treatment resistance. Evidence Type: Predictive | Mutation: T670I | Summary: The T670I mutation is resistant to both Imatinib and Sunitinib, indicating a predictive relationship for treatment resistance.

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: 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: 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: PMC8078423 Section: ABSTRACT PassageIndex: 2

Evidence Type(s): Predictive, Prognostic

Summary: Evidence Type: Predictive | Mutation: BRAFV600E | Summary: The BRAFV600E mutation is associated with response to targeted therapies such as encorafenib and cetuximab in patients with metastatic colorectal cancer. Evidence Type: Prognostic | Mutation: BRAFV600E | Summary: The presence of the BRAFV600E mutation correlates with improved overall survival and objective response rate in patients with metastatic colorectal cancer undergoing treatment.

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

Genes: 673

Variants: BRAFV600E

[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: PMC9365372 Section: RESULTS PassageIndex: 3

Evidence Type(s): Predictive, Diagnostic

Summary: Evidence Type: Predictive | Mutation: T790M | Summary: The T790M mutation is associated with screening failure for treatment, indicating its role in predicting resistance to therapy in NSCLC patients. Evidence Type: Diagnostic | Mutation: T790M | Summary: The T790M mutation is used to classify patients as T790M-negative, which is a significant reason for exclusion from treatment in the study.

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: PMC9398166 Section: RESULTS PassageIndex: 12

Evidence Type(s): Predictive

Summary: Evidence Type: Predictive | Mutation: G1202R | Summary: The G1202R mutation is associated with a response to TPX-0131 treatment, as evidenced by the correlation of tumor growth inhibition with TPX-0131 exposure and suppression of ALK phosphorylation. Evidence Type: Predictive | Mutation: L1196M | Summary: The L1196M mutation is part of the compound mutation G1202R/L1196M, which shows a correlation with response to TPX-0131 treatment, indicating its predictive value in therapy. Evidence Type: Predictive | Mutation: L1198F | Summary: The L1198F mutation is included in the compound mutation G1202R/L1198F, which demonstrates a correlation with the efficacy of TPX-0131 treatment, supporting its predictive role in therapy.

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

Genes: 238

Variants: G1202R L1196M L1198F

[Paragraph-level] PMCID: PMC9398166 Section: RESULTS PassageIndex: 11

Evidence Type(s): Predictive

Summary: Evidence Type: Predictive | Mutation: G1202R | Summary: The G1202R mutation in the EML4-ALK fusion is associated with a response to TPX-0131 treatment, demonstrating dose-dependent tumor growth inhibition (TGI) in a CDX model. Evidence Type: Predictive | Mutation: L1198F | Summary: The L1198F mutation in the EML4-ALK fusion, when combined with G1202R, shows a complete tumor regression in response to TPX-0131 treatment in a CDX model. Evidence Type: Predictive | Mutation: L1196M | Summary: The L1196M mutation in the EML4-ALK fusion, in combination with G1202R, is linked to dose-dependent efficacy of TPX-0131 treatment, resulting in complete tumor regression in a CDX model.

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

Genes: 238

Variants: G1202R L1196M L1198F

[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: 8

Evidence Type(s): Predictive

Summary: Evidence Type: Predictive | Mutation: G1202R | Summary: The G1202R mutation is associated with a response to the TPX-0131 inhibitor, indicating its predictive value for therapy effectiveness. Evidence Type: Predictive | Mutation: G1269A | Summary: The G1269A mutation is linked to the response to TPX-0131, suggesting it may predict sensitivity to this specific therapy. Evidence Type: Predictive | Mutation: L1204V | Summary: The L1204V mutation shows a correlation with the response to TPX-0131, indicating its predictive role in therapy effectiveness.

