[Paragraph-level] PMCID: PMC4823091 Section: RESULTS PassageIndex: 22

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the effectiveness of HER inhibitors on colony formation in the presence of the V855A variant, indicating a correlation with response to therapy. Oncogenic: The V855A variant is mentioned in the context of colony formation assays, suggesting it contributes to tumor development or progression.

Gene→Variant (gene-first): 324:V855A

Genes: 324

Variants: V855A

[Paragraph-level] PMCID: PMC4823091 Section: RESULTS PassageIndex: 21

Evidence Type(s): Predictive, Functional

Justification: Predictive: The passage discusses the growth inhibitory effects of various inhibitors on cells expressing the HER3-V855A variant, indicating a correlation between the variant and response to specific therapies, such as afatinib and erlotinib. Functional: The variant HER3-V855A is examined in the context of its effect on cell growth and response to inhibitors, suggesting that it alters the molecular function of the HER3 receptor in relation to drug sensitivity.

Gene→Variant (gene-first): 324:V855A

Genes: 324

Variants: V855A

[Paragraph-level] PMCID: PMC4823091 Section: RESULTS PassageIndex: 7

Evidence Type(s): Predictive, Diagnostic

Justification: Predictive: The passage states that the L858R mutation sensitizes to inhibition by small molecule TKIs, indicating a correlation with response to therapy. Diagnostic: The L858R mutation is described as having the highest prevalence among activating EGFR kinase domain missense mutations, which suggests its use in defining or classifying a subtype of disease.

Gene→Variant (gene-first): 1956:L858R

Genes: 1956

Variants: L858R

[Paragraph-level] PMCID: PMC4823091 Section: RESULTS PassageIndex: 5

Evidence Type(s): Oncogenic, Predictive

Justification: Oncogenic: The HER3-V855A mutation was detected in the tumor sample, indicating that it is a somatic variant contributing to tumor development or progression. Predictive: The passage discusses the treatment of patients with advanced NSCLC with erlotinib based on the presence of an EGFR mutation, suggesting a correlation between the mutation and response to therapy.

Gene→Variant (gene-first): 2065:T-to-C 324:V855A 324:p. Val855Ala 324:valine (GTG) to alanine (GCG) at codon 855

Genes: 2065 324

Variants: T-to-C V855A p. Val855Ala valine (GTG) to alanine (GCG) at codon 855

[Paragraph-level] PMCID: PMC10183391 Section: ABSTRACT PassageIndex: 6

Evidence Type(s): Predictive, Diagnostic

Justification: Predictive: The passage discusses the activity of osimertinib in a patient with the p.L755P mutation, indicating a correlation with treatment response. Diagnostic: The variant p.L755P is described as being present in a patient with NSCLC, suggesting its role in defining or classifying the disease.

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

Genes: 2064

Variants: p.L755P

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

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the patient's response to osimertinib treatment, indicating that the variant correlates with a therapeutic response. Oncogenic: The variant is described in the context of a tumor mutation in a patient with stage IV NSCLC, suggesting its role in tumor development or progression.

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

Genes: 2064

Variants: c.2262_2264delinsTCC p.(L755P)

[Paragraph-level] PMCID: PMC10183391 Section: RESULTS PassageIndex: 7

Evidence Type(s): Predictive, Diagnostic

Justification: Predictive: The passage discusses the efficacy of osimertinib as a potential treatment for patients harboring the p.L755P mutation, indicating a correlation with response to therapy. Diagnostic: The mention of "patients harboring these mutations" suggests that the p.L755P variant is used to classify or define a specific group of patients, indicating its role in diagnosis.

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

Genes: 2064

Variants: p.L755P

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

Evidence Type(s): Predictive, Diagnostic

Justification: Predictive: The passage indicates that the p.L755P mutation is associated with an effective response to the treatment with osimertinib in a patient with stage IV NSCLC. Diagnostic: The passage mentions that the patient harbors the p.L755P mutation, which is used to classify the patient's disease subtype (HER2 exon 19 mutation in NSCLC).

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

Justification: Predictive: The passage discusses the activity of Osimertinib against the p.L755P mutation, indicating a correlation with response to therapy. Oncogenic: The mention of the p.L755P mutation in the context of HER2 exon 19 aberrations suggests that it contributes to tumor development or progression, as it is associated with a specific cancer-related mutation.

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

Genes: 2064

Variants: p.L755P

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

Evidence Type(s): Predictive, Diagnostic

Justification: Predictive: The passage discusses a patient treated with osimertinib, indicating that the variant correlates with a response to this specific therapy. Diagnostic: The variant is described as being present in a patient with stage IV NSCLC, suggesting its role in defining or classifying the disease.

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

Genes: 2064

Variants: c.2262_2264delinsTCC p.(L755P)

[Paragraph-level] PMCID: PMC6547681 Section: RESULTS PassageIndex: 12

Evidence Type(s): Functional, Predictive

Justification: Functional: The passage discusses how the G101V variant alters the binding affinity of the drug S55746, indicating a change in molecular function related to drug interaction. Predictive: The variant G101V is associated with a change in response to the drug S55746, as indicated by the differences in binding affinity and LC50 concentrations, suggesting its role in treatment sensitivity.

Gene→Variant (gene-first): 596:G101V

Genes: 596

Variants: G101V

[Paragraph-level] PMCID: PMC6547681 Section: RESULTS PassageIndex: 10

Evidence Type(s): Functional, Predictive

Justification: Functional: The passage discusses how the E152A mutation alters the binding affinity of the BCL-2 protein to venetoclax, indicating a change in molecular function related to protein binding. Predictive: The evidence suggests that the E152A mutation, when combined with G101V, restores high affinity binding to venetoclax, which implies a correlation with response to this specific therapy.

Gene→Variant (gene-first): 596:E152 596:E152A 596:G101A 596:G101V

Genes: 596

Variants: E152 E152A G101A G101V

[Paragraph-level] PMCID: PMC6547681 Section: RESULTS PassageIndex: 9

Evidence Type(s): Predictive

Justification: Predictive: The passage discusses the role of E152 in venetoclax affinity, indicating a correlation with response or sensitivity to the therapy.

Gene→Variant (gene-first): 596:E152

Genes: 596

Variants: E152

[Paragraph-level] PMCID: PMC6547681 Section: RESULTS PassageIndex: 8

Evidence Type(s): Predictive, Functional

Justification: Predictive: The passage discusses how the BCL-2 mutants, including G101V, F104L, and F104C, exhibit varying affinities for venetoclax, indicating their role in providing resistance to therapy. Functional: The passage describes how the BCL-2 mutants maintain tight binding to BH3 domains, which alters their molecular function and contributes to their ability to prevent apoptosis.

Gene→Variant (gene-first): 596:F104C 596:F104L 596:G101V

Genes: 596

Variants: F104C F104L G101V

[Paragraph-level] PMCID: PMC6547681 Section: RESULTS PassageIndex: 5

Evidence Type(s): Functional, Predictive

Justification: Functional: The passage discusses how the G101V mutation alters drug binding by changing the molecular interactions within the BCL-2 structure, indicating an alteration in biochemical function. Predictive: The evidence suggests that the G101V mutation impacts the binding affinity of venetoclax, which correlates with the response to this specific therapy.

Gene→Variant (gene-first): 596:E152 596:G101 596:G101A 596:G101V

Genes: 596

Variants: E152 G101 G101A G101V

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

Evidence Type(s): Predictive, Functional

Justification: Predictive: The variant G101V is associated with drug resistance to venetoclax in patients, indicating a correlation with treatment response. Functional: The passage discusses the biochemical analyses of the G101V mutant, revealing how it alters the affinity of venetoclax, which relates to its molecular function.

Gene→Variant (gene-first): 596:G101V

Genes: 596

Variants: G101V

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

Evidence Type(s): Predictive, Functional

Justification: Predictive: The passage discusses the emergence of the G101V mutation in patients failing therapy with venetoclax, indicating a correlation between the variant and resistance to this specific therapy. Functional: The passage describes how the G101V mutation alters the binding of venetoclax to BCL-2, indicating a change in molecular function related to drug resistance.

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

Genes: 596

Variants: E152 E152A G101V V101

[Paragraph-level] PMCID: PMC2360265 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Predictive, Diagnostic

Justification: Predictive: The passage discusses the association of classical mutations, including G719X and L858R, with sensitivity to tyrosine kinase inhibitors (TKIs) in patients with NSCLC, indicating a correlation with treatment response. Diagnostic: The mention of classical mutations in the EGFR tyrosine kinase domain being associated with sensitivity to TKIs suggests that these variants can be used to classify or define a subtype of disease in NSCLC patients.

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

Genes: 1956

Variants: G719X L858R

[Paragraph-level] PMCID: PMC8307492 Section: RESULTS PassageIndex: 18

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the T790M mutation as a mechanism of resistance to the EGFR inhibitor osimertinib, indicating its correlation with treatment response. Oncogenic: The T790M mutation is described as contributing to resistance in patients treated with EGFR inhibitors, suggesting its role in tumor progression.

Gene→Variant (gene-first): 1956:G719S 1956:L858R 1956:L861Q 1956:T790M

Genes: 1956

Variants: G719S L858R L861Q T790M

[Paragraph-level] PMCID: PMC8307492 Section: RESULTS PassageIndex: 16

Evidence Type(s): Predictive, Prognostic

Justification: Predictive: The passage discusses the proportion of patients receiving first-line targeted therapy based on the presence of the L858R mutation, indicating a correlation with treatment response. Prognostic: The median overall survival (OS) for patients with the L858R mutation is reported, demonstrating its correlation with disease outcome independent of therapy.

Gene→Variant (gene-first): 1956:L858R

Genes: 1956

Variants: L858R

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

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the association of the L858R variant with overall survival (OS) in patients treated with first-line EGFR inhibitors, indicating its relevance to treatment response. Oncogenic: The L858R variant is mentioned in the context of EGFR mutations in non-small-cell lung cancer (NSCLC), suggesting its role in tumor development or progression as part of the broader analysis of clinically actionable EGFR mutations.

