[Paragraph-level] PMCID: PMC2837563 Section: RESULTS PassageIndex: 11

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: A146T | Summary: The A146T mutation is shown to be in the active GTP-bound conformation, indicating an alteration in molecular function. Evidence Type: Functional | Mutation: G12V | Summary: The G12V mutation is identified as being in the active GTP-bound conformation, suggesting a change in molecular function. Evidence Type: Functional | Mutation: K117N | Summary: The K117N mutation is confirmed to be in the active GTP-bound conformation, reflecting an alteration in molecular function. Evidence Type: Functional | Mutation: L19F | Summary: The L19F mutation is demonstrated to be in the active GTP-bound conformation, indicating a change in molecular function.

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

Genes: 3845

Variants: A146T G12V K117N L19F R164Q

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

Evidence Type(s): Oncogenic

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

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

Genes: 3845

Variants: A146T G12D G12V G13D K117N L19F Q61H R164Q

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

Evidence Type(s): Oncogenic

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

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

Genes: 3845 673

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

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

Evidence Type(s): Oncogenic

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

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

Genes: 673 3845

Variants: G57T Leu19Phe V600E

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

Evidence Type(s): Predictive, Functional

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

Gene→Variant (gene-first): 142:S4D

Genes: 142

Variants: S4D

[Paragraph-level] PMCID: PMC11253285 Section: RESULTS PassageIndex: 15

Evidence Type(s): None

Summary: Not enough information in this passage.

Gene→Variant (gene-first): 1111:S3C

Genes: 1111

Variants: S3C

[Paragraph-level] PMCID: PMC9441062 Section: RESULTS PassageIndex: 15

Evidence Type(s): Prognostic

Summary: Evidence Type: Prognostic | Mutation: L858R | Summary: The L858R mutation is associated with prognosis in NSCLC patients, as indicated by the analysis of progression-free survival (PFS) among patients with this mutation compared to wild-type counterparts.

Gene→Variant (gene-first): 1956:L858R

Genes: 1956

Variants: L858R

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

Evidence Type(s): Predictive

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

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

Genes: 1956

Variants: C797S/G L718V/Q T790M

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

Evidence Type(s): Oncogenic

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

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

Genes: 1956

Variants: G719C L858R S768I

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

Evidence Type(s): Predictive

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

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

Genes: 5290

Variants: E542K E545K H1047R

[Paragraph-level] PMCID: PMC5355930 Section: ABSTRACT PassageIndex: 4

Evidence Type(s): Diagnostic

Summary: Evidence Type: Diagnostic | Mutation: H1047R | Summary: The H1047R mutation is used to define patient subgroups based on PIK3CA mutations in the context of treatment analysis. Evidence Type: Diagnostic | Mutation: E545K | Summary: The E545K mutation is used to define patient subgroups based on PIK3CA mutations in the context of treatment analysis. Evidence Type: Diagnostic | Mutation: E542K | Summary: The E542K mutation is used to define patient subgroups based on PIK3CA mutations in the context of treatment analysis.

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

Genes: 5290

Variants: E542K E545K H1047R

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

Evidence Type(s): Prognostic, Predictive

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

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

Genes: 5290

Variants: E542K E545K

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

Evidence Type(s): Predictive

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

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

Genes: 5290

Variants: E542K E545K H1047R

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

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: H1047R | Summary: The H1047R mutation is identified as a prevalent PIK3CA HS mutation in patients, indicating its contribution to tumor development or progression. Evidence Type: Oncogenic | Mutation: E545K | Summary: The E545K mutation is noted as one of the prevalent PIK3CA HS mutations, suggesting its role in tumor development or progression. Evidence Type: Oncogenic | Mutation: E542K | Summary: The E542K mutation is mentioned as a prevalent PIK3CA HS mutation, indicating its involvement in tumor development or progression.

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

Genes: 5290

Variants: E542K E545K H1047R

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

Evidence Type(s): Oncogenic, Predictive

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

Gene→Variant (gene-first): 2064:T733I

Genes: 2064

Variants: T733I

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

Evidence Type(s): Oncogenic

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

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

Genes: 2064

Variants: G778A V777L

[Paragraph-level] PMCID: PMC10618648 Section: RESULTS PassageIndex: 11

Evidence Type(s): None

Summary: Not enough information in this passage.

Gene→Variant (gene-first): 2064:E in 72

Genes: 2064

Variants: E in 72

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

Evidence Type(s): Oncogenic

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

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

Genes: 3021 673

Variants: p.K27M p.V600E

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

Evidence Type(s): Oncogenic, Functional

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

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

Genes: 1106 1029 3417 23152

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

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

Evidence Type(s): Oncogenic

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

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

Genes: 3021 673

Variants: p.K27M p.V600E

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

Evidence Type(s): Oncogenic

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

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

Genes: 3845 673

Variants: G12D G12V Q636X V600E

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

Evidence Type(s): Functional, Oncogenic

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

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

Genes: 4436

Variants: p.Ala636Pro

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

Evidence Type(s): Oncogenic

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

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

Genes: 4436

Variants: p.Ala636Pro

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

Evidence Type(s): Functional, Oncogenic

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

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

Genes: 4436

Variants: p.Ala636Pro

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

Evidence Type(s): Functional, Oncogenic

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

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

Genes: 4436

Variants: p.Ala636Pro

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

Evidence Type(s): Oncogenic, Functional

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

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

Genes: 780 207 405 3084 2048 5156 208 3169 2064

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

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

Evidence Type(s): Functional, Oncogenic

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

Gene→Variant (gene-first): 2625:M294K

Genes: 2625

Variants: M294K

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

Evidence Type(s): Oncogenic

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

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

Genes: 186

Variants: R251H V184I

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

Evidence Type(s): Oncogenic, Functional

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

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

Genes: 9757 23451 4216 861 1588 51742

Variants: G168E K666Q K700E N104S R166Q R169K S184L

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

Evidence Type(s): Oncogenic, Functional

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

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

Genes: 5290 5295

Variants: C420R E545K G1049R H1047L H1047R M1043I N564D

[Paragraph-level] PMCID: PMC7226056 Section: RESULTS PassageIndex: 7

Evidence Type(s): None

Summary: Not enough information in this passage.

Gene→Variant (gene-first): 7015:tryptophan-aspartic acid 40

Genes: 7015

Variants: tryptophan-aspartic acid 40

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

Evidence Type(s): Oncogenic

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

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

Genes: 7015

Variants: CGGA 94) in the TCGA

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

Evidence Type(s): Oncogenic

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

Gene→Variant (gene-first): 7157:Y220C

Genes: 7157

Variants: Y220C

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

Evidence Type(s): Predictive, Prognostic, Oncogenic

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

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

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

Evidence Type(s): Oncogenic, Functional

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

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

Genes: 2064 673 324

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

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

Evidence Type(s): Oncogenic

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

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

Genes: 673 2064 324

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

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

Evidence Type(s): Oncogenic

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

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

Genes: 3417

Variants: p.R132H

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

Evidence Type(s): Predictive, Oncogenic

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

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

Genes: 6098

Variants: G2032R

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

Evidence Type(s): Oncogenic, Predisposing

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

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

Genes: 79728 3845

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

[Paragraph-level] PMCID: PMC7099049 Section: RESULTS PassageIndex: 13

Evidence Type(s): Functional, Prognostic

Summary: Evidence Type: Functional | Mutation: rs16879870 | Summary: The allele A of rs16879870 is associated with an increased mRNA expression level of gene GJB7, indicating a potential functional impact on gene expression. Evidence Type: Functional | Mutation: rs854936 | Summary: The allele C of rs854936 is associated with an increased mRNA level of gene RTN4R, suggesting a functional role in gene expression. Evidence Type: Prognostic | Mutation: rs16879870 | Summary: Higher expression of GJB7 in cancer tissues correlates with worse prognosis in HNSCC patients, indicating a prognostic significance of this variant. Evidence Type: Prognostic | Mutation: rs854936 | Summary: Increased expression of RTN4R in cancer tissues is associated with worse prognosis in HNSCC patients, highlighting its prognostic relevance.

Gene→Variant (gene-first): NA:rs16879870 NA:rs854936

Genes: NA

Variants: rs16879870 rs854936

[Paragraph-level] PMCID: PMC7099049 Section: RESULTS PassageIndex: 11

Evidence Type(s): Prognostic

Summary: Evidence Type: Prognostic | Mutation: rs2761591 | Summary: The variant rs2761591 is associated with death in head and neck squamous cell carcinoma (HNSCC), indicating its potential role in disease outcome independent of therapy.