Gene→Variant (gene-first): 238:G1202R 238:G1269A 238:L1204V

Genes: 238

Variants: G1202R G1269A L1204V

[Paragraph-level] PMCID: PMC9398166 Section: RESULTS PassageIndex: 5

Evidence Type(s): Predictive

Summary: Evidence Type: Predictive | Mutation: C1156Y | Summary: C1156Y is inhibited by TPX-0131 with an IC50 of <1 nmol/L, indicating a correlation with response to this specific therapy. Evidence Type: Predictive | Mutation: E1210K | Summary: E1210K is inhibited by TPX-0131 with an IC50 of <1 nmol/L, suggesting it correlates with response to this specific therapy. Evidence Type: Predictive | Mutation: S1206C | Summary: S1206C is inhibited by TPX-0131 with an IC50 of <1 nmol/L, indicating a correlation with response to this specific therapy. Evidence Type: Predictive | Mutation: L1198F | Summary: L1198F is inhibited by TPX-0131 with an IC50 of <1 nmol/L, suggesting it correlates with response to this specific therapy. Evidence Type: Predictive | Mutation: L1196M | Summary: L1196M is inhibited by TPX-0131 with an IC50 of <1 nmol/L, indicating a correlation with response to this specific therapy. Evidence Type: Predictive | Mutation: T1151M | Summary: T1151M is inhibited by TPX-0131 with an IC50 of 1 to 2 nmol/L, suggesting it correlates with response to this specific therapy. Evidence Type: Predictive | Mutation: F1174L | Summary: F1174L is inhibited by TPX-0131 with an IC50 of <1 nmol/L, indicating a correlation with response to this specific therapy. Evidence Type: Predictive | Mutation: F1245C | Summary: F1245C is inhibited by TPX-0131 with an IC50 of <1 nmol/L, suggesting it correlates with response to this specific therapy. Evidence Type: Predictive | Mutation: R1275Q | Summary: R1275Q is inhibited by TPX-0131 with an IC50 of <1 nmol/L, indicating a correlation with response to this specific therapy. Evidence Type: Predictive | Mutation: G1202R | Summary: G1202R is inhibited by TPX-0131 with an IC50 of <1 nmol/L, suggesting it correlates with response to this specific therapy. Evidence Type: Predictive | Mutation: G1269A | Summary: G1269A is inhibited by TPX-0131 with an IC50 of 1 to 2 nmol/L, indicating a correlation with response to this specific therapy. Evidence Type: Predictive | Mutation: F1174C | Summary: F1174C is inhibited by TPX-0131 with an IC50 of 1 to 2 nmol/L, suggesting it correlates with response to this specific therapy. Evidence Type: Predictive | Mutation: V1180L | Summary: V1180L is inhibited by TPX-0131 with an IC50 of 1 to 2 nmol/L, indicating a correlation with response to this specific therapy.

Gene→Variant (gene-first): 238:C1156Y 238:D1203N 238:E1210K 238:F1174C 238:F1174L 238:F1174S 238:F1245C 238:G1202 238:G1202R 238:G1269A 238:G1269S 238:I1171N 238:L1152P 238:L1152R 238:L1196M 238:L1198F 238:R1275Q 238:S1206C 238:S1206R 238:T1151-L1152 insT 238:T1151M 238:V1180L

Genes: 238

Variants: C1156Y D1203N E1210K F1174C F1174L F1174S F1245C G1202 G1202R G1269A G1269S I1171N L1152P L1152R L1196M L1198F R1275Q S1206C S1206R T1151-L1152 insT T1151M V1180L

[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: PMC6791388 Section: RESULTS PassageIndex: 14

Evidence Type(s): Functional, Predictive

Summary: Evidence Type: Functional | Mutation: S133; Ser133; Serine 133 | Summary: The mutation at Serine 133 is associated with altered phosphorylation of CREB, indicating a change in molecular function that may contribute to MEKi resistance in leukemic cells. Evidence Type: Predictive | Mutation: S133; Ser133; Serine 133 | Summary: The increased phosphorylation of CREB at Serine 133 is speculated to promote resistance to MEK inhibitors, suggesting a correlation with treatment response.

Gene→Variant (gene-first): 7157:S133 7157:Ser133 7157:Serine 133

Genes: 7157

Variants: S133 Ser133 Serine 133

[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

[Paragraph-level] PMCID: PMC6547681 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Predictive, Functional

Summary: Evidence Type: Predictive | Mutation: G101V | Summary: The G101V mutation is associated with acquired resistance to venetoclax therapy in patients with chronic lymphocytic leukaemia, indicating its predictive value for treatment response. Evidence Type: Functional | Mutation: G101V | Summary: The G101V mutation alters the molecular interaction of BCL-2 with venetoclax, affecting drug binding and contributing to resistance. Evidence Type: Functional | Mutation: E152 | Summary: The E152 residue is involved in the binding dynamics of venetoclax, with its interaction being affected by the G101V mutation. Evidence Type: Functional | Mutation: E152A | Summary: The E152A mutation restores venetoclax binding, indicating a functional alteration that can counteract the resistance caused by the G101V mutation. Evidence Type: Functional | Mutation: V101 | Summary: The V101 residue influences the binding of venetoclax through its interaction with the G101V mutation, highlighting its role in the functional dynamics of drug resistance.

Gene→Variant (gene-first): 596:E152 596:E152A 596:G101V 596:V101

Genes: 596

Variants: E152 E152A G101V V101

[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: PMC10183391 Section: RESULTS PassageIndex: 7

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: p.L755P | Summary: The passage suggests that the efficacy of osimertinib should be tested against the p.L755P mutation, indicating a potential correlation with treatment response. Evidence Type: Oncogenic | Mutation: p.L755P | Summary: The mention of p.L755P in the context of HER2 mutations implies that it may contribute to tumor development or progression, supporting its classification as an oncogenic variant.

Gene→Variant (gene-first): 2064:p.L755P

Genes: 2064

Variants: p.L755P

[Paragraph-level] PMCID: PMC10183391 Section: RESULTS PassageIndex: 5

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: p.L755P | Summary: The p.L755P mutation in HER2 is associated with a positive response to osimertinib treatment in a patient with stage IV NSCLC, indicating its predictive value for therapy effectiveness. Evidence Type: Oncogenic | Mutation: p.L755P | Summary: The p.L755P mutation in HER2 contributes to tumor development in the context of stage IV NSCLC, supporting its classification as an oncogenic variant.