Gene→Variant (gene-first): 1956:L858R

Genes: 1956

Variants: L858R

[Paragraph-level] PMCID: PMC3058384 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The B-RAFV600E mutation predicts a dependency on the MAPK signaling cascade in melanoma, and this is validated by the success of RAF and MEK inhibitors in clinical trials, indicating a correlation with treatment response. Oncogenic: The passage discusses oncogenic mutations in B-RAF, specifically the B-RAFV600E mutation, which is implicated in tumor development and progression in malignant melanomas.

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

Genes: 673

Variants: B-RAFV600E serine/threonine

[Paragraph-level] PMCID: PMC10390864 Section: RESULTS PassageIndex: 10

Evidence Type(s): Functional, Predictive

Justification: Functional: The passage discusses how the L138F variant alters HDR activity in different cell lines, indicating a change in molecular function. Predictive: The passage mentions the sensitivity of variants, including L138F, to cisplatin and olaparib, suggesting a correlation with response to these therapies.

Gene→Variant (gene-first): 5889:L138F

Genes: 5889

Variants: L138F

[Paragraph-level] PMCID: PMC10390864 Section: RESULTS PassageIndex: 9

Evidence Type(s): Predictive, Functional

Justification: Predictive: The passage discusses the sensitivity of specific RAD51C variants (G130R, K131I, T132R, Q133E, and G302V) to olaparib, indicating a correlation with response to therapy. Functional: The passage describes the introduction of RAD51C variants into a cell line and assesses their effects on homologous recombination repair (HDR), indicating that these variants alter molecular function.

Gene→Variant (gene-first): 5889:G130R 5889:G302V 5889:K131I 5889:L138F 5889:Q133E 5889:R168G 5889:T132R

Genes: 5889

Variants: G130R G302V K131I L138F Q133E R168G T132R

[Paragraph-level] PMCID: PMC10390864 Section: RESULTS PassageIndex: 7

Evidence Type(s): Functional, Predictive

Justification: Functional: The passage discusses how RAD51C missense variants alter RAD51 foci formation in response to DNA damage, indicating a change in molecular function related to DNA repair mechanisms. Predictive: The mention of "drug response findings" suggests that the variants may correlate with sensitivity or resistance to a specific therapy, indicating predictive evidence.

Gene→Variant (gene-first): 5889:A155E 5889:C135Y 5889:C147Y 5888:D108G 5889:D109Y 5889:D159Y 5889:G306R 5889:P21S 5889:V140E 5889:p.Ala155Glu 5888:p.Asp108Gly 5889:p.Asp109Tyr 5889:p.Asp159Tyr 5889:p.Cys147Tyr 5889:p.Gly306Arg 5889:p.Pro21Ser 5889:p.Val140Glu

Genes: 5889 5888

Variants: A155E C135Y C147Y D108G D109Y D159Y G306R P21S V140E p.Ala155Glu p.Asp108Gly p.Asp109Tyr p.Asp159Tyr p.Cys147Tyr p.Gly306Arg p.Pro21Ser p.Val140Glu

[Paragraph-level] PMCID: PMC10390864 Section: RESULTS PassageIndex: 5

Evidence Type(s): Predictive, Functional

Justification: Predictive: The passage discusses the influence of RAD51C missense variants on the response to cisplatin and olaparib, indicating a correlation between the variants and treatment sensitivity. Functional: The passage describes how the variants affect IC50 values in the HDR assay, suggesting that they alter molecular function related to drug response.

Gene→Variant (gene-first): 5889:E94K 5889:G306R 5889:p.Glu94Lys 5889:p.Gly306Arg

Genes: 5889

Variants: E94K G306R p.Glu94Lys p.Gly306Arg

[Paragraph-level] PMCID: PMC4868698 Section: RESULTS PassageIndex: 14

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the treatment of ruxolitinib and its effects on the phosphorylation level of STAT3 in tumors with the JAK1 S703I mutation, indicating a correlation with treatment response. Oncogenic: The mention of the JAK1 S703I mutation in the context of tumor models suggests that this somatic variant contributes to tumor development or progression.

Gene→Variant (gene-first): 3716:S703I

Genes: 3716

Variants: S703I

[Paragraph-level] PMCID: PMC4868698 Section: RESULTS PassageIndex: 11

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the sensitivity of the JAK1S703I mutation to the JAK1/2 inhibitor ruxolitinib, indicating a correlation with treatment response. Oncogenic: The passage suggests that the JAK1S703I mutation may play a critical role in tumorigenesis, indicating its contribution to tumor development.

Gene→Variant (gene-first): 3716:S703I

Genes: 3716

Variants: S703I

[Paragraph-level] PMCID: PMC4868698 Section: RESULTS PassageIndex: 10

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the anti-tumor activity of ruxolitinib in a model with the JAK1 S703I mutation, indicating a correlation with response to therapy. Oncogenic: The mention of the JAK1 S703I mutation in the context of a PDX model suggests that this somatic variant contributes to tumor development or progression.

Gene→Variant (gene-first): 3716:S703I

Genes: 3716

Variants: S703I

[Paragraph-level] PMCID: PMC7472556 Section: RESULTS PassageIndex: 23

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses how NRG1 levels increase after androgen deprivation therapy (ADT) and suggests that these elevated levels are sufficient to promote resistance to ADT, indicating a correlation with treatment response. Oncogenic: The mention of NRG1 promoting resistance to ADT implies a role in tumor development or progression, which aligns with the definition of an oncogenic variant.

Gene→Variant (gene-first): 8850:S7C

Genes: 8850

Variants: S7C

[Paragraph-level] PMCID: PMC7472556 Section: RESULTS PassageIndex: 21

Evidence Type(s): Diagnostic, Predictive

Justification: Diagnostic: The passage discusses the detection of NRG1 expression in patients with localized prostate cancer, indicating its potential role in classifying or defining the disease based on the presence or absence of NRG1 staining. Predictive: The analysis includes a comparison of NRG1 expression in patients who received neoadjuvant ADT versus those who were hormonally intact, suggesting a correlation with treatment response.

Gene→Variant (gene-first): 3084:S6 8850:S7

Genes: 3084 8850

Variants: S6 S7

[Paragraph-level] PMCID: PMC7472556 Section: RESULTS PassageIndex: 12

Evidence Type(s): Predictive, Functional

Justification: Predictive: The passage discusses resistance-promoting activity and its correlation with HER3 phosphorylation, indicating a relationship with response or resistance to therapy. Functional: The passage describes how the variant affects HER3 phosphorylation activity, suggesting an alteration in molecular function related to resistance-promoting activity.

Gene→Variant (gene-first): 5979:Q8

Genes: 5979

Variants: Q8

[Paragraph-level] PMCID: PMC5029699 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the impact of FGFR3 kinase domain variants on drug responses and highlights the distinct changes in efficacy of inhibitors based on specific activating mutations, indicating a correlation with treatment response. Oncogenic: The mention of FGFR3 variants as drivers in diverse tumors suggests that these somatic mutations contribute to tumor development or progression.

Gene→Variant (gene-first): 2261:K650E 2261:N540K 2261:R669G

Genes: 2261

Variants: K650E N540K R669G

[Paragraph-level] PMCID: PMC5029699 Section: RESULTS PassageIndex: 33

Evidence Type(s): Predictive, Functional

Justification: Predictive: The passage discusses the expected efficacy of the JNJ42756493 inhibitor towards the FGFR3 V555M variant, indicating a correlation with response to therapy based on structural interactions. Functional: The passage mentions the interactions of inhibitors within the ATP-binding pocket of the FGFR1 KD V561M variant, suggesting that the variant alters molecular function related to drug binding and efficacy.

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, Oncogenic

Justification: Predictive: The passage discusses the effect of the K650E and N540K variants on the efficacy of FGFR-specific inhibitors, indicating a correlation with treatment response. Oncogenic: The variants K650E and N540K are discussed in the context of their impact on cellular transformation and response to inhibitors, suggesting their role in tumor development or progression.

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

Justification: Predictive: The passage discusses how specific mutations, such as K650E, N540K, N540S, and V555M, affect the efficacy of various inhibitors, indicating a correlation with resistance or sensitivity to therapy. Functional: The passage describes how mutations like I538V and V555M alter the binding affinity and efficacy of inhibitors, which reflects changes in molecular function related to drug interactions.

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

Justification: Predictive: The passage discusses the Ki values of various FGFR3 variants in response to specific inhibitors, indicating a correlation between the variants and their sensitivity to therapy. Functional: The mention of mutations affecting the ATP binding pocket and potential allosteric effects suggests that these variants alter the molecular function of the FGFR3 protein.

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): Predictive, Oncogenic

Justification: Predictive: The passage discusses how mutations in protein kinases, such as V555M, can affect drug binding and implies a relationship between these mutations and drug efficacy, indicating a potential impact on treatment response. Oncogenic: The mention of V555M as an acquired mutation in FGFR3 suggests its role in tumor development or progression, particularly in the context of drug resistance.

Gene→Variant (gene-first): 2261:V555M

Genes: 2261

Variants: V555M

[Paragraph-level] PMCID: PMC5029699 Section: RESULTS PassageIndex: 13

Evidence Type(s): Predictive, Functional

Justification: Predictive: The V555M mutation is described as an acquired resistance mutation to an FGFR inhibitor, indicating a correlation with resistance to therapy. Functional: The passage discusses how the mutations, including V555M, D641G, and D641N, resulted in an increase in auto-phosphorylation and substrate phosphorylation, 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: PMC6627713 Section: RESULTS PassageIndex: 20

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

Justification: Diagnostic: The passage discusses the frequencies of MAP2K1 variants in CRC patients and their association with specific tumor characteristics, indicating their role in defining or classifying the disease. Prognostic: The variants are correlated with worse disease/progression-free survival, suggesting they have prognostic implications independent of therapy. Predictive: The passage mentions that MAP2K1 mutations are associated with de novo and acquired resistance to anti-EGFR MoAbs, indicating a predictive relationship with therapy response. Oncogenic: The variants are described as contributing to a gain of function of the MEK1 protein, which is indicative of their role in tumor development or progression.