Gene→Variant (gene-first): 341019:rs2761591

Genes: 341019

Variants: rs2761591

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

Evidence Type(s): Prognostic, Predictive

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

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

Genes: 2264

Variants: AUC from 0

[Paragraph-level] PMCID: PMC7099049 Section: RESULTS PassageIndex: 7

Evidence Type(s): Prognostic

Summary: Evidence Type: Prognostic | Mutation: rs16879870 | Summary: The variant rs16879870 is associated with an increased risk of death in patients with HNSCC, indicating its prognostic value in survival outcomes. Evidence Type: Prognostic | Mutation: rs2641256 | Summary: The variant rs2641256 contributes to the risk of death in HNSCC patients, suggesting it has prognostic implications for survival. Evidence Type: Prognostic | Mutation: rs2761591 | Summary: The variant rs2761591 is linked to an increased hazard of death in HNSCC, highlighting its role as a prognostic marker. Evidence Type: Prognostic | Mutation: rs854936 | Summary: The variant rs854936 is associated with a higher risk of death in HNSCC patients, indicating its prognostic significance in survival analysis.

Gene→Variant (gene-first): NA:rs16879870 388325:rs2641256 341019:rs2761591 NA:rs854936

Genes: NA 388325 341019

Variants: rs16879870 rs2641256 rs2761591 rs854936

[Paragraph-level] PMCID: PMC7099049 Section: RESULTS PassageIndex: 6

Evidence Type(s): Prognostic

Summary: Evidence Type: Prognostic | Mutation: rs16879870 | Summary: The genotypes CA+AA of rs16879870 are associated with a decreased survival time in patients, indicating a correlation with disease outcome independent of therapy. Evidence Type: Prognostic | Mutation: rs2641256 | Summary: The genotype AA of rs2641256 is associated with an increased death risk in HNSCC, suggesting a correlation with disease outcome independent of therapy. Evidence Type: Prognostic | Mutation: rs2761591 | Summary: The genotype GA of rs2761591 is linked to an increased risk of overall death, indicating a correlation with disease outcome independent of therapy. Evidence Type: Prognostic | Mutation: rs854936 | Summary: The genotype AC of rs854936 is associated with an increased risk of overall death, suggesting a correlation with disease outcome independent of therapy.

Gene→Variant (gene-first): NA:rs16879870 388325:rs2641256 341019:rs2761591 NA:rs854936

Genes: NA 388325 341019

Variants: rs16879870 rs2641256 rs2761591 rs854936

[Paragraph-level] PMCID: PMC7099049 Section: RESULTS PassageIndex: 5

Evidence Type(s): Prognostic

Summary: Evidence Type: Prognostic | Mutation: rs16879870 | Summary: The variant rs16879870 is significantly correlated with HNSCC patients' survival, indicating its potential role as a prognostic marker. Evidence Type: Prognostic | Mutation: rs2641256 | Summary: The variant rs2641256 shows a significant association with HNSCC patients' survival, suggesting it may serve as a prognostic indicator. Evidence Type: Prognostic | Mutation: rs2761591 | Summary: The variant rs2761591 is correlated with HNSCC patients' survival, highlighting its potential prognostic value. Evidence Type: Prognostic | Mutation: rs854936 | Summary: The variant rs854936 demonstrates a significant correlation with HNSCC patients' survival, indicating its relevance as a prognostic factor.

Gene→Variant (gene-first): NA:rs16879870 388325:rs2641256 341019:rs2761591 NA:rs854936

Genes: NA 388325 341019

Variants: rs16879870 rs2641256 rs2761591 rs854936

[Paragraph-level] PMCID: PMC7099049 Section: ABSTRACT PassageIndex: 4

Evidence Type(s): Prognostic

Summary: Evidence Type: Prognostic | Mutation: rs16879870 | Summary: The SNP rs16879870 is suggested to correlate with disease outcome in head and neck squamous cell carcinoma (HNSCC). Evidence Type: Prognostic | Mutation: rs2641256 | Summary: The SNP rs2641256 is suggested to correlate with disease outcome in head and neck squamous cell carcinoma (HNSCC). Evidence Type: Prognostic | Mutation: rs2761591 | Summary: The SNP rs2761591 is suggested to correlate with disease outcome in head and neck squamous cell carcinoma (HNSCC). Evidence Type: Prognostic | Mutation: rs854936 | Summary: The SNP rs854936 is suggested to correlate with disease outcome in head and neck squamous cell carcinoma (HNSCC).

Gene→Variant (gene-first): NA:rs16879870 388325:rs2641256 341019:rs2761591 NA:rs854936

Genes: NA 388325 341019

Variants: rs16879870 rs2641256 rs2761591 rs854936

[Paragraph-level] PMCID: PMC7099049 Section: ABSTRACT PassageIndex: 3

Evidence Type(s): Prognostic, Functional

Summary: Evidence Type: Prognostic | Mutation: rs16879870 | Summary: The variant rs16879870 is significantly associated with HNSCC survival, indicating its correlation with disease outcome independent of therapy. Evidence Type: Prognostic | Mutation: rs2641256 | Summary: The variant rs2641256 is significantly associated with HNSCC survival, suggesting it correlates with disease outcome independent of therapy. Evidence Type: Prognostic | Mutation: rs2761591 | Summary: The variant rs2761591 is significantly associated with HNSCC survival, indicating its correlation with disease outcome independent of therapy. Evidence Type: Prognostic | Mutation: rs854936 | Summary: The variant rs854936 is significantly associated with HNSCC survival, suggesting it correlates with disease outcome independent of therapy. Evidence Type: Functional | Mutation: rs16879870 | Summary: The genotype of rs16879870 is significantly associated with the expression of the gene GJB7 in cancer tissues, indicating an alteration in molecular function. Evidence Type: Functional | Mutation: rs854936 | Summary: The genotype of rs854936 is significantly associated with the expression of the gene RTN4R in cancer tissues, indicating an alteration in molecular function.

Gene→Variant (gene-first): NA:rs16879870 388325:rs2641256 341019:rs2761591 NA:rs854936

Genes: NA 388325 341019

Variants: rs16879870 rs2641256 rs2761591 rs854936

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

Evidence Type(s): Predictive, Oncogenic

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

Gene→Variant (gene-first): 1956:R108K

Genes: 1956

Variants: R108K

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

Evidence Type(s): Oncogenic, Predictive

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

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

Genes: 1956

Variants: L858R L861Q T790M

[Paragraph-level] PMCID: PMC1702556 Section: RESULTS PassageIndex: 14

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: A289V | Summary: The A289V mutation alters molecular function, as it is associated with increased tyrosine phosphorylation in response to EGF stimulation in murine hematopoietic cells. Evidence Type: Functional | Mutation: G598V | Summary: The G598V mutation alters molecular function, as it is associated with increased tyrosine phosphorylation in response to EGF stimulation in murine hematopoietic cells. Evidence Type: Functional | Mutation: L861Q | Summary: The L861Q mutation alters molecular function, as it is associated with increased tyrosine phosphorylation in response to EGF stimulation in murine hematopoietic cells. Evidence Type: Functional | Mutation: R108K | Summary: The R108K mutation alters molecular function, as it is associated with increased tyrosine phosphorylation in response to EGF stimulation in murine hematopoietic cells. Evidence Type: Functional | Mutation: T263P | Summary: The T263P mutation alters molecular function, as it is associated with increased tyrosine phosphorylation in response to EGF stimulation in murine hematopoietic cells.

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

Genes: 1956

Variants: A289V G598V L861Q R108K T263P

[Paragraph-level] PMCID: PMC1702556 Section: RESULTS PassageIndex: 13

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: A289V | Summary: The A289V mutation in EGFR shows a marked increase in receptor autophosphorylation, indicating an alteration in molecular function. Evidence Type: Functional | Mutation: T263P | Summary: The T263P mutation in EGFR is part of a panel of missense mutants that exhibit increased phosphotyrosine content, suggesting a change in biochemical function. Evidence Type: Functional | Mutation: G598V | Summary: The G598V mutation is included in a panel of EGFR missense mutants that demonstrate increased phosphotyrosine content, indicating a functional alteration. Evidence Type: Functional | Mutation: L861Q | Summary: The L861Q mutation is part of a group of EGFR missense mutants that show increased phosphotyrosine content, reflecting a change in molecular function.