Gene→Variant (gene-first): 2064:p.L755P

Genes: 2064

Variants: p.L755P

[Paragraph-level] PMCID: PMC10183391 Section: RESULTS PassageIndex: 4

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: p.L755P | Summary: The p.L755P mutation is associated with the response to Osimertinib, indicating its predictive value for therapy effectiveness against HER2 exon 19 aberrations. Evidence Type: Oncogenic | Mutation: p.L755P | Summary: The p.L755P mutation contributes to tumor development or progression as it is classified as a HER2 exon 19 aberration.

Gene→Variant (gene-first): 2064:p.L755P

Genes: 2064

Variants: p.L755P

[Paragraph-level] PMCID: PMC10183391 Section: RESULTS PassageIndex: 2

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: c.2262_2264delinsTCC; p.(L755P) | Summary: The ERBB2 exon 19 c.2262_2264delinsTCC; p.(L755P) mutation is associated with a response to the therapy osimertinib in a patient with stage IV NSCLC. Evidence Type: Oncogenic | Mutation: c.2262_2264delinsTCC; p.(L755P) | Summary: The ERBB2 exon 19 c.2262_2264delinsTCC; p.(L755P) mutation contributes to tumor development or progression in the context of non-small cell lung cancer (NSCLC).

Gene→Variant (gene-first): 2064:c.2262_2264delinsTCC 2064:p.(L755P)

Genes: 2064

Variants: c.2262_2264delinsTCC p.(L755P)

[Paragraph-level] PMCID: PMC7612475 Section: RESULTS PassageIndex: 19

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: K700E | Summary: The SF3B1K700E mutation is hypothesized to be therapeutically exploitable, as treatment with etoposide or olaparib significantly reduced the volume of tumours with this mutation compared to wild-type tumours. Evidence Type: Oncogenic | Mutation: K700E | Summary: The SF3B1K700E mutation contributes to tumor development, as indicated by the slower growth rate of xenografts compared to wild-type, and the presence of increased DNA damage in tumours with this mutation.

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC7612475 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Predictive, Functional, Oncogenic

Summary: Evidence Type: Predictive | Mutation: K700E | Summary: The K700E mutation in SF3B1 increases cellular sensitivity to ionising radiation and various chemotherapeutic agents, including PARP inhibitors, suggesting a correlation with treatment response. Evidence Type: Functional | Mutation: K700E | Summary: The K700E mutation alters molecular function by compromising homologous recombination efficiency and inducing unscheduled R-loop formation, replication fork stalling, and defective replication fork restart. Evidence Type: Oncogenic | Mutation: K700E | Summary: The K700E mutation contributes to tumor development by inducing a BRCA-like cellular phenotype that confers synthetic lethality to DNA damaging agents and PARP inhibitors.

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC5613053 Section: ABSTRACT PassageIndex: 2

Evidence Type(s): Predictive, Prognostic

Summary: Evidence Type: Predictive | Mutation: D835Y | Summary: The D835Y mutation in FLT3 is associated with response to the FLT3/AXL inhibitor gilteritinib, indicating its predictive value for treatment efficacy in AML. Evidence Type: Predictive | Mutation: F691 | Summary: The F691 mutation in FLT3 is also associated with response to gilteritinib, suggesting its predictive role in treatment outcomes for AML. Evidence Type: Prognostic | Mutation: D835Y | Summary: The D835Y mutation in FLT3 is linked to poor overall survival in patients with AML, indicating its prognostic significance independent of therapy. Evidence Type: Prognostic | Mutation: F691 | Summary: The F691 mutation in FLT3 is associated with poor overall survival in AML, highlighting its prognostic implications.

Gene→Variant (gene-first): 2322:D835Y 2322:F691

Genes: 2322

Variants: D835Y F691

[Paragraph-level] PMCID: PMC3973211 Section: RESULTS PassageIndex: 12

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: R248W | Summary: The R248W mutation is associated with increased viability in response to etoposide treatment, suggesting a correlation with resistance to chemotherapy. Evidence Type: Predictive | Mutation: R282W | Summary: The R282W mutation is linked to higher viability after etoposide treatment, indicating a potential role in chemotherapy resistance. Evidence Type: Oncogenic | Mutation: R175H | Summary: The R175H mutation is part of p53 GOF mutations that contribute to tumor development and progression, as indicated by its association with chemoresistance. Evidence Type: Oncogenic | Mutation: R248W | Summary: The R248W mutation is implicated in tumor development and progression through its association with p53 mortality mutations and chemoresistance. Evidence Type: Oncogenic | Mutation: R273H | Summary: The R273H mutation is associated with p53 mortality mutations that contribute to tumor development and progression. Evidence Type: Oncogenic | Mutation: R282W | Summary: The R282W mutation is part of p53 mortality mutations that are linked to tumor development and progression, contributing to chemoresistance.