Gene→Variant (gene-first): 5604:c.169A>G 5604:c.199G>A 5604:p.Asp67Asn 5604:p.Lys57Glu

Genes: 5604

Variants: c.169A>G c.199G>A p.Asp67Asn p.Lys57Glu

[Paragraph-level] PMCID: PMC6627713 Section: RESULTS PassageIndex: 16

Evidence Type(s): Predictive, Diagnostic

Justification: Predictive: The passage discusses the response of patients to cetuximab-based first-line therapy, specifically noting that patient P4, who carries the FBXW7 variant c.1268G>T; p.Gly423Val, had a complete response to this therapy. Diagnostic: The mention of the FBXW7 variant in the context of patient P4's treatment response suggests that it may be used to classify or define the patient's disease or treatment outcome.

Gene→Variant (gene-first): 55294:c.1268G>T 55294:p.Gly423Val

Genes: 55294

Variants: c.1268G>T p.Gly423Val

[Paragraph-level] PMCID: PMC10283448 Section: RESULTS PassageIndex: 14

Evidence Type(s): Predictive, Functional

Justification: Predictive: The passage discusses mutations identified in patients who progressed on repotrectinib treatment, suggesting a potential role of these variants in acquired resistance to the therapy. Functional: The passage indicates that further studies are necessary to investigate the functional role of the mutations, implying that these variants may alter molecular or biochemical functions related to resistance mechanisms.

Gene→Variant (gene-first): 1050:196_197insHP 7157:E171G 896:E253Q 2064:H178Q 7157:H179Y 5925:H555R 2064:R143Q

Genes: 1050 7157 896 2064 5925

Variants: 196_197insHP E171G E253Q H178Q H179Y H555R R143Q

[Paragraph-level] PMCID: PMC10283448 Section: RESULTS PassageIndex: 12

Evidence Type(s): Predictive, Diagnostic

Justification: Predictive: The passage discusses the clinical activity of repotrectinib in a patient with the G2032R mutation, indicating a response to therapy, which aligns with predictive evidence. Diagnostic: The G2032R mutation is identified in the context of a ROS1-rearranged patient, suggesting its role in defining the patient's disease subtype.

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

Genes: 6098

Variants: G2032R

[Paragraph-level] PMCID: PMC10283448 Section: RESULTS PassageIndex: 10

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the response of the ROS1-G2032R mutation to various therapies, specifically mentioning the effectiveness of cabozantinib and repotrectinib in inhibiting growth, which correlates with treatment response. Oncogenic: The ROS1-G2032R mutation is implicated in tumor growth, as indicated by the investigation of its effects in Ba/F3 cells and the context of progression on crizotinib treatment, suggesting its role in tumor development.

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

Genes: 6098

Variants: G2032R

[Paragraph-level] PMCID: PMC10283448 Section: RESULTS PassageIndex: 9

Evidence Type(s): Predictive

Justification: Predictive: The passage indicates that repotrectinib is effective against crizotinib-resistant ROS1 G2032R, suggesting a correlation between the variant and response to therapy.

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

Genes: 6098

Variants: G2032R

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

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the high prevalence of the crizotinib-resistant ROS1-G2032R mutation and its implications for treatment response, indicating a correlation with resistance to therapy. Oncogenic: The mention of the ROS1-G2032R mutation in the context of crizotinib resistance suggests that it contributes to tumor progression, which aligns with the definition of an oncogenic variant.

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

Genes: 6098

Variants: G2032R

[Paragraph-level] PMCID: PMC7568619 Section: ABSTRACT PassageIndex: 2

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The variant L1196Q is associated with the development of resistance to ALK inhibitors, and its identification guided the prescription of a newer ALK inhibitor, ceritinib, which resulted in a partial response in the patient. Oncogenic: The passage indicates that the L1196Q mutation is a secondary mutation that developed in the context of drug resistance, suggesting it contributes to tumor progression and the development of resistance to therapy.

Gene→Variant (gene-first): 238:L1196Q

Genes: 238

Variants: L1196Q

[Paragraph-level] PMCID: PMC9859631 Section: RESULTS PassageIndex: 12

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses various mutations, including Y1230H, D1288N L1195I, and L1195V, which are described as secondary mutations associated with MET TKI resistance, indicating a correlation with treatment response. Oncogenic: The mention of mutations contributing to resistance against targeted therapies suggests that these variants may play a role in tumor development or progression, particularly in the context of lung cancer.

Gene→Variant (gene-first): 79811:D1288N L1195I 79811:L1195V 79811:Y1230H 2064:c.1899-936_1946+520del

Genes: 79811 2064

Variants: D1288N L1195I L1195V Y1230H c.1899-936_1946+520del

[Paragraph-level] PMCID: PMC9859631 Section: RESULTS PassageIndex: 11

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the presence of the EGFR L858R variant in a patient with advanced LUAD and its association with resistance to osimertinib, indicating a correlation with treatment response. Oncogenic: The mention of the EGFR L858R variant and its role in the context of advanced LUAD suggests that it contributes to tumor development or progression, particularly as it is associated with resistance mechanisms.

Gene→Variant (gene-first): 2064:D769Y 2064:L755S 1956:L858R 2064:c.1899-32_1909del

Genes: 2064 1956

Variants: D769Y L755S L858R c.1899-32_1909del

[Paragraph-level] PMCID: PMC9859631 Section: RESULTS PassageIndex: 5

Evidence Type(s): Diagnostic, Predictive

Justification: Diagnostic: The passage discusses the detection of ERBB2 variants in patients, indicating their association with specific cases, which supports their use in defining or classifying a disease subtype. Predictive: The mention of the novel variant ERBB2 c.1899-2A>G being detected after treatment suggests a potential correlation with treatment response, indicating its relevance in predicting therapy outcomes.

Gene→Variant (gene-first): 2064:c.1899-2A>G 2064:c.1899-880_1946+761del

Genes: 2064

Variants: c.1899-2A>G c.1899-880_1946+761del

[Paragraph-level] PMCID: PMC4748120 Section: RESULTS PassageIndex: 15

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the sensitivity of cells expressing K-RasG12D to specific therapies, indicating a correlation between the variant and response to treatment with MEK and PI3K inhibitors. Oncogenic: The mention of K-RasG12D in the context of transformed Ba/F3 cells suggests that this somatic variant contributes to tumor development or progression, as it is involved in cytokine-independent growth.

Gene→Variant (gene-first): 3845:K-RasG12D

Genes: 3845

Variants: K-RasG12D

[Paragraph-level] PMCID: PMC5792548 Section: RESULTS PassageIndex: 14

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the effects of combination therapies on cell proliferation in osimertinib-resistant cell lines, indicating a relationship between the presence of the T790M mutation and the response to therapy, specifically mentioning osimertinib and naquotinib. Oncogenic: The T790M mutation is maintained in the osimertinib-resistant RPC-9/OsiR cells, suggesting its role in tumor development or progression, particularly in the context of resistance to therapy.

Gene→Variant (gene-first): 1956:C797S 1956:T790M

Genes: 1956

Variants: C797S T790M

[Paragraph-level] PMCID: PMC5792548 Section: RESULTS PassageIndex: 10

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses gefitinib-resistant lung adenocarcinoma cell lines harboring the EGFR exon 19del and T790M mutations, indicating a correlation with resistance to therapy, specifically gefitinib. Oncogenic: The mention of the EGFR exon 19del and T790M mutations in the context of gefitinib resistance suggests that these somatic variants contribute to tumor development or progression in lung adenocarcinoma.

Gene→Variant (gene-first): 1956:19del 1956:T790M

Genes: 1956

Variants: 19del T790M

[Paragraph-level] PMCID: PMC5792548 Section: RESULTS PassageIndex: 8

Evidence Type(s): Oncogenic, Predictive

Justification: Oncogenic: The passage discusses the role of the EGFR exon 19del variant in the development of a resistant cell line, indicating that this somatic variant contributes to tumor progression and resistance mechanisms in lung cancer cells. Predictive: The passage mentions that the combination of EGFR-TKIs and MET inhibitors showed an excellent inhibitory effect on cell proliferation in the resistant cell line, suggesting a correlation between the variant and response to therapy.

Gene→Variant (gene-first): 1956:19del

Genes: 1956

Variants: 19del

[Paragraph-level] PMCID: PMC5792548 Section: RESULTS PassageIndex: 4

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the acquired EGFR C797S mutation in the context of resistance to osimertinib, indicating that this variant correlates with resistance to a specific therapy. Oncogenic: The C797S mutation is described as contributing to resistance in cell lines, suggesting its role in tumor progression or development in the context of EGFR-TKI treatment.

Gene→Variant (gene-first): 1956:C797S

Genes: 1956

Variants: C797S

[Paragraph-level] PMCID: PMC5792548 Section: RESULTS PassageIndex: 3

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the establishment of naquotinib-resistant lung cancer cells and mentions the effectiveness of naquotinib in inhibiting cell proliferation, indicating a correlation between the variants (19del and T790M) and resistance to therapy. Oncogenic: The presence of the T790M mutation in acquired gefitinib-resistant cells suggests that it contributes to tumor development or progression, as it is associated with resistance mechanisms in lung cancer.

Gene→Variant (gene-first): 1956:19del 1956:T790M

Genes: 1956

Variants: 19del T790M

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

Evidence Type(s): Predictive, Diagnostic, Oncogenic

Justification: Predictive: The passage discusses the EGFR T790M mutation in the context of treatment response to osimeritinib and the development of resistance, indicating a correlation with therapy outcomes. Diagnostic: The passage states that the EGFR T790M mutation is used to identify patients with non-small cell lung cancer who are eligible for treatment with osimeritinib, thus classifying it as a diagnostic marker. Oncogenic: The EGFR T790M mutation is described as contributing to resistance in lung cancer, which implies its role in tumor progression and development.