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

Genes: 1956

Variants: A289V G598V L861Q T263P

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

Evidence Type(s): Oncogenic

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

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

Genes: 1956

Variants: A289V G598V L861Q R108K T263P

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

Evidence Type(s): Oncogenic

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

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

Genes: 1956

Variants: A289V G598V L861Q R108K T263P

[Paragraph-level] PMCID: PMC1702556 Section: RESULTS PassageIndex: 5

Evidence Type(s): Diagnostic

Summary: Evidence Type: Diagnostic | Mutation: R108K | Summary: The R108K mutation is associated with defining the presence of EGFR missense mutations in gliomas, indicating its role in classifying the disease. Evidence Type: Diagnostic | Mutation: T263P | Summary: The T263P mutation is part of the common amino acid changes in EGFR missense mutations, contributing to the classification of gliomas. Evidence Type: Diagnostic | Mutation: A289V | Summary: The A289V mutation is identified as one of the common amino acid changes in EGFR missense mutations, aiding in the diagnosis of gliomas. Evidence Type: Diagnostic | Mutation: G598V | Summary: The G598V mutation is included among the common amino acid changes in EGFR missense mutations, which helps in the diagnostic classification of gliomas.

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

Genes: 1956

Variants: A289V G598V R108K T263P

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

Evidence Type(s): Oncogenic

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

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

Genes: 1956

Variants: A289 A289D A289T E330K L861Q R108 R324L

[Paragraph-level] PMCID: PMC4385014 Section: ABSTRACT PassageIndex: 4

Evidence Type(s): Predictive

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

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

Genes: 1956

Variants: L858R T790M

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

Evidence Type(s): Oncogenic

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

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

Genes: 5290

Variants: p.Glu542Lys p.Glu545Lys p.His1047Arg

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

Evidence Type(s): Oncogenic

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

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

Genes: 5290

Variants: p.Glu453Lys p.Gly914Arg

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

Evidence Type(s): Oncogenic

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

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

Genes: 5290

Variants: p.Arg93Gln p.Cys378Tyr p.Gly106Val

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

Evidence Type(s): Diagnostic, Predisposing, Oncogenic

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

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

Genes: 5290

Variants: p.Glu726Lys

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

Evidence Type(s): Oncogenic, Functional

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

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

Genes: 5290 7249

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

[Paragraph-level] PMCID: PMC5019182 Section: RESULTS PassageIndex: 9

Evidence Type(s): Diagnostic

Summary: Evidence Type: Diagnostic | Mutation: p.Glu542Lys | Summary: The p.Glu542Lys mutation is associated with developmental pediatric disorders, indicating its role in defining or classifying a disease subtype. Evidence Type: Diagnostic | Mutation: p.Glu545Lys | Summary: The p.Glu545Lys mutation is frequently observed in pediatric disorders, supporting its use in defining or classifying a disease subtype. Evidence Type: Diagnostic | Mutation: p.His1047Arg | Summary: The p.His1047Arg mutation is highly recurrent in developmental pediatric disorders, suggesting its role in defining or classifying a disease subtype.

Gene→Variant (gene-first): 5290:p.Glu542Lys 5290:p.Glu545Lys 5290:p.Glu726Lys 5290:p.Gly914Arg 5290:p.His1047Arg

Genes: 5290

Variants: p.Glu542Lys p.Glu545Lys p.Glu726Lys p.Gly914Arg p.His1047Arg

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

Evidence Type(s): Oncogenic

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

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

Genes: 5290

Variants: p.Arg93Gln

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

Evidence Type(s): Oncogenic

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

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

Genes: 5290

Variants: p.Glu545Lys p.His1047Arg

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

Evidence Type(s): Predictive, Oncogenic

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

Gene→Variant (gene-first): 3815:V559D

Genes: 3815

Variants: V559D

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

Evidence Type(s): Oncogenic, Predictive

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

Gene→Variant (gene-first): 3815:V559D

Genes: 3815

Variants: V559D

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

Evidence Type(s): Predictive, Functional

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

Gene→Variant (gene-first): 3815:V559D

Genes: 3815

Variants: V559D

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

Evidence Type(s): Predictive, Oncogenic

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

Gene→Variant (gene-first): 3815:V559D

Genes: 3815

Variants: V559D

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

Evidence Type(s): Oncogenic, Functional

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

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

Genes: 3815

Variants: A829P L576P V559D

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

Evidence Type(s): Functional, Oncogenic

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

Gene→Variant (gene-first): 3815:V559D

Genes: 3815

Variants: V559D

[Paragraph-level] PMCID: PMC5762309 Section: RESULTS PassageIndex: 4

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: V559D | Summary: The V559D mutation alters the molecular function of the KIT protein, as indicated by its role in auto-phosphorylation in the context of the study.

Gene→Variant (gene-first): 3815:V559D

Genes: 3815

Variants: V559D

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

Evidence Type(s): Predictive

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

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

Genes: 3815

Variants: D816V L576P N822K T670I V559D V654A

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

Evidence Type(s): Functional, Oncogenic

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

Gene→Variant (gene-first): 3815:V559D

Genes: 3815

Variants: V559D

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

Evidence Type(s): Oncogenic, Functional

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

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

Genes: 6016

Variants: p.M90I

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

Evidence Type(s): Oncogenic

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

Gene→Variant (gene-first): 6016:Q40L

Genes: 6016

Variants: Q40L

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

Evidence Type(s): Oncogenic

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

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

Genes: 3845 1956 6016

Variants: G12V L858R Q40 Q40L Q79L

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

Evidence Type(s): Oncogenic

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

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

Genes: 6016

Variants: F82L M90I p.M90I

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

Evidence Type(s): Oncogenic

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

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

Genes: 6016

Variants: p.R122L

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

Evidence Type(s): Oncogenic, Predisposing

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

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

Genes: NA 6016

Variants: alanine 77 p.A77P p.A77S

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

Evidence Type(s): Oncogenic

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

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

Genes: 6016

Variants: p.M90I

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

Evidence Type(s): Oncogenic, Functional

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

Gene→Variant (gene-first): 672:E384X

Genes: 672

Variants: E384X

[Paragraph-level] PMCID: PMC3923676 Section: RESULTS PassageIndex: 6

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: G C | Summary: The G C missense mutations in the DNAH5 gene are noted to alter the molecular function of the dynein protein, which is part of the microtubule-associated motor protein complex.

Gene→Variant (gene-first): 1767:G C

Genes: 1767

Variants: G C

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

Evidence Type(s): Oncogenic

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

Gene→Variant (gene-first): 672:E384X

Genes: 672

Variants: E384X

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

Evidence Type(s): Oncogenic, Predictive

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

Gene→Variant (gene-first): 672:E384X

Genes: 672

Variants: E384X

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

Evidence Type(s): Predictive, Oncogenic

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

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

Genes: 2064 1956

Variants: D769H D769Y I767M K753I L755S R678Q S310F S310Y V842I

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

Evidence Type(s): Oncogenic, Diagnostic, Prognostic

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

Gene→Variant (gene-first): 90:K27M

Genes: 90

Variants: K27M

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

Evidence Type(s): Oncogenic, Functional

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

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

Genes: 4486 5395 7297

Variants: A35V C192Y R1027H

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

Evidence Type(s): Oncogenic

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

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

Genes: 80312

Variants: H1297Y

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

Evidence Type(s): Oncogenic

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

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

Genes: 3718

Variants: A572 A572T A572V M511I

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

Evidence Type(s): Predictive, Oncogenic

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

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

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

Evidence Type(s): Predictive, Prognostic, Oncogenic

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

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paragraph-level] PMCID: PMC8078423 Section: ABSTRACT PassageIndex: 2

Evidence Type(s): Predictive, Prognostic

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

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

Genes: 673

Variants: BRAFV600E

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

Evidence Type(s): Predictive, Oncogenic

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

Gene→Variant (gene-first): 1956:T790M

Genes: 1956

Variants: T790M

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

Evidence Type(s): Predictive, Oncogenic

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

Gene→Variant (gene-first): 1956:T790M

Genes: 1956

Variants: T790M

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

Evidence Type(s): Predictive, Diagnostic

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

Gene→Variant (gene-first): 1956:T790M

Genes: 1956

Variants: T790M

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

Evidence Type(s): Predictive, Oncogenic

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

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

Genes: 673

Variants: V600E p.T599dup p.V600E

[Paragraph-level] PMCID: PMC2766370 Section: RESULTS PassageIndex: 10

Evidence Type(s): None

Summary: Not enough information in this passage.