Gene→Variant (gene-first): 7157:R175H 7157:R248W 7157:R273H 7157:R282W

Genes: 7157

Variants: R175H R248W R273H R282W

[Paragraph-level] PMCID: PMC3973211 Section: RESULTS PassageIndex: 7

Evidence Type(s): Predictive

Summary: Evidence Type: Predictive | Mutation: R282 | Summary: The R282 mutation is associated with drug metabolism enzymes, suggesting a correlation with response or sensitivity to specific therapies.

Gene→Variant (gene-first): 7157:R282

Genes: 7157

Variants: R282

[Paragraph-level] PMCID: PMC7293710 Section: RESULTS PassageIndex: 7

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: G12V | Summary: The KRASG12V mutation is associated with increased sensitivity to the antiproliferation therapy of metformin in colorectal cancer cell lines, indicating a predictive relationship with treatment response. Evidence Type: Oncogenic | Mutation: G12V | Summary: The KRASG12V mutation contributes to tumor development and progression, as it is involved in the context of cancer cell viability and response to therapy.

Gene→Variant (gene-first): 3845:G12V

Genes: 3845

Variants: G12V

[Paragraph-level] PMCID: PMC6368247 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Oncogenic, Predictive

Summary: Evidence Type: Oncogenic | Mutation: Y537S | Summary: The Y537S mutation in ESR1 is associated with the emergence of new driver mutations during treatment, indicating its role in tumor development and progression in breast cancer. Evidence Type: Predictive | Mutation: Y537S | Summary: The presence of the Y537S mutation may correlate with resistance to CDK4/6 inhibitors, suggesting its potential impact on treatment response in patients with advanced estrogen receptor positive breast cancer.

Gene→Variant (gene-first): 5728:Y537S

Genes: 5728

Variants: Y537S

[Paragraph-level] PMCID: PMC5122709 Section: RESULTS PassageIndex: 3

Evidence Type(s): Predictive, Diagnostic, Oncogenic

Summary: Evidence Type: Predictive | Mutation: V600E | Summary: The BRAF V600E mutation is associated with treatment response to BRAF inhibitors, indicating its predictive value for therapy outcomes in melanoma patients. Evidence Type: Diagnostic | Mutation: V600E | Summary: The presence of the BRAF V600E mutation is used to confirm the diagnosis of melanoma, serving as a diagnostic marker for the disease. Evidence Type: Oncogenic | Mutation: V600E | Summary: The BRAF V600E mutation is known to contribute to tumor development and progression in melanoma, classifying it as an oncogenic variant.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paragraph-level] PMCID: PMC9900321 Section: ABSTRACT PassageIndex: 3

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: Gly-to-Asp | Summary: The Gly-to-Asp mutation (KRASG12D) is associated with the efficacy of the small-molecule KRASG12D inhibitor, MRTX1133, indicating a correlation with treatment response in pancreatic ductal adenocarcinoma models. Evidence Type: Oncogenic | Mutation: Gly-to-Asp | Summary: The Gly-to-Asp mutation (KRASG12D) is prevalent in pancreatic ductal adenocarcinoma and contributes to tumor development and progression, as evidenced by its high occurrence in patients with this cancer type.

Gene→Variant (gene-first): 3845:Gly-to-Asp

Genes: 3845

Variants: Gly-to-Asp

[Paragraph-level] PMCID: PMC6280667 Section: RESULTS PassageIndex: 9

Evidence Type(s): Predictive

Summary: Evidence Type: Predictive | Mutation: TP53 | Summary: TP53 mutations were shown to cause a broad pattern of drug resistance, with some drugs trending more sensitive to TP53 mutant cases, indicating a correlation with treatment response. Evidence Type: Predictive | Mutation: ASXL1 | Summary: ASXL1 mutations were associated with drug resistance, but also showed sensitivity to specific drugs, suggesting a predictive role in treatment response. Evidence Type: Predictive | Mutation: NRAS | Summary: NRAS mutations correlated largely with resistance to most drugs, but also showed predicted sensitivity to MAPK inhibitors, indicating a potential predictive value for therapy. Evidence Type: Predictive | Mutation: KRAS | Summary: KRAS mutations were associated with resistance to most drugs, while also showing sensitivity to MAPK inhibitors, suggesting a predictive role in treatment response. Evidence Type: Predictive | Mutation: IDH2 | Summary: IDH2 mutations conferred sensitivity to a broad spectrum of drugs, indicating a predictive association with treatment response. Evidence Type: Predictive | Mutation: IDH1 | Summary: IDH1 mutations were associated with resistance to most drugs, suggesting a predictive role in treatment response. Evidence Type: Predictive | Mutation: RUNX1 | Summary: RUNX1 mutations correlated with sensitivity to PIK3C/MTOR inhibitors, indicating a predictive association with treatment response. Evidence Type: Predictive | Mutation: FLT3 | Summary: FLT3 mutations exhibited a significant pattern of co-occurrence with sensitivity to the FDA approved drug, ibrutinib, indicating a predictive role in treatment response. Evidence Type: Predictive | Mutation: NPM1 | Summary: NPM1 mutations were significantly more sensitive to ibrutinib compared to wild type, suggesting a predictive association with treatment response. Evidence Type: Predictive | Mutation: BCOR | Summary: BCOR mutations showed sensitivity to alternative drugs, indicating a predictive role in treatment response, particularly in specific combinatorial mutation settings.