Gene→Variant (gene-first): 1956:T790M

Genes: 1956

Variants: T790M

[Paragraph-level] PMCID: PMC8285406 Section: RESULTS PassageIndex: 22

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the correlation between the FGFR3 S249C variant and the response to treatment with FGFR TKIs, indicating that patients with this mutation exhibited partial or complete responses, which aligns with predictive evidence. Oncogenic: The FGFR3 S249C variant is described as the most frequent mutation of FGFR3, suggesting its role in tumor development or progression, which supports its classification as oncogenic.

Gene→Variant (gene-first): 2261:S249C

Genes: 2261

Variants: S249C

[Paragraph-level] PMCID: PMC8285406 Section: RESULTS PassageIndex: 20

Evidence Type(s): Oncogenic, Predictive

Justification: Oncogenic: The passage discusses the transforming activities of FGFR3 S249C compound mutations, indicating that these mutations contribute to tumor development or progression as demonstrated by their evaluation in 3T3 and Ba/F3 cells. Predictive: The passage mentions the sensitivity to E7090 and erdafitinib in relation to the mutations, indicating a correlation with treatment response, which aligns with predictive evidence.

Gene→Variant (gene-first): 2261:K650E 2261:K650M 2261:S249C 2261:Y373C

Genes: 2261

Variants: K650E K650M S249C Y373C

[Paragraph-level] PMCID: PMC8285406 Section: RESULTS PassageIndex: 16

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the effectiveness of E7090 and erdafitinib in treating tumors with specific variants, indicating a correlation between the variants and the response to these therapies. Oncogenic: The variants are described in the context of tumor growth and response to treatment, suggesting that they contribute to tumor development or progression.

Gene→Variant (gene-first): 2261:K650M 2261:K650N 2260:N546K 2263:N549K 2261:R248C

Genes: 2261 2260 2263

Variants: K650M K650N N546K N549K R248C

[Paragraph-level] PMCID: PMC8285406 Section: RESULTS PassageIndex: 14

Evidence Type(s): Predictive, Functional

Justification: Predictive: The passage discusses the response of FGFR3 variants K650M and K650N to FGFR TKIs, indicating their sensitivity to specific therapies, which aligns with predictive evidence. Functional: The passage describes the alteration of phosphorylation status of the FGFR3 variants K650M and K650N in response to treatment, indicating a change in molecular function due to the variants.

Gene→Variant (gene-first): 2261:K650M 2261:K650N

Genes: 2261

Variants: K650M K650N

[Paragraph-level] PMCID: PMC8285406 Section: RESULTS PassageIndex: 13

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the sensitivity and resistance of FGFR variants, including N546K and N549D/K, to FGFR inhibitors, indicating a correlation with response to therapy. Oncogenic: The passage mentions that KRAS G12V is part of a cluster composed mainly of oncogenic variants, suggesting its role in tumor development or progression.

Gene→Variant (gene-first): 3845:G12V 2260:N546K 2263:N549D/K

Genes: 3845 2260 2263

Variants: G12V N546K N549D/K

[Paragraph-level] PMCID: PMC8285406 Section: RESULTS PassageIndex: 12

Evidence Type(s): Predictive

Justification: Predictive: The passage discusses how different missense variants at specific amino acid positions in FGFR2 and FGFR3 correlate with varying drug sensitivities to FGFR inhibitors, indicating a relationship between the variants and treatment response.

Gene→Variant (gene-first): 2263:K656 2263:K656E/M 2263:N549 2263:N549D/H

Genes: 2263

Variants: K656 K656E/M N549 N549D/H

[Paragraph-level] PMCID: PMC8285406 Section: RESULTS PassageIndex: 11

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the drug sensitivity of FGFR variants in response to various targeted therapies, indicating that certain variants are sensitive or resistant to specific inhibitors, which aligns with predictive evidence. Oncogenic: The context of transformed FGFR variants suggests that these somatic mutations contribute to tumor development or progression, particularly as they are assessed for their response to targeted therapies.

Gene→Variant (gene-first): 2264:N535K 2260:N546K 2263:N549D/K 2263:V550L

Genes: 2264 2260 2263

Variants: N535K N546K N549D/K V550L

[Paragraph-level] PMCID: PMC8203843 Section: ABSTRACT PassageIndex: 4

Evidence Type(s): Predictive

Justification: Predictive: The passage indicates that IDH1 R132H is associated with sensitivity to PARP inhibitors, which correlates the variant with a specific therapy response.

Gene→Variant (gene-first): 3417:R132H

Genes: 3417

Variants: R132H

[Paragraph-level] PMCID: PMC8255005 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the resistance of FLT3 mutations, specifically F691L, to FLT3 inhibitors and highlights the efficacy of KX2-391 in overcoming this resistance, indicating a correlation with treatment response. Oncogenic: The FLT3 mutations, including D835 and F691, are described as contributing to tumor development and progression in acute myeloid leukemia (AML), which supports their classification as oncogenic variants.

Gene→Variant (gene-first): 2322:D835 2322:D835Y 2322:F691 2322:F691L

Genes: 2322

Variants: D835 D835Y F691 F691L

[Paragraph-level] PMCID: PMC10527017 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the resistance of HP breast cancers to the pan-HER tyrosine kinase inhibitor, neratinib, and the effectiveness of combining neratinib with trastuzumab deruxtecan and CDK4/6 inhibitors, indicating a correlation with treatment response. Oncogenic: The study involves genetically engineered mice with the HER2V777L mutation, showing accelerated tumor formation and increased invasion, which supports the notion that this somatic variant contributes to tumor development and progression.

Gene→Variant (gene-first): 2064:V777L

Genes: 2064

Variants: V777L

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

Evidence Type(s): Functional, Predictive

Justification: Functional: The passage discusses the phosphorylation levels of proteins in relation to the HER2V777L mutation, indicating that the variant alters molecular function, specifically in signaling pathways related to cancer. Predictive: The mention of increased phosphorylation of annexin A2 being associated with drug resistance suggests a correlation between the HER2V777L variant and resistance to therapy.

Gene→Variant (gene-first): 2064:V777L

Genes: 2064

Variants: V777L

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

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the response of the WHIM51 PDX model to the drug combination of neratinib plus T-DXd, indicating that the G776insYVMA and V777L mutations correlate with a significant tumor regression in response to this therapy. Oncogenic: The G776insYVMA and V777L mutations are associated with tumor regression in the context of breast cancer, suggesting that these somatic variants contribute to tumor development or progression as evidenced by their behavior in the experimental model.

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

Genes: 2064

Variants: G776insYVMA V777L

[Paragraph-level] PMCID: PMC4821611 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses ALK mutations (p.C1156Y and p.G1269A) in the context of crizotinib resistance, indicating a correlation between these variants and resistance to the therapy. Oncogenic: The ALK mutations are described as being detected in post-treatment tumor samples, suggesting their contribution to tumor development or progression in the context of crizotinib resistance.

Gene→Variant (gene-first): 238:p.C1156Y 238:p.G1269A

Genes: 238

Variants: p.C1156Y p.G1269A

[Paragraph-level] PMCID: PMC4821611 Section: RESULTS PassageIndex: 10

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses mutations in the ALK gene, specifically p.C1156Y and p.G1269A, which have been reported to confer resistance against crizotinib, indicating a correlation with treatment response. Oncogenic: The presence of mutations in the ALK gene, such as p.C1156Y and p.G1269A, suggests that these somatic variants contribute to tumor development or progression, as they were identified in post-treatment tumor samples.

Gene→Variant (gene-first): 238:c.3467G>A 238:c.3806G>C 238:p.C1156Y 238:p.G1269A

Genes: 238

Variants: c.3467G>A c.3806G>C p.C1156Y p.G1269A

[Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 19

Evidence Type(s): Predictive, Functional

Justification: Predictive: The passage discusses the response of cells expressing mutant FGFR3 variants (S249C, Y375C, K652E) to FGF1 stimulation, indicating a correlation with receptor activation and signaling, which relates to treatment response. Functional: The passage describes how the variants S249C, Y375C, and K652E affect the phosphorylation of FGFR3, indicating that these mutations alter the molecular function of the receptor in response to ligand stimulation.

Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y375C

Genes: 2261

Variants: K652E S249C Y375C

[Paragraph-level] PMCID: PMC5652823 Section: ABSTRACT PassageIndex: 7

Evidence Type(s): Predictive, Diagnostic

Justification: Predictive: The passage indicates that patients with the EGFR-T790M mutation responded to the 3rd-generation EGFR-TKI osimertinib, suggesting a correlation between the variant and treatment response. Diagnostic: The EGFR-T790M mutation is mentioned as being revealed in re-biopsies at progression, indicating its role in defining or confirming the presence of a specific disease state in patients treated with EGFR-TKIs.

Gene→Variant (gene-first): 1956:T790M

Genes: 1956

Variants: T790M

[Paragraph-level] PMCID: PMC5122709 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Predictive, Diagnostic

Justification: Predictive: The passage discusses the effectiveness of BRAF inhibitors in patients with metastatic melanoma harboring BRAF V600 mutations, indicating a correlation with treatment response. Diagnostic: The BRAF V600 mutation is used to define and classify patients with metastatic melanoma, as all patients in the study had BRAFV600E mutations.

Gene→Variant (gene-first): 673:V600

Genes: 673

Variants: V600

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

Evidence Type(s): Predictive, Diagnostic, Oncogenic

Justification: Predictive: The passage discusses patients treated with BRAF inhibitors, specifically mentioning the BRAF V600E mutation, which correlates with response to these therapies. Diagnostic: The passage states that all patients tested positive for the BRAF V600E mutation, indicating its use in defining or confirming the presence of a specific subtype of melanoma. Oncogenic: The BRAF V600E mutation is implicated in the development of melanoma, suggesting its role as a somatic variant contributing to tumor progression.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paragraph-level] PMCID: PMC1952070 Section: ABSTRACT PassageIndex: 6

Evidence Type(s): Predictive, Diagnostic

Justification: Predictive: The passage discusses mutations, including the L858R point mutation, in the context of their correlation with response to treatment, indicating a predictive relationship. Diagnostic: The mention of the L858R mutation as part of a group of mutations previously correlated with response suggests its role in defining or classifying a disease subtype.