Gene→Variant (gene-first): 1956:c.2192G>A 1956:c.2224G>A 1956:c.2488G>A

Genes: 1956

Variants: c.2192G>A c.2224G>A c.2488G>A

[Paragraph-level] PMCID: PMC2766370 Section: RESULTS PassageIndex: 9

Evidence Type(s): None

Summary: Not enough information in this passage.

Gene→Variant (gene-first): 3845:C>A 3845:C>T 3845:G>A 7157:c.100C>T 1956:c.22G>A 3845:c.32C>A 3845:c.38 (codon 13) 3845:c.38G>A 7157:c.59C>T

Genes: 3845 7157 1956

Variants: C>A C>T G>A c.100C>T c.22G>A c.32C>A c.38 (codon 13) c.38G>A c.59C>T

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

Evidence Type(s): Oncogenic, Functional

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

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

Genes: 3845

Variants: c.34G>T p.G12C

[Paragraph-level] PMCID: PMC2766370 Section: RESULTS PassageIndex: 6

Evidence Type(s): None

Summary: Not enough information in this passage.

Gene→Variant (gene-first): 3845:c.38G>A 3845:delE746_A750 EGFR

Genes: 3845

Variants: c.38G>A delE746_A750 EGFR

[Paragraph-level] PMCID: PMC2766370 Section: RESULTS PassageIndex: 3

Evidence Type(s): None

Summary: Not enough information in this passage.

Gene→Variant (gene-first): 3845:c.38G>A

Genes: 3845

Variants: c.38G>A

[Paragraph-level] PMCID: PMC8008494 Section: RESULTS PassageIndex: 9

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: c.8723T>G | Summary: The variant c.8723T>G (p.Val2908Gly) was evaluated in a functional study and demonstrated sensitivity to multiple drugs, indicating an alteration in molecular function. Evidence Type: Functional | Mutation: c.8905G>A | Summary: The variant c.8905G>A (p.Val2969Met) was also assessed in a functional study and showed consistent sensitivity to various drugs, reflecting a change in molecular function.

Gene→Variant (gene-first): 675:c.8723T>G 675:c.8905G>A 675:p.Val2908Gly 675:p.Val2969Met

Genes: 675

Variants: c.8723T>G c.8905G>A p.Val2908Gly p.Val2969Met

[Paragraph-level] PMCID: PMC8008494 Section: RESULTS PassageIndex: 3

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: 2619 from Trp to Gly | Summary: Variants that change residue 2619 from Trp to Gly, Ser, or Cys all resulted in loss of function, indicating a critical role for this residue in molecular function. Evidence Type: Functional | Mutation: 2723 from Asp to Asn | Summary: Variants that change residue 2723 from Asp to Asn, His, Tyr, Ala, Gly, and Val consistently resulted in loss of function, suggesting a negatively charged amino acid is required at this position. Evidence Type: Functional | Mutation: Leu3180 | Summary: Differential effects on function were observed for two alterations in residue Leu3180, where a Pro substitution resulted in loss of function but an Arg substitution resulted in a functional protein. Evidence Type: Functional | Mutation: p.Gly2508Ser | Summary: The variant p.Gly2508Ser is associated with loss of function, indicating its critical role in the molecular function of the protein. Evidence Type: Functional | Mutation: p.Gly2508Arg | Summary: The variant p.Gly2508Arg is associated with loss of function, indicating its critical role in the molecular function of the protein. Evidence Type: Functional | Mutation: p.Ala2603Ser | Summary: The variant p.Ala2603Ser is associated with loss of function, indicating its critical role in the molecular function of the protein. Evidence Type: Functional | Mutation: p.Arg2625Lys | Summary: The variant p.Arg2625Lys is associated with loss of function, indicating its critical role in the molecular function of the protein. Evidence Type: Functional | Mutation: p.Ile2627Val | Summary: The variant p.Ile2627Val is associated with loss of function, indicating its critical role in the molecular function of the protein. Evidence Type: Functional | Mutation: p.Asn3124His | Summary: The variant p.Asn3124His is associated with loss of function, indicating its critical role in the molecular function of the protein.

Gene→Variant (gene-first): NA:2619 from Trp to Gly 675:2723 from Asp to Asn 353:7522G>A 353:7807G>T 353:7874G>A 353:7879A>G NA:Leu3180 353:Phe/Asn 353:c.7522G>C 675:c.7880T>A 675:c.9370A>C 675:c.9371A>T 675:c.9539T>C 675:p.Ala2603Ser 675:p.Arg2625Lys 675:p.Asn3124His 353:p.Gly2508Arg 675:p.Gly2508Ser 675:p.Ile2627Val

Genes: NA 675 353

Variants: 2619 from Trp to Gly 2723 from Asp to Asn 7522G>A 7807G>T 7874G>A 7879A>G Leu3180 Phe/Asn c.7522G>C c.7880T>A c.9370A>C c.9371A>T c.9539T>C p.Ala2603Ser p.Arg2625Lys p.Asn3124His p.Gly2508Arg p.Gly2508Ser p.Ile2627Val

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

Evidence Type(s): Predictive

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

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

Genes: 238

Variants: G1202R L1196M L1198F

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

Evidence Type(s): Predictive

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

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

Genes: 238

Variants: G1202R L1196M L1198F

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

Evidence Type(s): Predictive, Oncogenic

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

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

Genes: 238

Variants: G1202R L1196M L1198 L1198F

[Paragraph-level] PMCID: PMC9398166 Section: RESULTS PassageIndex: 8

Evidence Type(s): Predictive

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

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

Genes: 238

Variants: G1202R G1269A L1204V

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

Evidence Type(s): Oncogenic, Functional

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

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

Genes: 238

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

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

Evidence Type(s): Predictive

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

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

Genes: 238

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

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

Evidence Type(s): Predictive, Oncogenic

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

Gene→Variant (gene-first): 238:G1202

Genes: 238

Variants: G1202

[Paragraph-level] PMCID: PMC6791388 Section: RESULTS PassageIndex: 14

Evidence Type(s): Functional, Predictive

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

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

Genes: 7157

Variants: S133 Ser133 Serine 133

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

Evidence Type(s): Predictive, Functional, Oncogenic

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

Gene→Variant (gene-first): 596:G101V

Genes: 596

Variants: G101V

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

Evidence Type(s): Predictive, Functional

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

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

Genes: 596

Variants: E152 E152A G101V V101

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

Evidence Type(s): Predictive, Oncogenic

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

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

Genes: 2064

Variants: p.L755P

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

Evidence Type(s): Predictive, Oncogenic

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

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

Genes: 2064

Variants: p.L755P

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

Evidence Type(s): Predictive, Oncogenic

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

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

Genes: 2064

Variants: p.L755P

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

Evidence Type(s): Predictive, Oncogenic

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

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

Genes: 2064

Variants: c.2262_2264delinsTCC p.(L755P)

[Paragraph-level] PMCID: PMC8881279 Section: ABSTRACT PassageIndex: 6

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: E401G | Summary: The ERBB2 E401G variant alters molecular function by enhancing C-terminal phosphorylation and maintaining the stability of the EGFR-HER2 heterodimer. Evidence Type: Functional | Mutation: S310F | Summary: The ERBB2 S310F variant also alters molecular function by enhancing C-terminal phosphorylation and maintaining the stability of the EGFR-HER2 heterodimer.

Gene→Variant (gene-first): 2176:E401G 2064:S310F

Genes: 2176 2064

Variants: E401G S310F

[Paragraph-level] PMCID: PMC8881279 Section: ABSTRACT PassageIndex: 4

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: E401G | Summary: The E401G variant was analyzed for its biological effects and mechanisms through molecular dynamics simulation, indicating an alteration in molecular function. Evidence Type: Oncogenic | Mutation: E401G | Summary: The E401G variant is described as an activating mutation, suggesting its contribution to tumor development or progression. Evidence Type: Functional | Mutation: S310F | Summary: The S310F variant was included in the analysis of ERBB2 expression vectors, indicating an alteration in molecular function. Evidence Type: Oncogenic | Mutation: S310F | Summary: The S310F variant is known to be an activating mutation, suggesting its role in tumor development or progression. Evidence Type: Functional | Mutation: E321G | Summary: The E321G variant was part of the ERBB2 expression vectors analysis, indicating an alteration in molecular function. Evidence Type: Oncogenic | Mutation: E321G | Summary: The E321G variant is classified as an activating mutation, suggesting its contribution to tumor development or progression.