Gene→Variant (gene-first): 8233:serine/arginine

Genes: 8233

Variants: serine/arginine

[Paragraph-level] PMCID: PMC8307492 Section: ABSTRACT PassageIndex: 4

Evidence Type(s): Predictive, Prognostic

Summary: Evidence Type: Predictive | Mutation: L858R | Summary: The L858R mutation is associated with response to first-line EGFR inhibitors, with survival outcomes indicating it may not perform as well as exon 19 deletions in terms of overall survival (OS). Evidence Type: Prognostic | Mutation: L858R | Summary: The L858R mutation correlates with overall survival outcomes in non-small-cell lung cancer (NSCLC) patients, independent of therapy, suggesting its relevance in disease prognosis.

Gene→Variant (gene-first): 1956:L858R

Genes: 1956

Variants: L858R

[Paragraph-level] PMCID: PMC10690049 Section: RESULTS PassageIndex: 7

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: G12D | Summary: The KRASG12D mutation was tested in the context of a drug combination, indicating a potential correlation with resistance to therapy, as the KRASG12D MEFs were refractory to growth inhibition. Evidence Type: Oncogenic | Mutation: G12D | Summary: The KRASG12D mutation is associated with tumor development or progression, as it is mentioned in the context of MEFs that are used to study cancer behavior.

Gene→Variant (gene-first): 3845:G12D

Genes: 3845

Variants: G12D

[Paragraph-level] PMCID: PMC10690049 Section: RESULTS PassageIndex: 6

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: G12C | Summary: The KRAS G12C mutation is associated with sensitivity to specific therapies, as demonstrated by the synergistic inhibition of cell proliferation in KRAS G12C-mutant cell lines when treated with MRTX849/AMG510 and KPT9274. Evidence Type: Oncogenic | Mutation: G12C | Summary: The KRAS G12C mutation contributes to tumor development and progression, as indicated by its presence in various cancer cell lines and the observed effects of targeted therapies.

Gene→Variant (gene-first): 3845:G12C

Genes: 3845

Variants: G12C

[Paper-level Aggregated] PMCID: PMC1240052

Evidence Type(s): Predictive

Summary: Mutation: G719S | Summary: The G719S mutation is associated with resistance to gefitinib, indicating its predictive value for therapy response in lung adenocarcinoma patients.

Evidence Type: Predictive Mutation: L747_E749del A750P | Summary: The L747_E749del A750P mutation correlates with sensitivity to gefitinib and erlotinib, supporting its predictive role in therapy response for lung adenocarcinoma.

Evidence Type: Predictive Mutation: L858R | Summary: The L858R mutation is linked to increased sensitivity to gefitinib and erlotinib, demonstrating its predictive significance for treatment outcomes in lung adenocarcinoma patients. Additionally, it is associated with a response to the irreversible EGFR inhibitor CL-387,785, which shows greater effectiveness compared to gefitinib or erlotinib in inhibiting colony formation and autophosphorylation.

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

Genes: EGFR(1956)

Variants: G719S L747_E749del A750P L858R

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

Evidence Type(s): Predictive, Diagnostic

Justification: Predictive: The mention of BRAF V600E mutations in the context of optimizing patient selection for anti-EGFR monoclonal antibodies indicates a correlation with treatment response. Diagnostic: The assessment of BRAF V600E mutations suggests its role in defining or classifying patients for treatment, indicating its use as a biomarker in the context of disease.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

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

Evidence Type(s): Predictive, Diagnostic

Justification: Predictive: The passage discusses the role of the BRAF V600E mutation in predicting resistance to cetuximab plus irinotecan, indicating a correlation with treatment response. Diagnostic: The mention of BRAF V600E mutations in the context of a specific cohort of KRAS wild-type patients suggests its use in classifying or defining a subset of patients for treatment.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

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

Evidence Type(s): Predictive, Diagnostic

Justification: Predictive: The BRAF V600E mutation is mentioned in the context of predicting resistance to anti-EGFR monoclonal antibodies in metastatic colorectal cancer. Diagnostic: The BRAF V600E mutation is associated with resistance, indicating its role in defining or classifying a specific disease context (metastatic colorectal cancer).

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

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

Evidence Type(s): Predictive, Diagnostic, Oncogenic

Justification: Predictive: The passage discusses the response to bortezomib in patients with KRAS G12D-mutant lung adenocarcinomas, indicating a correlation between the variant and treatment response. Diagnostic: The KRAS G12D mutation is identified through molecular profiling as part of the patient's diagnosis, linking the variant to the classification of the disease. Oncogenic: The KRAS G12D mutation is described in the context of tumor development and progression, as it is a known driver mutation in lung adenocarcinomas.