Gene→Variant (gene-first): 1956:L858R

Genes: 1956

Variants: L858R

[Paragraph-level] PMCID: PMC8688876 Section: RESULTS PassageIndex: 16

Evidence Type(s): Functional, Predictive

Justification: Functional: The passage discusses how specific amino acid substitutions affect RAF affinity, indicating that these variants alter molecular function related to protein interactions. Predictive: The passage predicts changes in RAF affinity for various variants, suggesting a correlation with potential therapeutic responses or resistance based on their affinity levels.

Gene→Variant (gene-first): 3265:A146V 673:A18D 3265:A59T 3845:G12 3845:G12S 3845:G13C 3265:G13V 3845:K117N 3845:L19F 3845:Q22K 3845:Q61H 3845:Q61P 4893:Q61R 3845:R164Q 22882:T74P

Genes: 3265 673 3845 4893 22882

Variants: A146V A18D A59T G12 G12S G13C G13V K117N L19F Q22K Q61H Q61P Q61R R164Q T74P

[Paragraph-level] PMCID: PMC8688876 Section: RESULTS PassageIndex: 13

Evidence Type(s): Functional, Predictive, Oncogenic

Justification: Functional: The passage discusses how mutated KRAS proteins may alter GAP binding and change GAP-mediated hydrolysis rates, indicating that the variants affect molecular function. Predictive: The analysis provides a probability density distribution and suggests that the variants can predict relative levels for mutations based on their GAP-mediated hydrolysis rates, indicating a correlation with functional outcomes. Oncogenic: The context of the variants being associated with cancer and their effects on GAP-mediated hydrolysis suggests that these somatic variants contribute to tumor development or progression.

Gene→Variant (gene-first): 3845:A146T 3265:A146V 673:A18D 3265:A59T 3845:G12A/R 3845:G12D 3845:G12S 3845:G13C 3845:G13D 3265:G13V 3845:K117N 3845:L19F 3845:Q22K 3845:Q61H 22882:T74P

Genes: 3845 3265 673 22882

Variants: A146T A146V A18D A59T G12A/R G12D G12S G13C G13D G13V K117N L19F Q22K Q61H T74P

[Paragraph-level] PMCID: PMC7545690 Section: RESULTS PassageIndex: 15

Evidence Type(s): Prognostic, Predictive

Justification: Prognostic: The passage discusses how the rs3786362 variant correlates with progression-free survival (PFS) and overall survival (OS) in metastatic colorectal cancer (mCRC) patients, indicating its association with disease outcomes independent of therapy. Predictive: The passage suggests that TYMS rs3786362 could be a predictive biomarker for survival in mCRC patients, indicating a potential correlation with treatment response in specific subgroups.

Gene→Variant (gene-first): 7298:rs3786362

Genes: 7298

Variants: rs3786362

[Paragraph-level] PMCID: PMC7545690 Section: RESULTS PassageIndex: 13

Evidence Type(s): Predictive

Justification: Predictive: The passage discusses the correlation of the variant rs3786362 with responses to first-line chemotherapy in mCRC patients, indicating that the G allele is associated with reduced disease control rate (DCR), which relates to treatment response.

Gene→Variant (gene-first): 7298:rs3786362

Genes: 7298

Variants: rs3786362

[Paragraph-level] PMCID: PMC7545690 Section: RESULTS PassageIndex: 12

Evidence Type(s): Predictive

Justification: Predictive: The passage discusses the correlation between the variant rs3786362 and the disease control rate (DCR) in metastatic colorectal cancer (mCRC) patients, indicating a relationship with treatment response.

Gene→Variant (gene-first): 7298:rs3786362

Genes: 7298

Variants: rs3786362

[Paragraph-level] PMCID: PMC7545690 Section: RESULTS PassageIndex: 8

Evidence Type(s): Prognostic, Predictive

Justification: Prognostic: The passage discusses the correlation of SNPs, specifically rs3786362 and rs369803, with progression-free survival (PFS) in metastatic colorectal cancer (mCRC) patients, indicating their association with disease outcome. Predictive: The passage mentions the correlation of SNPs with disease control rate (DCR), suggesting that these variants may influence treatment response in mCRC patients.

Gene→Variant (gene-first): 10841:rs10432965 2346:rs369803 7298:rs3786362 113235:rs4795436

Genes: 10841 2346 7298 113235

Variants: rs10432965 rs369803 rs3786362 rs4795436

[Paragraph-level] PMCID: PMC7325368 Section: ABSTRACT PassageIndex: 6

Evidence Type(s): Predictive, Diagnostic

Justification: Predictive: The passage discusses the response of patients with B-RAFV600E mutations to therapy, indicating a correlation between the variant and treatment outcomes in various cancers. Diagnostic: The mention of B-RAFV600E in the context of specific cancer types suggests its use as a biomarker to classify or define these diseases.

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

Genes: 673

Variants: B-RAFV600E

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

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses lifirafenib as an inhibitor specifically targeting B-RAFV600E, indicating a correlation with response to therapy in patients with B-RAF-mutated tumors. Oncogenic: The mention of B-RAFV600E in the context of mutated solid tumors suggests that this somatic variant contributes to tumor development or progression.

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

Genes: 673

Variants: B-RAFV600E

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

Evidence Type(s): Predictive, Diagnostic, Oncogenic

Justification: Predictive: The passage discusses the confirmed responses and stable disease (SD) in patients with K-RAS mutations, including G13D, indicating a correlation with treatment response. Diagnostic: The mention of K-RAS mutations, including G13D, in the context of specific cancer types (endometrial cancer and NSCLC) suggests its role in classifying or defining these diseases. Oncogenic: The reference to K-RAS mutations, including G13D, contributing to tumor development in specific cancer types supports the classification of this variant as oncogenic.

Gene→Variant (gene-first): 3845:G13D

Genes: 3845

Variants: G13D

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

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the responses of patients with B-RAF mutations to therapy, indicating a correlation between the B-RAFV600E variant and treatment response, which is characteristic of predictive evidence. Oncogenic: The B-RAFV600E variant is mentioned in the context of patients with B-RAF-mutated tumors, suggesting its role in tumor development or progression, which aligns with oncogenic evidence.

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

Genes: 673

Variants: B-RAFV600E

[Paragraph-level] PMCID: PMC8887939 Section: RESULTS PassageIndex: 11

Evidence Type(s): Predictive, Diagnostic

Justification: Predictive: The passage discusses the overall response rate (ORR) and median progression-free survival (PFS) associated with the HER2 insertion mutations, indicating a correlation with treatment response. Diagnostic: The mention of the frequency of the HER2 Y772_A775dupYVMA mutation in patients suggests its role in defining or classifying a specific disease subtype.

Gene→Variant (gene-first): 2064:A775dupYVMA 2064:G776delinsVC

Genes: 2064

Variants: A775dupYVMA G776delinsVC

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

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the correlation between the KRAS G12D mutation and response to the therapy bortezomib, indicating that exceptional responses can be achieved in patients with this mutation. Oncogenic: The KRAS G12D mutation is described as a somatic variant that contributes to tumor development in non-small-cell lung cancer (NSCLC) models, indicating its role in oncogenesis.

Gene→Variant (gene-first): 3845:G12D

Genes: 3845

Variants: G12D

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

Evidence Type(s): Functional, Predictive

Justification: Functional: The passage discusses how the variant T790 interacts with the drug TAK-788, specifically mentioning hydrogen bonding and binding modes, indicating an alteration in molecular function. Predictive: The mention of TAK-788 binding to T790 suggests a correlation with therapeutic response, as it implies that the presence of T790 may influence the effectiveness of the treatment.

Gene→Variant (gene-first): 1956:T790

Genes: 1956

Variants: T790

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

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the correlation between the L858R variant and drug sensitivity, indicating that the L858R mutation has a drug-sensitizing effect, which aligns with predictive evidence regarding therapy response. Oncogenic: The L858R variant is implicated in greater potency against EGFR compared to WT EGFR, suggesting its role in tumor development or progression, which is characteristic of oncogenic evidence.

Gene→Variant (gene-first): 1956:L858R

Genes: 1956

Variants: L858R

[Paragraph-level] PMCID: PMC11551396 Section: RESULTS PassageIndex: 7

Evidence Type(s): Predictive, Functional

Justification: Predictive: The passage discusses the measurement of biochemical potencies of EGFR inhibitors against specific mutants, including L858R and L858R/T790M, indicating a correlation with response to therapy. Functional: The passage describes the use of recombinant EGFR kinase proteins in assays to evaluate the biochemical activity of inhibitors, which implies that the variants may alter molecular function.

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

Justification: Predictive: The passage discusses the enhanced inhibitor sensitivity of the L858R variant in relation to its decreased affinity for ATP, indicating a correlation with sensitivity to EGFR TKIs, which aligns with predictive evidence. Oncogenic: The passage implies that the L858R variant contributes to oncogenicity, as it discusses the variant's biochemical properties and their relation to tumor development and progression.

Gene→Variant (gene-first): 1956:L858R

Genes: 1956

Variants: L858R

[Paragraph-level] PMCID: PMC11551396 Section: ABSTRACT PassageIndex: 3

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the drug sensitivity and resistance of the exon 20 insertion variants, indicating their correlation with response to specific therapies, particularly EGFR tyrosine kinase inhibitors. Oncogenic: The passage describes somatic mutations in the EGFR gene, specifically the exon 20 insertion variants, which contribute to tumor development in non-small cell lung cancer.

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

Genes: 1956

Variants: L858R N771insSVD

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

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the effects of anti-HER2 agents on cell proliferation and HER2 phosphorylation in relation to the S310F HER2 mutant, indicating a correlation with response to specific therapies. Oncogenic: The S310F variant is implicated in the phosphorylation process and cell proliferation in cancer cells, suggesting its role in tumor development or progression.