Gene→Variant (gene-first): 7157:E321G 2176:E401G 2064:S310F

Genes: 7157 2176 2064

Variants: E321G E401G S310F

[Paragraph-level] PMCID: PMC8881279 Section: ABSTRACT PassageIndex: 2

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: 1157A > G | Summary: The variant 1157A > G (E401G) is associated with efforts to clarify its biological functions and mechanisms of activation, indicating a focus on its molecular function.

Gene→Variant (gene-first): 4609:1157A > G 2176:E401G

Genes: 4609 2176

Variants: 1157A > G E401G

[Paragraph-level] PMCID: PMC8881279 Section: RESULTS PassageIndex: 17

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: E401G | Summary: The E401G mutation in ERBB2 is associated with increased tumor growth in vivo, indicating its role in tumor development or progression. Evidence Type: Functional | Mutation: E401G | Summary: The E401G mutation alters the molecular function of ERBB2, contributing to enhanced tumor-forming capacity.

Gene→Variant (gene-first): 2176:E401G

Genes: 2176

Variants: E401G

[Paragraph-level] PMCID: PMC8881279 Section: RESULTS PassageIndex: 16

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: E401G | Summary: The variant ERBB2 E401G alters the proliferative and invasive capacities of cancer cells, indicating a change in molecular function. Evidence Type: Functional | Mutation: S310F | Summary: The variant ERBB2 S310F is associated with a significantly higher proliferation rate in cancer cells, suggesting an alteration in molecular function.

Gene→Variant (gene-first): 2176:E401G 2064:S310F

Genes: 2176 2064

Variants: E401G S310F

[Paragraph-level] PMCID: PMC8881279 Section: RESULTS PassageIndex: 15

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: E401G | Summary: The passage suggests that the ERBB2 E401G variant has biological effects, indicating that it alters molecular or biochemical function.

Gene→Variant (gene-first): 2176:E401G

Genes: 2176

Variants: E401G

[Paragraph-level] PMCID: PMC8881279 Section: RESULTS PassageIndex: 14

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: E401G | Summary: The E401G mutation alters molecular signaling activity by activating the MAPK pathway, as evidenced by elevated phosphorylation of ERK in cells expressing this variant. Evidence Type: Functional | Mutation: S310F | Summary: The S310F mutation also alters molecular signaling activity by activating the MAPK pathway, demonstrated by increased phosphorylation of ERK in cells expressing this variant.

Gene→Variant (gene-first): 2176:E401G 2064:S310F

Genes: 2176 2064

Variants: E401G S310F

[Paragraph-level] PMCID: PMC8881279 Section: RESULTS PassageIndex: 12

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: E401G | Summary: The E401G mutation appears to stabilize the dimer interface of the HER2-EGFR complex, indicating an alteration in molecular function. Evidence Type: Functional | Mutation: S310F | Summary: The S310F mutation also seems to stabilize the dimer interface of the HER2-EGFR complex, suggesting a change in molecular function.

Gene→Variant (gene-first): 2176:E401G 2064:S310F

Genes: 2176 2064

Variants: E401G S310F

[Paragraph-level] PMCID: PMC8881279 Section: RESULTS PassageIndex: 11

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: E401G | Summary: The E401G mutation is analyzed in the context of HER-family dimers, suggesting it alters the molecular interactions and stability of these complexes. Evidence Type: Functional | Mutation: S310F | Summary: The S310F mutation is examined for its role in the formation and stability of HER-family dimers, indicating a potential alteration in molecular function.

Gene→Variant (gene-first): 2176:E401G 2064:S310F

Genes: 2176 2064

Variants: E401G S310F

[Paragraph-level] PMCID: PMC8881279 Section: RESULTS PassageIndex: 10

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: p.(E401G) | Summary: The mutation p.(E401G) alters the molecular function by stabilizing the ligand-free EGFR HER2 heterodimer.

Gene→Variant (gene-first): 2176:p.(E401G)

Genes: 2176

Variants: p.(E401G)

[Paragraph-level] PMCID: PMC8881279 Section: RESULTS PassageIndex: 9

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: E401G | Summary: The HER2 E401G mutation is associated with increased phosphorylation levels of HER2 and EGFR, suggesting its role in tumor development or progression. Evidence Type: Oncogenic | Mutation: S310F | Summary: The HER2 S310F mutation is linked to increased phosphorylation levels of HER2 and EGFR, indicating its contribution to tumor development or progression.

Gene→Variant (gene-first): 2176:E401G 2064:S310F

Genes: 2176 2064

Variants: E401G S310F

[Paragraph-level] PMCID: PMC8881279 Section: RESULTS PassageIndex: 8

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: E401G | Summary: The E401G mutation is associated with the identification of potential dimerization partners of the HER2 protein, indicating an alteration in molecular function.

Gene→Variant (gene-first): 2176:E401G

Genes: 2176

Variants: E401G

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

Evidence Type(s): Predictive, Functional

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

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

Genes: 1956

Variants: L858R N771insSVD

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

Evidence Type(s): Predisposing, Oncogenic, Functional

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

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

Genes: 3091

Variants: c.236A>G p.Tyr79Cys

[Paragraph-level] PMCID: PMC4234187 Section: RESULTS PassageIndex: 16

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: C118S | Summary: The KrasC118S mutation is implicated in oncogenic behavior, particularly in the context of the KrasG13D background, suggesting its contribution to tumor development. Evidence Type: Oncogenic | Mutation: G13D | Summary: The KrasG13D mutation is described as an oncogenic mutant, indicating its role in tumor progression. Evidence Type: Functional | Mutation: C118S | Summary: The C118S mutation alters the signaling and transformation properties of Kras, as evidenced by changes in P-Erk1/2 levels upon EGF treatment. Evidence Type: Functional | Mutation: G13D | Summary: The G13D mutation, when combined with C118S, affects the molecular function of Kras, influencing signaling pathways related to oncogenic activity.

Gene→Variant (gene-first): 4843:C118 4843:C118S 3845:G13D 4893:Q61L

Genes: 4843 3845 4893

Variants: C118 C118S G13D Q61L

[Paragraph-level] PMCID: PMC4234187 Section: RESULTS PassageIndex: 15

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: C118S | Summary: The C118S mutation in the Kras allele is associated with oncogenic behavior, as it was tested in Kras+/C118S mice and analyzed for its role in tumor development. Evidence Type: Oncogenic | Mutation: Q61R | Summary: The Q61R mutation in the native Kras allele is identified as oncogenic, contributing to tumor development in the analyzed lung tumors from Kras+/C118S mice. Evidence Type: Oncogenic | Mutation: Q61R/L | Summary: The Q61R/L mutation is classified as oncogenic, as it was detected in the native Kras allele and is implicated in tumor progression in the studied samples.

Gene→Variant (gene-first): 4843:C118S 4893:Q61R 3845:Q61R/L

Genes: 4843 4893 3845

Variants: C118S Q61R Q61R/L

[Paragraph-level] PMCID: PMC4234187 Section: RESULTS PassageIndex: 13

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: C118S | Summary: The KrasC118S allele is described as having a negative effect on lung tumorigenesis, suggesting it may suppress the tumorigenic activity of the oncogenic Kras allele. Evidence Type: Oncogenic | Mutation: G12D | Summary: The KrasG12D allele is established to promote tumorigenesis, indicating its role as an oncogenic mutation in lung cancer development.

Gene→Variant (gene-first): 4843:C118S 3845:G12D

Genes: 4843 3845

Variants: C118S G12D

[Paragraph-level] PMCID: PMC4234187 Section: RESULTS PassageIndex: 12

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: G12D | Summary: The G12D mutation is associated with tumor development as indicated by its presence in the KrasLSL-G12D/+ and KrasLSL-G12D/C118S mice models. Evidence Type: Oncogenic | Mutation: C118S | Summary: The C118S mutation contributes to tumor development, as evidenced by its presence in the KrasLSL-G12D/C118S mouse model alongside the G12D mutation.