Gene→Variant (gene-first): 3845:G12D

Genes: 3845

Variants: G12D

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

Evidence Type(s): Predictive, Diagnostic, Oncogenic

Justification: Predictive: The passage discusses the response of patients with KRAS G12D-mutant lung cancers to bortezomib, indicating a correlation between the variant and treatment response. Diagnostic: The mention of KRAS G12D in the context of lung cancers suggests its role in classifying or defining a specific subtype of the disease. Oncogenic: The variant KRAS G12D is implicated in lung cancers, indicating its contribution to tumor development or progression.

Gene→Variant (gene-first): 3845:G12D

Genes: 3845

Variants: G12D

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

Evidence Type(s): Predictive, Diagnostic, Oncogenic

Justification: Predictive: The passage discusses patients with KRAS G12D-mutant lung cancers treated with bortezomib, indicating a correlation between the variant and response to therapy. Diagnostic: The mention of "KRAS G12D-mutant lung cancers" suggests that the variant is used to classify or define a specific subtype of lung cancer. Oncogenic: The variant KRAS G12D is implicated in the context of lung adenocarcinoma, indicating its role in tumor development or progression.

Gene→Variant (gene-first): 3845:G12D

Genes: 3845

Variants: G12D

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

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The variant G292R in HER2 is associated with a complete response to pyrotinib treatment in a patient with metastatic cervical adenocarcinoma, indicating its correlation with therapy response. Oncogenic: The passage discusses the HER2 G292R variant in the context of a metastatic cervical adenocarcinoma, suggesting that it contributes to tumor development or progression.

Gene→Variant (gene-first): 2064:G292R

Genes: 2064

Variants: G292R

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

Evidence Type(s): Oncogenic, Predictive, Diagnostic

Justification: Oncogenic: The passage describes how the A66dup variant contributes to tumor development by transforming the growth of primary myeloid progenitors and Ba/F3 cells, indicating its role in oncogenesis. Predictive: The passage mentions that K-Ras proteins with the A66dup variant are hypersensitive to MEK inhibition, suggesting a correlation with response to a specific therapy. Diagnostic: The discovery of the A66dup variant in a child with an atypical myeloproliferative neoplasm suggests its potential use in defining or classifying this disease.

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

Genes: 5295

Variants: A66dup

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

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the anti-tumor efficacy of EZH2 inhibitors and their effects on tumor growth inhibition in Ezh2Y641F/+ tumors, indicating a correlation with treatment response. Oncogenic: The variant Ezh2Y641F is implicated in tumor development, as it is studied in the context of autochthonous tumors in mice, suggesting its role in contributing to tumor progression.

Gene→Variant (gene-first): 2146:Y641F

Genes: 2146

Variants: Y641F

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

Evidence Type(s): Predictive, Functional

Justification: Predictive: The passage discusses the response of melanoma cell lines with the Y641F variant to various EZH2 inhibitors, indicating a correlation between the variant and sensitivity to treatment. Functional: The passage describes how the Y641F variant affects the potency of the JQEZ5 inhibitor, demonstrating that the variant alters the molecular function of EZH2 in the context of drug response.

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

Genes: 2146

Variants: Y641F Y646F

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

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses how the PIK3CA mutation, including E545K, induces resistance to chemotherapy, indicating a correlation with treatment response. Oncogenic: The variant E545K is implicated in tumor development and progression, as evidenced by the experimental results showing increased tumor volume in the presence of this mutation.

Gene→Variant (gene-first): 5290:E545K

Genes: 5290

Variants: E545K

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

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses how the PIK3CA E545K mutation affects the sensitivity of TNBC cells to chemotherapy, specifically noting that cells with this mutation became less sensitive to the chemotherapeutic agent epirubicin. Oncogenic: The passage indicates that the PIK3CA E545K mutation promotes growth and inhibits apoptosis in TNBC cell lines, suggesting its role in tumor development and progression.

Gene→Variant (gene-first): 5290:E545K

Genes: 5290

Variants: E545K

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

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the overall response rate (ORR) of patients with specific ROS1 mutations, including G2032R, in relation to treatment with taletrectinib, indicating a correlation with treatment response. Oncogenic: The presence of ROS1 resistance mutations, including G2032R, L2026M, S1986F, and G2101A, suggests that these somatic variants contribute to tumor development or progression, particularly in the context of resistance to crizotinib.

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

Genes: 6098 4914 7294

Variants: G2032R G2101A L2026M S1986F

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

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the sensitivity of the JAK1S703I mutant PDX model to the treatment of a JAK1/2 inhibitor, ruxolitinib, indicating a correlation with response to therapy. Oncogenic: The JAK1S703I mutation is described as activating the JAK-STAT signaling pathway and driving cell proliferation, which suggests its contribution to tumor development or progression.

Gene→Variant (gene-first): 3716:S703I

Genes: 3716

Variants: S703I

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

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the patient's excellent response to dual therapy with dabrafenib and trametinib, indicating that the BRAF V600E mutation correlates with treatment response. Oncogenic: The BRAF V600E variant is described in the context of a poorly differentiated intrahepatic cholangiocarcinoma, suggesting its role in tumor development or progression.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

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

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the response rate and disease control rate of patients treated with osimertinib and selpercatinib, indicating that the variants mentioned (C797S, G12S, G810S, V600E) are associated with treatment response and resistance mechanisms. Oncogenic: The variants C797S, G12S, G810S, and V600E are described in the context of resistance mechanisms, suggesting their role in tumor development or progression in the setting of lung cancers.