Gene→Variant (gene-first): 2064:S310F

Genes: 2064

Variants: S310F

[Paragraph-level] PMCID: PMC6843359 Section: RESULTS PassageIndex: 3

Evidence Type(s): Predictive, Functional

Justification: Predictive: The passage discusses the binding interactions of various HER2 mutants with the antibodies pertuzumab and trastuzumab, indicating their response to these therapies. Functional: The passage describes the preparation and purification of recombinant fusion proteins and their binding characteristics, which suggests alterations in molecular function related to the HER2 mutants.

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

Justification: Predictive: The passage indicates that the S310F mutant is not reactive to Pertuzumab, suggesting a correlation with resistance to this specific therapy. Functional: The passage discusses the binding characteristics of the S310F mutant, indicating an alteration in molecular function related to its interaction with Trastuzumab.

Gene→Variant (gene-first): 2064:S310F

Genes: 2064

Variants: S310F

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

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the selective inhibitor CHMFL-KIT-031 and its efficacy against the KIT V559D mutation, indicating a correlation with response to therapy. Oncogenic: The KIT V559D mutation is described as a primary gain-of-function mutation in GISTs, suggesting it contributes to tumor development or progression.

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

Genes: 3815

Variants: D816V L576P N822K T670I V559D V654A

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

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the response of the tumor to the treatment with CHMFL-KIT-031, indicating a correlation between the V559D variant and the sensitivity to this specific therapy, as evidenced by tumor growth inhibition. Oncogenic: The V559D variant is implicated in tumor progression, as the passage describes its role in a mouse model where the variant is present and the tumor's response to treatment is evaluated.

Gene→Variant (gene-first): 3815:V559D

Genes: 3815

Variants: V559D

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

Evidence Type(s): Oncogenic, Predictive

Justification: Oncogenic: The variant V559D is discussed in the context of tumor growth inhibition, indicating that it contributes to tumor development or progression in the specified cell model. Predictive: The mention of CHMFL-KIT-031 inhibiting tumor growth suggests a correlation between the V559D variant and response to this specific therapy.

Gene→Variant (gene-first): 3815:V559D

Genes: 3815

Variants: V559D

[Paragraph-level] PMCID: PMC5762309 Section: RESULTS PassageIndex: 9

Evidence Type(s): Predictive, Functional

Justification: Predictive: The passage discusses the inhibitory effect of CHMFL-KIT-031 against the KIT V559D mutant, indicating a correlation with response to therapy, as evidenced by the IC50 values and selectivity over the wild-type KIT. Functional: The variant KIT V559D is shown to alter the molecular function by affecting the phosphorylation of specific sites and downstream mediators, demonstrating its role in biochemical activity as tested in various assays.

Gene→Variant (gene-first): 3815:V559D

Genes: 3815

Variants: V559D

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

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage indicates that CHMFL-KIT-031 selectively inhibits the KIT V559D mutant, suggesting a correlation with response to therapy. Oncogenic: The mention of the KIT V559D mutant in the context of selective inhibition implies that this somatic variant contributes to tumor development or progression.

Gene→Variant (gene-first): 3815:V559D

Genes: 3815

Variants: V559D

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

Evidence Type(s): Predictive, Functional

Justification: Predictive: The passage discusses the binding and selectivity of CHMFL-KIT-031 to the V559D, L576P, and A829P variants, indicating their potential response to therapy, particularly in the context of inhibitor selectivity. Functional: The results indicate that the variants (V559D, L576P, A829P) alter the binding characteristics of the compound CHMFL-KIT-031, suggesting a change in molecular function related to kinase activity.

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

Genes: 3815

Variants: A829P L576P V559D

[Paragraph-level] PMCID: PMC5762309 Section: RESULTS PassageIndex: 3

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the response of various KIT variants, including V559D, L576P, and others, to different therapies such as CHMFL-KIT-031 and Imatinib, indicating their correlation with treatment sensitivity and resistance. Oncogenic: The variants mentioned, particularly V559D and L576P, are described in the context of their role in transforming BaF3 cells, suggesting that they contribute to tumor development or progression.

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

Genes: 3815

Variants: D816V L576P N822K T670I V559D V654A

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

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage indicates that CHMFL-KIT-031 selectively inhibits the proliferation of cells with the V559D variant, suggesting a correlation with response to this specific therapy. Oncogenic: The mention of the V559D variant in the context of inhibiting cell proliferation implies that it contributes to tumor development or progression, as it is associated with a specific cell line used in cancer research.

Gene→Variant (gene-first): 3815:V559D

Genes: 3815

Variants: V559D

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

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the treatment of a patient with advanced colorectal cancer using trastuzumab based on the presence of the ERBB2 p.L755S mutation, indicating a correlation with therapy response. Oncogenic: The mention of the ERBB2 p.L755S mutation as a genetic driver event in the context of advanced colorectal cancer suggests its role in tumor development or progression.

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

Genes: 2064 673 324

Variants: p.L755S p.N581S p.Q1429fs

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

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the treatment response to therapies such as trastuzumab and FOLFIRI, which are influenced by the presence of specific somatic mutations, indicating a correlation between the variants and treatment response. Oncogenic: The passage identifies somatic mutations in the tumors that are associated with tumor development and progression, particularly noting the likely activating mutation in the ERBB2 p.L755S variant.

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

Genes: 673 2064 324

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

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

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the emergence of KRAS mutations associated with treatment resistance, indicating a correlation with response to therapy, specifically in the context of chemotherapy and targeted treatments. Oncogenic: The passage describes the identification of KRAS mutations that contribute to tumor progression, particularly noting the emergence of these mutations prior to disease progression, which is indicative of their role in cancer development.

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

Genes: 3791 3845 4893 79811 673

Variants: A163G G12D G12N G13D Q61H Q61L R106H V600E

[Paragraph-level] PMCID: PMC10011885 Section: RESULTS PassageIndex: 20

Evidence Type(s): Prognostic, Predictive

Justification: Prognostic: The passage discusses how the BRAF V600E mutation VAF ratio correlates with progression-free survival (PFS) and overall survival (OS), indicating that it is associated with disease outcomes independent of therapy. Predictive: The assessment of the BRAF V600E mutation VAF ratio as a predictor of PFS and OS suggests that it may correlate with treatment response, indicating its predictive value in the context 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

Justification: Predictive: The passage discusses how early changes in ctDNA levels, specifically related to the BRAF V600E variant, are predictive of clinical benefit and objective response to combination vemurafenib and erlotinib therapy. Oncogenic: The BRAF V600E variant is implicated in tumor dynamics and is associated with the response to treatment, indicating its role in tumor development or progression.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

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

Evidence Type(s): Predictive, Diagnostic, Oncogenic

Justification: Predictive: The passage indicates that the presence of genetic alterations, including the NRAS G13C mutation, correlates with clinical benefit from treatment, suggesting a predictive relationship regarding therapy response. Diagnostic: The mention of the NRAS G13C mutation being detected in a patient implies its role in identifying or classifying the disease, which aligns with diagnostic evidence. Oncogenic: The NRAS G13C mutation is discussed in the context of being a mutation found in a patient, which suggests its potential role in tumor development or progression.

Gene→Variant (gene-first): 4893:G13C

Genes: 4893

Variants: G13C

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

Evidence Type(s): Predictive, Diagnostic, Oncogenic

Justification: Predictive: The passage discusses the sensitivity of specific EGFR variants (D770 and G770) to various EGFR-TKIs, indicating a correlation with response to therapy. Diagnostic: The mention of EGFR exon 20 insertion mutations and their frequency in lung cancer suggests that these variants are used to classify and define a specific subtype of the disease. Oncogenic: The variants D770 and G770 are described as contributing to tumor development, as they are part of the EGFR mutations associated with lung cancer.

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

Justification: Predictive: The passage indicates that the variant G770 and other exon 20 insertion mutations are sensitive to specific EGFR TKIs, suggesting a correlation with treatment response.

Gene→Variant (gene-first): 1956:G770

Genes: 1956

Variants: G770

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

Evidence Type(s): Predictive, Diagnostic

Justification: Predictive: The passage discusses the correlation between the G770 variant and radiographic responses to therapies (poziotinib and mobocertinib) in advanced lung cancers, indicating its predictive nature regarding treatment response. Diagnostic: The mention of "EGFR exon 20 insertion mutations with G770 equivalence" suggests that the G770 variant is used to classify or define a specific subtype of lung cancer, supporting its role as a diagnostic marker.

Gene→Variant (gene-first): 1956:G770

Genes: 1956

Variants: G770

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

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the response of patients with metastatic lung cancers harboring EGFR exon 20 insertion mutations, including G770, to various EGFR TKIs, indicating a correlation with treatment response. Oncogenic: The mention of tumors harboring EGFR exon 20 insertion mutations, including G770, suggests that this somatic variant contributes to tumor development or progression in the context of 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

Justification: Predictive: The passage discusses the potential response of patients with advanced lung cancers harboring the G770 variant to specific therapies, indicating a correlation with treatment response.

Gene→Variant (gene-first): 1956:G770

Genes: 1956

Variants: G770

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

Evidence Type(s): Predictive, Functional

Justification: Predictive: The passage discusses the sensitivity of the V769dupASV variant to 2nd generation EGFR TKIs, indicating a correlation with response to therapy. Functional: The variant V769dupASV is shown to alter the biochemical function of EGFR, as evidenced by the differing levels of 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

Justification: Predictive: The passage discusses the response of cells with the A767_V769dupASV mutant to specific therapies (afatinib and dacomitinib), indicating a correlation between the variant and treatment sensitivity. Oncogenic: The variant A767_V769dupASV is mentioned in the context of proliferation assays, suggesting that it contributes to tumor development or progression in the tested cell lines.