Gene→Variant (gene-first): 4843:C118S 3845:G12D

Genes: 4843 3845

Variants: C118S G12D

[Paragraph-level] PMCID: PMC4234187 Section: RESULTS PassageIndex: 11

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: C118S | Summary: The C118S mutation in Kras is associated with tumor progression and is implicated in the development of mixed solid/papillary adenomas, indicating its role in tumor development. Evidence Type: Functional | Mutation: C118S | Summary: The C118S mutation appears to alter the molecular function of Ras signaling, as evidenced by the reduced P-Akt levels in the Kras+/C118S cohort compared to other genotypes.

Gene→Variant (gene-first): 4843:C118S

Genes: 4843

Variants: C118S

[Paragraph-level] PMCID: PMC4234187 Section: RESULTS PassageIndex: 10

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: C118S | Summary: The KrasC118S allele is associated with a reduction in tumor burden and a shift towards smaller tumors in mice, indicating its role in tumor development and progression. Evidence Type: Functional | Mutation: C118S | Summary: The presence of the KrasC118S allele alters the tumor size and incidence of adenomas, suggesting a change in molecular or biochemical function related to carcinogenesis.

Gene→Variant (gene-first): 4843:C118S

Genes: 4843

Variants: C118S

[Paragraph-level] PMCID: PMC4234187 Section: RESULTS PassageIndex: 9

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: C118S | Summary: The KrasC118S mutation is implicated in tumor development as it is assessed in the context of lung tumors induced by the carcinogen urethane. Evidence Type: Oncogenic | Mutation: Q61R/L | Summary: The Q61R/L mutations in Kras are characterized as oncogenic, contributing to tumor development in the context of urethane-induced lung tumors.

Gene→Variant (gene-first): 4843:C118S 3845:Q61R/L

Genes: 4843 3845

Variants: C118S Q61R/L

[Paragraph-level] PMCID: PMC4234187 Section: RESULTS PassageIndex: 7

Evidence Type(s): None

Summary: Not enough information in this passage.

Gene→Variant (gene-first): 4843:C118S

Genes: 4843

Variants: C118S

[Paragraph-level] PMCID: PMC4234187 Section: RESULTS PassageIndex: 6

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: C118S | Summary: The C118S mutation is mentioned in the context of KrasC118S/C118S mice appearing normal, suggesting that this variant may alter molecular or biochemical function, although the specific functional impact is not detailed.

Gene→Variant (gene-first): 4843:C118S

Genes: 4843

Variants: C118S

[Paragraph-level] PMCID: PMC4234187 Section: RESULTS PassageIndex: 5

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: C118S | Summary: The C118S mutation in the Kras gene is associated with tumorigenesis, as it is involved in the sensitivity of tumor initiation to Ras protein levels. Evidence Type: Functional | Mutation: C118S | Summary: The C118S mutation affects the ability of eNOS to stimulate the MAPK pathway, indicating a change in molecular function. Evidence Type: Functional | Mutation: S1177D | Summary: The S1177D mutation in eNOS alters the levels of phosphorylated Erk1/2, demonstrating a change in biochemical function.

Gene→Variant (gene-first): 4843:C118S 4843:G353>C 4846:S1177D

Genes: 4843 4846

Variants: C118S G353>C S1177D

[Paragraph-level] PMCID: PMC4234187 Section: RESULTS PassageIndex: 3

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: C118S | Summary: The C118S mutation alters the redox-dependent reactions at this site, specifically blocking Ras activation, indicating a change in molecular function. Evidence Type: Oncogenic | Mutation: C118S | Summary: The C118S mutation in the Kras gene is implicated in tumorigenesis, contributing to tumor development or progression. Evidence Type: Functional | Mutation: G353>C | Summary: The G353>C transversion results in the C118S mutation, which affects the molecular function of Ras by blocking activation. Evidence Type: Oncogenic | Mutation: G353>C | Summary: The G353>C transversion is associated with the C118S mutation in Kras, which is known to contribute to tumorigenesis.

Gene→Variant (gene-first): 4843:C118 4843:C118S 4843:G353 transversion to C 4843:G353>C

Genes: 4843

Variants: C118 C118S G353 transversion to C G353>C

[Paragraph-level] PMCID: PMC2970593 Section: RESULTS PassageIndex: 5

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: W731 | Summary: The W731 mutation alters molecular function as it is located in the TK domain critical for EGFR activity. Evidence Type: Functional | Mutation: E734 | Summary: The E734 mutation alters molecular function as it is located in the TK domain critical for EGFR activity. Evidence Type: Functional | Mutation: T785 | Summary: The T785 mutation alters molecular function as it is located in the TK domain critical for EGFR activity. Evidence Type: Functional | Mutation: C797 | Summary: The C797 mutation alters molecular function as it is located in the TK domain critical for EGFR activity. Evidence Type: Functional | Mutation: Y801 | Summary: The Y801 mutation alters molecular function as it is located in the TK domain critical for EGFR activity. Evidence Type: Functional | Mutation: R831 | Summary: The R831 mutation alters molecular function as it is located in the TK domain critical for EGFR activity. Evidence Type: Functional | Mutation: L858 | Summary: The L858 mutation alters molecular function as it is located in the TK domain critical for EGFR activity. Evidence Type: Functional | Mutation: E868 | Summary: The E868 mutation alters molecular function as it is located in the TK domain critical for EGFR activity.

Gene→Variant (gene-first): 1956:C797 NA:E734 NA:T785 1956:E868 1956:L858 1956:R831 NA:W731 1956:Y801

Genes: 1956 NA

Variants: C797 E734 T785 E868 L858 R831 W731 Y801

[Paragraph-level] PMCID: PMC2970593 Section: RESULTS PassageIndex: 3

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: C797Y | Summary: The C797Y mutation is identified as a somatic variant in the tyrosine kinase domain of EGFR, contributing to tumor development. Evidence Type: Oncogenic | Mutation: E734Q | Summary: The E734Q mutation is identified as a somatic variant in the tyrosine kinase domain of EGFR, contributing to tumor development. Evidence Type: Oncogenic | Mutation: E868G | Summary: The E868G mutation is identified as a somatic variant in the tyrosine kinase domain of EGFR, contributing to tumor development. Evidence Type: Oncogenic | Mutation: L831H | Summary: The L831H mutation is identified as a somatic variant in the tyrosine kinase domain of EGFR, contributing to tumor development. Evidence Type: Oncogenic | Mutation: L858R | Summary: The L858R mutation is identified as a somatic variant in the tyrosine kinase domain of EGFR, contributing to tumor development and increasing sensitivity to the EGFR inhibitor Erlotinib. Evidence Type: Oncogenic | Mutation: T785A | Summary: The T785A mutation is identified as a somatic variant in the tyrosine kinase domain of EGFR, contributing to tumor development. Evidence Type: Oncogenic | Mutation: W731L | Summary: The W731L mutation is identified as a somatic variant in the tyrosine kinase domain of EGFR, contributing to tumor development. Evidence Type: Oncogenic | Mutation: Y801H | Summary: The Y801H mutation is identified as a somatic variant in the tyrosine kinase domain of EGFR, contributing to tumor development.

Gene→Variant (gene-first): 1956:C797Y 1956:E734Q 1956:E868G 1956:L831H 1956:L858R 1956:T785A 1956:W731L 1956:Y801H

Genes: 1956

Variants: C797Y E734Q E868G L831H L858R T785A W731L Y801H

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

Evidence Type(s): Predictive, Oncogenic

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

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

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC7612475 Section: RESULTS PassageIndex: 17

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: K700E | Summary: The SF3B1 K700E mutation is associated with a BRCA-like phenotype, contributing to tumor development by compromising replication fork stability and exhibiting cellular deficits characteristic of BRCA1/2 loss. Evidence Type: Functional | Mutation: K700E | Summary: The K700E mutation alters the molecular function of SF3B1, leading to increased fork degradation and failure to recruit Rad51 to stalled replication forks.

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

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC7612475 Section: RESULTS PassageIndex: 14

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: K700E | Summary: The SF3B1K700E mutation alters the efficiency of replication fork restart following a transient replication block, indicating a change in molecular function related to DNA replication dynamics.

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

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC7612475 Section: RESULTS PassageIndex: 13

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: D210N | Summary: The D210N substitution in RNaseH1 alters its ability to resolve R-loops, leading to their accumulation, which is assessed through fluorescence microscopy. Evidence Type: Oncogenic | Mutation: D210N | Summary: The D210N mutation contributes to the accumulation of R-loops, which can lead to increased genome instability, a factor associated with tumor development.