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

Genes: 1956 3845 5979 673

Variants: C797S G12S G810S T790M V600E

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

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses resistance mechanisms related to specific variants, indicating their correlation with treatment response, particularly in the context of on-target and off-target resistance. Oncogenic: The variants mentioned are associated with resistance mechanisms that contribute to tumor development or progression, as they are involved in co-occurring resistance mechanisms in cancer cases.

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

Genes: 1956 3845 5979 673

Variants: C797S G12S G810S V600E V804E V804M

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

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses resistance mutations that affect the engagement of therapeutic EGFR or RET kinases, indicating a correlation with resistance to specific therapies. Oncogenic: The variants mentioned (C797S, T790M, V804M/E, G810S) are described as resistance mutations that contribute to tumor progression by impacting kinase engagement, suggesting their role in oncogenesis.

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

Genes: 1956 5979

Variants: C797S G810S T790M V804M/E

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

Evidence Type(s): Predictive, Diagnostic

Justification: Predictive: The passage discusses the presence of the EGFR T790M mutation in patients who had received prior EGFR-directed therapy, indicating a correlation with treatment response or resistance to osimertinib. Diagnostic: The mention of the EGFR T790M mutation being detectable at the time of study enrollment suggests its role in classifying or confirming the disease status in patients undergoing treatment.

Gene→Variant (gene-first): 1956:T790M

Genes: 1956

Variants: T790M

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

Evidence Type(s): Diagnostic, Predictive

Justification: Diagnostic: The passage mentions the detection of single nucleotide polymorphisms (SNPs) and their association with specific exons, indicating their role in defining or classifying genetic variants. Predictive: The passage explicitly states that there was "no correlation between these alleles and gefitinib response," which implies that the variants were evaluated for their predictive value regarding treatment response.

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

Genes: 7294 NA

Variants: G/A rs10251977 rs17290643

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

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the correlation of the L858R mutation with gefitinib response, indicating that it is associated with treatment sensitivity or resistance. Oncogenic: The L858R mutation is described as a somatic mutation found in tumor samples, suggesting its role in tumor development or progression.

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

Genes: 1956

Variants: L858R T790M

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

Evidence Type(s): Predictive, Diagnostic

Justification: Predictive: The passage indicates that the variant T790M is associated with favorable clinical efficacy of the therapy Abivertinib in patients, suggesting a correlation with treatment response. Diagnostic: The mention of patients with EGFR T790M+ NSCLC implies that the T790M variant is used to classify or define a specific subtype of non-small cell lung cancer.

Gene→Variant (gene-first): 1956:T790M

Genes: 1956

Variants: T790M

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

Evidence Type(s): Predictive, Diagnostic

Justification: Predictive: The passage discusses the evaluation of safety and efficacy of abivertinib in patients with the T790M mutation, indicating a correlation with treatment response in the context of non-small cell lung cancer. Diagnostic: The mention of the Thr790Met point mutation (T790M) being positive in patients with non-small cell lung cancer suggests its role in defining or classifying the disease subtype.

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

Genes: 1956

Variants: T790M Thr790Met

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

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

Justification: Predictive: The passage discusses the assignment of patients with EGFR-mutated NSCLC to receive osimertinib, indicating a correlation between the L858R variant and response to this specific therapy. Diagnostic: The mention of patients with EGFR-mutated NSCLC, specifically referencing the L858R variant, suggests its role in defining or classifying the disease subtype. Prognostic: The passage refers to disease-free survival (DFS) and overall survival as endpoints, indicating that the L858R variant may correlate with disease outcomes independent of therapy. Oncogenic: The context of the L858R variant being part of EGFR mutations in NSCLC implies its contribution to tumor development or progression, characteristic of oncogenic variants.

Gene→Variant (gene-first): 1956:L858R

Genes: 1956

Variants: L858R

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

Evidence Type(s): Predictive, Diagnostic

Justification: Predictive: The passage discusses the correlation between the BRAF V600E mutation and the response to treatment, indicating that all patients with confirmed responses had BRAF V600E-mutant disease, which suggests a predictive relationship with therapy response. Diagnostic: The mention of "centrally confirmed BRAF V600E-mutant disease" indicates that the variant is used to classify or confirm a specific disease subtype, supporting its role as a diagnostic marker.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

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

Evidence Type(s): Oncogenic, Predictive, Prognostic

Justification: Oncogenic: The variant V871I in the EPHB4 gene is described as contributing to increased proliferation, migration, and invasion properties in neuroblastoma cell lines, indicating its role in tumor development and progression. Predictive: The passage discusses the use of EPHB4 inhibitors that can rescue the phenotype driven by the variant V871I, suggesting a correlation with response to specific therapies. Prognostic: The passage mentions that higher EPHB4 expression is correlated with stage 4 neuroblastoma and poor overall survival, indicating a relationship between the variant and disease outcome.