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

Genes: 1956

Variants: V769dupASV

[Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 5

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the sensitivity and resistance of various EGFR mutations, including D770_N771insSVD, V769dupASV, and Y764insFQEA, to different EGFR TKIs, indicating a correlation with response to therapy. Oncogenic: The variants mentioned are associated with the development of cancer, as they are described in the context of a Ba/F3 cell line model driven by specific EGFR mutations, which contribute to tumor behavior.

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

Justification: Predictive: The passage discusses the clinical benefit of dabrafenib plus trametinib in BRAF V600E-mutant ATC, indicating a correlation with improved treatment response. Prognostic: The mention of improved long-term survival in patients with BRAF V600E-mutant ATC suggests a correlation with disease outcome independent of therapy.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

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

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the evaluation of dabrafenib plus trametinib in patients with BRAF V600E-mutant cancers, indicating a correlation with treatment response. Oncogenic: The mention of BRAF V600E in the context of a study for rare cancers suggests that this somatic variant contributes to tumor development or progression.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

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

Evidence Type(s): Predictive, Diagnostic

Justification: Predictive: The passage discusses the approval of combined therapy with dabrafenib plus trametinib for treatment of BRAF V600E-mutant anaplastic thyroid cancer, indicating a correlation with treatment response. Diagnostic: The mention of BRAF V600E as a specific mutation in anaplastic thyroid cancer suggests its role in defining or classifying the disease subtype.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

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

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses T790M as a resistance mechanism to first-generation EGFR tyrosine kinase inhibitors, indicating its correlation with treatment response. Oncogenic: The mention of T790M in the context of an acquired resistance mechanism suggests that it contributes to tumor progression in EGFR-mutated NSCLC.

Gene→Variant (gene-first): 1956:T790M

Genes: 1956

Variants: T790M

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

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the T790M variant as a potential resistance mechanism to icotinib treatment, indicating its correlation with treatment response. Oncogenic: The L858R variant is described as being present in a patient with lung adenocarcinoma, suggesting its role in tumor development or progression.

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

Genes: 1956

Variants: L858R T790M

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

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the variant G2032R in the context of acquired resistance mutations and mentions the overall responses and prolonged progression-free survival (PFS) associated with taletrectinib, indicating a correlation with treatment response. Oncogenic: The mention of G2032R as an acquired resistance mutation suggests that it contributes to tumor development or progression, particularly in the context of therapy resistance.

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

Genes: 6098

Variants: G2032R

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

Evidence Type(s): Predictive

Justification: Predictive: The passage indicates that 67% of patients with G2032R mutations responded to treatment, suggesting a correlation between the variant and treatment response.

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

Genes: 6098

Variants: G2032R

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

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the activity of taletrectinib against the G2032R variant, highlighting its correlation with high response rates and prolonged progression-free survival, indicating predictive evidence related to therapy response. Oncogenic: The mention of the G2032R variant in the context of ROS1+ non-small cell lung cancer suggests that it may contribute to tumor development or progression, aligning with oncogenic evidence.

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

Genes: 6098

Variants: G2032R

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

Evidence Type(s): Oncogenic, Predictive

Justification: Oncogenic: The variant p.L1363P is shown to disrupt the interaction with PALB2 and leads to the development of mammary tumors, indicating its contribution to tumor development. Predictive: The passage states that Brca1 p.L1363P mammary tumors are responsive to cisplatin and PARP inhibition, suggesting a correlation with treatment response.

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

Genes: 7158

Variants: p.L1363P

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

Evidence Type(s): Predictive, Oncogenic, Functional

Justification: Predictive: The passage discusses the response of KB1(L1363P)P mammary tumors to targeted therapies, indicating that these tumors responded significantly better to cisplatin and the PARP inhibitor AZD2461, which correlates the variant with treatment response. Oncogenic: The variant is associated with tumor development and progression, as it is discussed in the context of mammary tumors and their response to therapies, suggesting a role in cancer biology. Functional: The passage describes how the variant affects the ability of tumor cells to induce RAD51 foci in response to gamma-radiation, indicating an alteration in molecular function related to DNA repair mechanisms.

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

Justification: Predictive: The variant L1363P is associated with a response to cisplatin and PARP inhibition, indicating its correlation with treatment sensitivity.

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

Genes: 7158

Variants: L1363P

[Paragraph-level] PMCID: PMC7612117 Section: RESULTS PassageIndex: 9

Evidence Type(s): Predictive, Functional

Justification: Predictive: The passage discusses increased sensitivity to cisplatin and PARP1 inhibition in the context of the Brca1 p.L1363P variant, indicating a correlation with treatment response. Functional: The variant p.L1363P is shown to severely attenuate BRCA1-PALB2 binding, which alters the molecular function related to homologous recombination repair (HRR).

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

Justification: Predictive: The passage discusses the acquired T790M mutation in the context of EGFR-TKI resistance, indicating a correlation with treatment resistance. Oncogenic: The T790M mutation is described as contributing to EGFR-TKI resistance, which is a characteristic of tumor progression in the context of cancer.

Gene→Variant (gene-first): 1956:T790M

Genes: 1956

Variants: T790M

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

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the potential vulnerability of the malignancy to BRAF inhibition, indicating a correlation between the BRAF p.V600E mutation and response to therapy with dabrafenib and trametinib. Oncogenic: The BRAF p.V600E mutation is implicated in the malignancy's development and progression, as it is associated with the treatment approach and the observed tumor response to therapy.

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, Oncogenic

Justification: Predictive: The passage discusses the sensitivity of D835 mutants to type II inhibitors, indicating a correlation with treatment response, which aligns with predictive evidence. Oncogenic: The mention of D835 mutations and their role in mediating resistance and sensitivity to FLT3 TKIs suggests that these somatic variants contribute to tumor development or progression.

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

Justification: Predictive: The passage discusses the D835H mutation's resistance to type II inhibitors, indicating a correlation with treatment response and sensitivity to specific therapies. Functional: The passage describes how the D835H mutation alters the binding mode and hydrogen bond formation, indicating a change in molecular function related to inhibitor interaction.

Gene→Variant (gene-first): 2322:D835H

Genes: 2322

Variants: D835H

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

Evidence Type(s): Functional, Predictive

Justification: Functional: The passage discusses how the D835E/N mutations alter molecular interactions, specifically the formation of hydrogen bonds and the conservation of the alpha-helix structure, which affects inhibitor binding. Predictive: The passage indicates that the D835E/N variants are associated with sensitivity to type II inhibitors, suggesting a correlation with treatment response.

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

Genes: 2322

Variants: D835 D835E/N

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

Evidence Type(s): Predictive, Functional

Justification: Predictive: The passage discusses the correlation of D835 mutations with resistance to type II inhibitors, indicating a relationship between the variant and treatment response. Functional: The passage describes the impact of D835 mutations on the short alpha-helix and its potential effect on the drug-binding site, suggesting an alteration in molecular function related to drug interaction.

Gene→Variant (gene-first): 2322:D835

Genes: 2322

Variants: D835

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

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses how various D835 substitutions correlate with resistance to FLT3 inhibitors, indicating their predictive value regarding treatment response. Oncogenic: The D835 mutations are reported to cause resistance in patients, suggesting that these somatic variants contribute to tumor development or progression.

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

Justification: Oncogenic: The variant p.K656E is described as an activating and transforming mutation, indicating its role in tumor development or progression. Predictive: The variant p.V561M is mentioned as imparting 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, Oncogenic

Justification: Predictive: The passage discusses the potential use of FGFR inhibitors in combination with other treatments, indicating a correlation with therapy response. Oncogenic: The mention of mutations in the context of a tumor suggests that the variants may contribute to tumor development or progression.

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

Justification: Oncogenic: The passage describes p.K656E as a known hotspot mutation that is activating and transforming, indicating its role in tumor development or progression. Predictive: The passage mentions that p.V561M is described as a gatekeeper mutation imparting resistance to FGFR inhibitors, which correlates with treatment 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, Oncogenic

Justification: Predictive: The passage discusses the response of the patient to chemotherapy treatment and how the presence of the D835Y mutation correlates with the patient's relapse, indicating its potential role in therapeutic decisions. Oncogenic: The D835Y mutation is described as a mutation that contributes to the tumor's behavior, particularly in the context of the patient's relapse and the increase in the mutated clone's percentage.

Gene→Variant (gene-first): 2322:D835Y

Genes: 2322

Variants: D835Y

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

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the resistance of the D835Y variant to conventional induction chemotherapy and indicates that the treatment successfully inhibited the D835Y mutated clone, suggesting a correlation with treatment response. Oncogenic: The D835Y variant is mentioned in the context of tumor progression and its behavior in response to treatment, indicating its role in tumor development or progression.

Gene→Variant (gene-first): 2322:D835Y

Genes: 2322

Variants: D835Y

[Paragraph-level] PMCID: PMC4741605 Section: RESULTS PassageIndex: 18

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage states that the mutations D839G and D835H are able to confer resistance to Sorafenib treatment, indicating a correlation between these variants and treatment response. Oncogenic: The presence of the D839G and D835H mutations is associated with the evolution of the FLT3 ITD+ clone and suggests a role in tumor development or progression, particularly in the context of acute myeloid leukemia (AML).

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

Genes: 2322

Variants: D835H D839G

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

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the patient's response to the FLT3 inhibitor AC220-002, indicating that the presence of the D835Y and D839G variants may correlate with the patient's treatment response. Oncogenic: The D835Y and D839G variants are mentioned in the context of their abundance in the patient's sample, suggesting their potential role in tumor development or progression as part of the FLT3 mutation landscape.

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

Genes: 2322

Variants: D835Y D839G

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

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses how the G1202R and L1196M mutations are major resistance mechanisms to ALK inhibitors, indicating that these variants correlate with resistance to specific therapies. Oncogenic: The G1202R and L1196M mutations are described as resistance mechanisms that contribute to tumor progression, particularly in the context of ALK inhibitors, suggesting their role in oncogenesis.