Gene→Variant (gene-first): 246243:D210N

Genes: 246243

Variants: D210N

[Paragraph-level] PMCID: PMC7612475 Section: RESULTS PassageIndex: 12

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: K700E | Summary: The SF3B1 K700E mutation alters molecular function by inducing unscheduled R-loops and stalled replication forks, impacting replication fork protection and restart.

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

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC7612475 Section: RESULTS PassageIndex: 9

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: K700E | Summary: The SF3B1K700E mutation alters the molecular function of homologous recombination (HR) by affecting the resolution of Rad51 foci and decreasing sister chromatid exchanges, indicating a defect in HR repair processes. Evidence Type: Oncogenic | Mutation: K700E | Summary: The SF3B1K700E mutation contributes to tumor development or progression by impairing the repair of DNA double-strand breaks, which is critical for maintaining genomic stability.

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

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC7612475 Section: RESULTS PassageIndex: 8

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: K700E | Summary: The SF3B1K700E mutation alters the molecular function related to DNA repair, as evidenced by impaired homologous recombination (HR) and increased basal DNA damage in cells expressing this mutation. Evidence Type: Oncogenic | Mutation: K700E | Summary: The SF3B1K700E mutation contributes to tumor development or progression, as indicated by its association with defects in double-strand break (DSB) repair and its presence in cancer-derived cell lines.

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

Genes: 23451

Variants: K700E

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

Evidence Type(s): Predictive, Functional, Oncogenic

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

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

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC3184204 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Predisposing, Functional

Summary: Evidence Type: Predisposing | Mutation: c.1061C>T | Summary: The c.1061C>T mutation is identified as a heterozygous variant in the GATA2 gene that segregates with the multigenerational transmission of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), indicating its role as a predisposition gene. Evidence Type: Predisposing | Mutation: c.1063_1065delACA | Summary: The c.1063_1065delACA mutation is reported in a family with MDS/AML, supporting its classification as a predisposing variant associated with familial forms of the disease. Evidence Type: Functional | Mutation: c.1061C>T | Summary: The c.1061C>T mutation alters the molecular function of the GATA2 transcription factor, affecting transactivation of target genes, cellular differentiation, apoptosis, and global gene expression. Evidence Type: Functional | Mutation: c.1063_1065delACA | Summary: The c.1063_1065delACA mutation also impacts the molecular function of GATA2, influencing its role in transactivation and other cellular processes.

Gene→Variant (gene-first): 2624:c.1061C>T 2624:c.1063_1065delACA 2624:p.Thr354Met 6688:p.Thr355del

Genes: 2624 6688

Variants: c.1061C>T c.1063_1065delACA p.Thr354Met p.Thr355del

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

Evidence Type(s): Predictive, Prognostic

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

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

Genes: 2322

Variants: D835Y F691

[Paragraph-level] PMCID: PMC7190743 Section: RESULTS PassageIndex: 25

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: P354Q | Summary: The variant P354Q is classified as Pathogenic, indicating it contributes to tumor development or progression. Evidence Type: Oncogenic | Mutation: T202I | Summary: The variant T202I is classified as Pathogenic, indicating it contributes to tumor development or progression. Evidence Type: Oncogenic | Mutation: T78A | Summary: The variant T78A is classified as Pathogenic, indicating it contributes to tumor development or progression. Evidence Type: Oncogenic | Mutation: I135V | Summary: The variant I135V is classified as Likely Pathogenic, indicating it contributes to tumor development or progression. Evidence Type: Oncogenic | Mutation: N340H | Summary: The variant N340H is classified as Likely Pathogenic, indicating it contributes to tumor development or progression. Evidence Type: Oncogenic | Mutation: N356D | Summary: The variant N356D is classified as Likely Pathogenic, indicating it contributes to tumor development or progression. Evidence Type: Oncogenic | Mutation: K402N | Summary: The variant K402N is classified as Likely Pathogenic, indicating it contributes to tumor development or progression. Evidence Type: Oncogenic | Mutation: N117S | Summary: The variant N117S is classified as Likely Pathogenic, indicating it contributes to tumor development or progression. Evidence Type: Oncogenic | Mutation: Y180H | Summary: The variant Y180H is classified as Likely Pathogenic, indicating it contributes to tumor development or progression. Evidence Type: Oncogenic | Mutation: I203V | Summary: The variant I203V is classified as Likely Pathogenic, indicating it contributes to tumor development or progression. Evidence Type: Oncogenic | Mutation: Q298E | Summary: The variant Q298E is classified as Likely Pathogenic, indicating it contributes to tumor development or progression. Evidence Type: Oncogenic | Mutation: N340D | Summary: The variant N340D is classified as Likely Pathogenic, indicating it contributes to tumor development or progression. Evidence Type: Oncogenic | Mutation: K342N | Summary: The variant K342N is classified as Likely Pathogenic, indicating it contributes to tumor development or progression. Evidence Type: Oncogenic | Mutation: L345V | Summary: The variant L345V is classified as Likely Pathogenic, indicating it contributes to tumor development or progression. Evidence Type: Oncogenic | Mutation: I400V | Summary: The variant I400V is classified as Likely Pathogenic, indicating it contributes to tumor development or progression.

Gene→Variant (gene-first): 5728:A79T 5728:C211W 5728:E157G 5728:H123Q 5728:I135V 5728:I203V 5728:I400V 5728:K342N 5728:K402N 5728:L345V 5728:L70V 5728:M35V 5728:N117S 5728:N228S 5728:N340D 5728:N340H 5728:N356D 5728:P354Q 5728:Q298E 5728:S229T 5728:T202I 5728:T78A 5728:W274L 5728:Y176C 5728:Y180H 5728:Y65C

Genes: 5728

Variants: A79T C211W E157G H123Q I135V I203V I400V K342N K402N L345V L70V M35V N117S N228S N340D N340H N356D P354Q Q298E S229T T202I T78A W274L Y176C Y180H Y65C

[Paragraph-level] PMCID: PMC7190743 Section: RESULTS PassageIndex: 16

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: A126D | Summary: The A126D variant alters molecular function by exhibiting a change in stability between parental and PTEN-KO cells, suggesting its interaction with endogenous PTEN has minimal influence. Evidence Type: Functional | Mutation: A126P | Summary: The A126P variant alters molecular function by exhibiting a change in stability between parental and PTEN-KO cells, indicating its interaction with endogenous PTEN has minimal influence. Evidence Type: Functional | Mutation: H123Q | Summary: The H123Q variant alters molecular function by exhibiting a change in stability between parental and PTEN-KO cells, suggesting its interaction with endogenous PTEN has minimal influence. Evidence Type: Functional | Mutation: P38H | Summary: The P38H variant alters molecular function by exhibiting a change in stability between parental and PTEN-KO cells, indicating its interaction with endogenous PTEN has minimal influence. Evidence Type: Functional | Mutation: R130L | Summary: The R130L variant alters molecular function by exhibiting a change in stability between parental and PTEN-KO cells, suggesting its interaction with endogenous PTEN has minimal influence. Evidence Type: Functional | Mutation: R130Q | Summary: The R130Q variant alters molecular function by exhibiting a change in stability between parental and PTEN-KO cells, indicating its interaction with endogenous PTEN has minimal influence. Evidence Type: Functional | Mutation: C124S | Summary: The C124S variant alters molecular function by raising pAKT/AKT levels, consistent with a dominant negative phenotype. Evidence Type: Functional | Mutation: G129E | Summary: The G129E variant alters molecular function by raising pAKT/AKT levels, consistent with a dominant negative phenotype.