Gene→Variant (gene-first): 2050:V871I

Genes: 2050

Variants: V871I

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

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses how the presence of the BRAF(V600E) variant correlates with the clinical activity of RAF inhibitors in melanoma patients, indicating a relationship between the variant and treatment response. Oncogenic: The BRAF(V600E) variant is described as contributing to tumor development and progression, particularly in the context of its role in ERK signaling and the development of resistance mechanisms in melanoma.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

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

Evidence Type(s): Predictive, Oncogenic, Functional

Justification: Predictive: The passage discusses how BRAFV600E/K is targeted for therapy with the specific inhibitor PLX4032, indicating a correlation with treatment response. Oncogenic: BRAFV600E/K is described as a mutationally active tumor-specific kinase in melanomas, suggesting its role in tumor development or progression. Functional: The passage mentions that PLX4032 alters the activity of ERK1/2 in BRAFV600E/K cells, indicating a change in molecular function related to the variant.

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

Genes: 673 4893

Variants: BRAFV600E Q61L V600E/K

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

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the effects of PLX4032 on melanoma cells, indicating a difference in response between BRAFWT and BRAFV600E cells, which suggests a correlation with treatment response. Oncogenic: The mention of BRAFV600E in the context of advanced melanoma cells implies that this somatic variant contributes to tumor development or progression, as it is associated with specific cellular behaviors in the study.

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

Genes: 673

Variants: BRAFV600E

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

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the response of melanoma cells to the therapy PLX4032, indicating that the BRAFV600E variant is associated with a lack of activation of certain proteins in response to treatment, which suggests a predictive relationship regarding therapy response. Oncogenic: The mention of BRAFV600E in the context of melanoma cells implies its role as a somatic variant contributing to tumor development or progression, as it is a well-known oncogenic mutation in melanoma.

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

Genes: 673

Variants: BRAFV600E

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

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the response of BRAFV600E cells to PLX4032, indicating a correlation with treatment response. Oncogenic: The mention of BRAFV600E in the context of downregulation of FOS and the activation of ERK1/2 suggests that this somatic variant contributes to tumor behavior and progression.

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

Genes: 673

Variants: BRAFV600E

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

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the cellular responses to PLX4032 therapy and mentions the activation of downstream ERK targets in relation to the BRAFV600E variant, indicating a correlation with treatment response. Oncogenic: The BRAFV600E variant is implicated in the inhibition of p90RSK activation in melanoma cells, suggesting its role in tumor development or progression.

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

Genes: 673

Variants: BRAFV600E

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

Evidence Type(s): Functional, Predictive

Justification: Functional: The passage discusses the enzymatic activity of BRAF variants (BRAFV600E and BRAFV600K) and how their activity is altered by treatment with PLX4032, indicating a change in molecular function. Predictive: The mention of treatment with PLX4032 and its effect on the activity of BRAF variants suggests a correlation with response to therapy, indicating predictive evidence.

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

Genes: 673

Variants: BRAFV600E BRAFV600K

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

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the response of melanoma cells with the BRAFV600E variant to the drug PLX4032, indicating a correlation with treatment sensitivity. Oncogenic: The BRAFV600E variant is implicated in the context of melanoma cells, suggesting its role in tumor development or progression.

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

Genes: 673

Variants: BRAFV600E

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

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the effects of PLX4032 on BRAFV600E/K melanoma cells, indicating a correlation between the variant and response to the therapy, specifically in terms of ERK1/2 phosphorylation. Oncogenic: The mention of BRAFV600E/K in the context of melanoma cells suggests that these somatic variants contribute to tumor development or progression, as they are associated with the activation of the RAF-MEK-ERK pathway in cancer.

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

Genes: 673

Variants: BRAFV600K V600E/K

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

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the sensitivity of BRAF mutant melanoma cell strains, including those with the V600E mutation, to the drug PLX4032, indicating a correlation between the variant and response to therapy. Oncogenic: The V600E variant is mentioned in the context of BRAF mutations in melanoma cells, suggesting its role in tumor development or progression as part of the BRAF mutation profile.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

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

Evidence Type(s): Oncogenic, Predictive

Justification: Oncogenic: The variant JAK3V674A is described as an activating allele that can transform a lymphoid pro-B-cell line, indicating its role in tumor development or progression. Predictive: The passage discusses how treatment with the compound NSC114792 inhibits JAK3 activity and decreases the viability of BaF3-JAK3V674A cells, suggesting a correlation with response to therapy.

Gene→Variant (gene-first): 3718:V674A

Genes: 3718

Variants: V674A

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

Evidence Type(s): Predictive, Functional

Justification: Predictive: The passage discusses the treatment of AML cells with BAY1436032 and its effects on DNA methylation, indicating a correlation between the IDH1R132H mutation and the response to this specific therapy. Functional: The passage describes how the IDH1R132H mutation affects DNA methylation patterns and gene expression, demonstrating an alteration in molecular function due to the variant.

Gene→Variant (gene-first): 3417:R132H

Genes: 3417

Variants: R132H