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

Genes: 238

Variants: G1202R L1196M

[Paragraph-level] PMCID: PMC9398166 Section: RESULTS PassageIndex: 12

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the correlation of TPX-0131 treatment with tumor growth inhibition and suppression of ALK phosphorylation, indicating that the G1202R, L1196M, and L1198F variants are associated with resistance to therapy and response to treatment. Oncogenic: The variants G1202R, L1196M, and L1198F are described in the context of ALK resistance mutations, suggesting their role in tumor development or progression as they are associated with the EML4-ALK fusion in a cancer model.

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, Oncogenic

Justification: Predictive: The passage discusses the response of tumor models harboring specific ALK mutations (G1202R, L1196M, L1198F) to the therapy TPX-0131, indicating a correlation between the variants and treatment efficacy. Oncogenic: The variants G1202R, L1196M, and L1198F are described in the context of tumor models, suggesting that they contribute to tumor development or progression as part of the EML4-ALK fusion.

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

Justification: Predictive: The passage discusses how the variants G1202R, L1196M, and L1198F correlate with the response to the ALK inhibitor TPX-0131, indicating their role in resistance to therapy. Oncogenic: The variants mentioned are part of ALK oncogenic fusion proteins, which are implicated in tumor development and progression, as evidenced by their evaluation in assays measuring ALK autophosphorylation.

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, Oncogenic

Justification: Predictive: The passage discusses the response of the ALK G1202R/G1269A/L1204V triple mutation to the TPX-0131 inhibitor, indicating a correlation with treatment sensitivity. Oncogenic: The mention of the EML4-ALK compound mutations, including G1202R, G1269A, and L1204V, in the context of cell proliferation assays suggests that these somatic variants contribute to tumor development or progression.

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

Genes: 238

Variants: G1202R G1269A L1204V

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

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the potency of TPX-0131 against various ALK mutations, indicating that the variant mutations correlate with the response to the therapy, specifically highlighting the differences in inhibition potency against different mutations. Oncogenic: The passage describes the use of engineered Ba/F3 cells expressing oncogenic EML4-ALK variants, indicating that these mutations contribute to tumor development or progression, as they are associated with resistance to ALK inhibitors.

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

Genes: 238

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

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

Evidence Type(s): Predictive, Functional

Justification: Predictive: The passage discusses the potency of TPX-0131 against various ALK mutations, indicating its effectiveness as a therapy for these specific variants, which correlates with treatment response. Functional: The passage describes the biochemical characterization of TPX-0131's inhibition of ALK mutations, focusing on its molecular properties and binding interactions that alter the function of the ALK protein.

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

Justification: Predictive: The passage discusses resistance mutations, including G1202, in the context of second-generation ALK inhibitors and their reduced potency, indicating a correlation with treatment response. Oncogenic: The mention of G1202 as a resistance mutation suggests that it contributes to tumor development or progression by obstructing binding and reducing the efficacy of ALK inhibitors.

Gene→Variant (gene-first): 238:G1202

Genes: 238

Variants: G1202

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

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses how the BRAFV600E variant correlates with venetoclax resistance, indicating a relationship between the variant and treatment response. Oncogenic: The passage describes the overexpression of the mutated BRAF (p.V600E) in a cell line, which is associated with increased resistance to venetoclax, suggesting that this somatic variant contributes to tumor progression.

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

Genes: 673 7157

Variants: BRAFV600E p.V600E p.W110*

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

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the SF3B1 mutations in the context of venetoclax exposure and resistance, indicating a correlation between these variants and treatment response. Oncogenic: The SF3B1 mutations are described as evolving during treatment and being selected for during venetoclax therapy, suggesting their role in tumor development or progression.

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

Genes: 23451

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

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

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the selection of specific mutations (including p.K601E and p.Q547fs) during venetoclax therapy, indicating a correlation with treatment response. Oncogenic: The mutations p.K601E and p.S321fs are described as contributing to tumor development, as they are retained in the clonal evolution of the cancer during relapse.

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

Genes: 673 330 58508

Variants: p.K601E p.Q547fs p.S321fs

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

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the involvement of BTG1 mutations (p.E46K and p.Q36H) in the resistance to venetoclax treatment, indicating a correlation between these variants and treatment response. Oncogenic: The passage describes the BTG1 mutations as being involved in the clonal evolution towards therapy resistance, suggesting that these somatic variants contribute to tumor development or 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

Justification: Oncogenic: The passage states that the BRAF (p.K601E) mutation was shown to be oncogenic and can be targeted by MEK inhibitors, indicating its role in tumor development or progression. Predictive: The mention of patients responding to venetoclax therapy, even with the presence of the BRAF mutation, suggests a correlation with treatment response, which aligns with predictive evidence.

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

Genes: 673

Variants: p.K601E

[Paragraph-level] PMCID: PMC7294133 Section: RESULTS PassageIndex: 16

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage indicates that treatment with TK inhibitors has a positive effect on the phenotype induced by the EPHB4-V871I variant, suggesting a correlation with response to therapy. Oncogenic: The mention of the EPHB4-V871I variant inducing a phenotype in neuroblastoma (NB) cell lines implies that it contributes to tumor development or progression.

Gene→Variant (gene-first): 2050:V871I

Genes: 2050

Variants: V871I

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

Evidence Type(s): Predictive, Prognostic

Justification: Predictive: The passage discusses the response to therapy involving SRA737 and PARP inhibitors (PARPi), indicating a correlation with treatment response in specific PDX models. Prognostic: The mention of a trending increase in survival with combination therapy compared to monotherapy suggests a correlation with disease outcome, although it did not reach statistical significance.

Gene→Variant (gene-first): 142:S4D

Genes: 142

Variants: S4D

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

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses how the variants T790M, C797S/G, and L718V/Q are associated with resistance mechanisms to EGFR-TKIs, indicating their role in treatment response. Oncogenic: The variants mentioned are described as second-site mutations that contribute to resistance in the context of tumor development and progression in NSCLC.

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, Oncogenic

Justification: Predictive: The passage discusses the correlation between PIK3CA mutations (H1047R, E545K, E542K) and the response to the therapy everolimus, indicating that these variants are associated with treatment outcomes. Oncogenic: The mention of PIK3CA mutations in the context of tumor analysis suggests that these somatic variants contribute to tumor development or progression, particularly in relation to their response to therapy.

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): Predictive, Prognostic

Justification: Predictive: The passage suggests that patients with E545K/E542K mutations had shorter progression-free survival (PFS) and overall survival, indicating a potential role of these mutations in resistance to hormone therapy. Prognostic: The mention of shorter PFS and overall survival in patients with the E545K/E542K mutations indicates a correlation with disease outcome independent of therapy.

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, Oncogenic

Justification: Predictive: The passage discusses the correlation between PIK3CA mutations (H1047R, E545K, E542K) and the efficacy of everolimus, indicating that these variants are associated with prolonged progression-free survival (PFS) in patients treated with this therapy. Oncogenic: The mention of PIK3CA mutations in the context of their role in tumor development and the efficacy of a cancer treatment suggests that these somatic variants contribute to tumor progression.

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

Genes: 5290

Variants: E542K E545K H1047R

[Paragraph-level] PMCID: PMC5355930 Section: RESULTS PassageIndex: 3

Evidence Type(s): Diagnostic, Predictive

Justification: Diagnostic: The passage discusses the prevalence of PIK3CA mutations, including specific variants, in a patient population, indicating their association with the disease context. Predictive: The mention of higher prevalence of PIK3CA mutations in the everolimus arm compared to the placebo arm suggests a correlation with treatment response, indicating predictive value.

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): Predictive, Oncogenic

Justification: Predictive: The T733I mutation is associated with resistance to lapatinib and sensitivity to adavosertib, indicating its role in predicting treatment response. Oncogenic: The T733I mutation is described as weakly transforming, suggesting it contributes to tumor development or progression in the context of the PDX model.

Gene→Variant (gene-first): 2064:T733I

Genes: 2064

Variants: T733I

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

Evidence Type(s): Oncogenic, Predictive

Justification: Oncogenic: The TP53 Y220C missense mutation is described as a "deleterious somatic mutation," indicating its contribution to tumor development or progression. Predictive: The passage discusses the patient's response to various therapies, including PARP inhibitors and the M6620-carboplatin combination therapy, suggesting that the Y220C variant may correlate with treatment response.

Gene→Variant (gene-first): 7157:Y220C

Genes: 7157

Variants: Y220C

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

Evidence Type(s): Predictive, Prognostic, Oncogenic

Justification: Predictive: The passage indicates that none of the patients with the BRAF V600E mutation responded to the treatment, suggesting a correlation between the variant and resistance to therapy. Prognostic: The passage reports that BRAF mutation is associated with significantly shorter overall survival (OS) and a trend towards shorter progression-free survival (PFS), indicating its impact on disease outcome independent of therapy. Oncogenic: The BRAF V600E mutation is described as a somatic variant that is part of the study population's tumor mutations, contributing to tumor development or progression.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paragraph-level] PMCID: PMC7099049 Section: RESULTS PassageIndex: 9

Evidence Type(s): Prognostic, Predictive

Justification: Prognostic: The passage discusses the ability of a model to predict survival in HNSCC, indicating a correlation between the variant and disease outcome. Predictive: The mention of using NRG in a prediction model for HNSCC survival suggests a relationship with treatment response or sensitivity, aligning with predictive evidence.

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

Justification: Predictive: The passage discusses the association of the R108K variant with clinical responses to EGFR kinase inhibitors, indicating a correlation with treatment response. Oncogenic: The R108K variant is identified in gliomas, suggesting its potential role in tumor development or progression, particularly in the context of EGFR amplification.

Gene→Variant (gene-first): 1956:R108K

Genes: 1956

Variants: R108K

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

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses how the presence of EGFR missense mutants, including L858R and L861Q, may sensitize transformed cells to EGFR kinase inhibitors, indicating a correlation with treatment response. Oncogenic: The identical missense mutations are described as having oncogenicity and playing a role in gliomagenesis, suggesting that these somatic variants contribute to tumor development.

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

Genes: 1956

Variants: L858R L861Q T790M