Gene→Variant (gene-first): 5728:A126D 5728:A126P 5728:C124S 5728:G129E 5728:H123Q 5728:P354Q 5728:P38H 5728:Q396R 5728:R130L 5728:R130Q

Genes: 5728

Variants: A126D A126P C124S G129E H123Q P354Q P38H Q396R R130L R130Q

[Paragraph-level] PMCID: PMC7190743 Section: RESULTS PassageIndex: 14

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: H93Y | Summary: The H93Y variant is associated with altered molecular function, specifically reduced protein stability compared to wild-type PTEN. Evidence Type: Functional | Mutation: P354Q | Summary: The P354Q variant does not show significant differences in protein stability compared to wild-type PTEN, indicating it may not alter molecular function. Evidence Type: Functional | Mutation: R130L | Summary: The R130L variant does not show significant differences in protein stability compared to wild-type PTEN, indicating it may not alter molecular function. Evidence Type: Functional | Mutation: R14G | Summary: The R14G variant does not show significant differences in protein stability compared to wild-type PTEN, indicating it may not alter molecular function. Evidence Type: Functional | Mutation: R15S | Summary: The R15S variant does not show significant differences in protein stability compared to wild-type PTEN, indicating it may not alter molecular function. Evidence Type: Functional | Mutation: T78A | Summary: The T78A variant does not show significant differences in protein stability compared to wild-type PTEN, indicating it may not alter molecular function.

Gene→Variant (gene-first): 5728:H93Y 5728:P354Q 5728:R130L 5728:R14G 5728:R15S 5728:T78A

Genes: 5728

Variants: H93Y P354Q R130L R14G R15S T78A

[Paragraph-level] PMCID: PMC7190743 Section: RESULTS PassageIndex: 12

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: A79T | Summary: The A79T variant retained wild-type-like function in the context of chemotaxis assays in C. elegans. Evidence Type: Functional | Mutation: C124S | Summary: The C124S variant exhibited complete loss of function (LoF) in the chemotaxis assays conducted in daf-18 mutant worms. Evidence Type: Functional | Mutation: D268E | Summary: The D268E variant showed partial loss of function (LoF) in the chemotaxis assays in daf-18 mutant worms. Evidence Type: Functional | Mutation: G132D | Summary: The G132D variant exhibited stronger negative chemotaxis than daf-18 mutants, indicating a functional alteration. Evidence Type: Functional | Mutation: P354Q | Summary: The P354Q variant retained wild-type-like function in the context of chemotaxis assays in C. elegans. Evidence Type: Functional | Mutation: T167N | Summary: The T167N variant showed partial loss of function (LoF) in the chemotaxis assays in daf-18 mutant worms. Evidence Type: Functional | Mutation: Y176C | Summary: The Y176C variant showed partial loss of function (LoF) in the chemotaxis assays in daf-18 mutant worms.

Gene→Variant (gene-first): 5728:A79T 5728:C124S 5728:D268E 5728:G132D 5728:P354Q 5728:T167N 5728:Y176C

Genes: 5728

Variants: A79T C124S D268E G132D P354Q T167N Y176C

[Paragraph-level] PMCID: PMC7190743 Section: RESULTS PassageIndex: 10

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: A79T | Summary: The A79T variant exhibited a gain-of-function (GoF) phenotype in axonal growth and altered PSD95 density and dendrite length, indicating a change in molecular function. Evidence Type: Functional | Mutation: C124S | Summary: The C124S variant showed complete loss of function (LoF) indistinguishable from GFP controls in terms of PSD95 density, indicating an alteration in molecular function. Evidence Type: Functional | Mutation: I101T | Summary: The I101T variant, along with C124S, increased soma size more than GFP, suggesting a change in molecular function related to neuronal growth. Evidence Type: Functional | Mutation: G132D | Summary: The G132D variant also increased soma size more than GFP, indicating an alteration in molecular function associated with neuronal growth. Evidence Type: Functional | Mutation: D268E | Summary: The D268E variant appeared wild-type-like in all measures of growth and synaptogenesis, suggesting it does not alter molecular function significantly.

Gene→Variant (gene-first): 5728:A79T 5728:C124S 5728:D268E 5728:G132D 5728:I101T

Genes: 5728

Variants: A79T C124S D268E G132D I101T

[Paragraph-level] PMCID: PMC7190743 Section: RESULTS PassageIndex: 8

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: C124S | Summary: The C124S variant did not exhibit a delay in eclosion compared to the empty vector control, indicating a functional alteration in its role in insulin signaling. Evidence Type: Functional | Mutation: G129E | Summary: The G129E variant exhibited eclosion significantly faster than the empty vector control, suggesting a functional change in its activity. Evidence Type: Functional | Mutation: N117S | Summary: The N117S variant slowed the developmental rate further than the wild-type, indicating a functional alteration in its role. Evidence Type: Functional | Mutation: Q298E | Summary: The Q298E variant also slowed the developmental rate further than the wild-type, suggesting a functional change in its activity.

Gene→Variant (gene-first): 5728:C124S 5728:G129E 5728:N117S 5728:Q298E

Genes: 5728

Variants: C124S G129E N117S Q298E

[Paragraph-level] PMCID: PMC7190743 Section: RESULTS PassageIndex: 5

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: C124S | Summary: The C124S variant is described as catalytically inactive and is involved in genetic interactions that alter PI3P metabolism, indicating a change in molecular function.

Gene→Variant (gene-first): 5728:C124S

Genes: 5728

Variants: C124S

[Paragraph-level] PMCID: PMC7190743 Section: RESULTS PassageIndex: 3

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: C124S | Summary: C124S is characterized as catalytically inactive for both protein and lipid phosphatase functions, indicating a significant alteration in molecular function. Evidence Type: Functional | Mutation: G129E | Summary: G129E is described as a lipid phosphatase-dead variant, which suggests it alters the biochemical function of the PTEN protein. Evidence Type: Functional | Mutation: Y138L | Summary: Y138L is identified as a protein phosphatase-dead variant, indicating a change in the molecular function of the PTEN protein. Evidence Type: Oncogenic | Mutation: C124S | Summary: C124S has been found in somatic cancer, suggesting it contributes to tumor development or progression. Evidence Type: Oncogenic | Mutation: R130X | Summary: R130X is associated with somatic cancer, indicating its role in tumor development or progression. Evidence Type: Oncogenic | Mutation: R335X | Summary: R335X is commonly associated with somatic cancer, suggesting it contributes to tumor development or progression.

Gene→Variant (gene-first): 5728:C124S 5728:G129E 5728:R130X 5728:R335X 5728:Y138L

Genes: 5728

Variants: C124S G129E R130X R335X Y138L

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

Evidence Type(s): Predictive, Oncogenic

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

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

Genes: 7157

Variants: R175H R248W R273H R282W

[Paragraph-level] PMCID: PMC3973211 Section: RESULTS PassageIndex: 10

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: R248 | Summary: The p53 R248 mutation was shown to induce higher expression of the CYP3A4 protein, indicating an alteration in molecular function. Evidence Type: Functional | Mutation: R282 | Summary: The p53 R282 mutation also induced higher expression of the CYP3A4 protein, demonstrating a change in molecular function. Evidence Type: Oncogenic | Mutation: R248 | Summary: The p53 R248 mutation is associated with increased expression of CYP3A4, suggesting its role in tumor development or progression. Evidence Type: Oncogenic | Mutation: R282 | Summary: The p53 R282 mutation contributes to increased expression of CYP3A4, indicating its involvement in tumor development or progression. Evidence Type: Functional | Mutation: R175H | Summary: The p53 R175H mutation was tested for its effects on CYP3A4 expression, indicating a potential alteration in molecular function. Evidence Type: Functional | Mutation: R273H | Summary: The p53 R273H mutation was also tested for its effects on CYP3A4 expression, suggesting a change in molecular function. Evidence Type: Oncogenic | Mutation: R175 | Summary: The p53 R175 mutation is associated with lower levels of CYP3A4 expression compared to mortality-associated mutations, indicating its role in tumor behavior. Evidence Type: Oncogenic | Mutation: R273 | Summary: The p53 R273 mutation is linked to lower levels of CYP3A4 expression compared to mortality-associated mutations, suggesting its involvement in tumor behavior.

Gene→Variant (gene-first): 7157:R175 7157:R175H 7157:R248 7157:R248W 7157:R273 7157:R273H 7157:R282 7157:R282W

Genes: 7157

Variants: R175 R175H R248 R248W R273 R273H R282 R282W

[Paragraph-level] PMCID: PMC3973211 Section: RESULTS PassageIndex: 8

Evidence Type(s): Prognostic, Oncogenic, Functional

Summary: Evidence Type: Prognostic | Mutation: R248Q/W | Summary: The R248Q/W mutations are associated with increased mortality in colorectal cancer, indicating a correlation with disease outcome independent of therapy. Evidence Type: Oncogenic | Mutation: R248W | Summary: The R248W mutation contributes to tumor development and progression, as it is classified among mortality-associated mutations in colorectal cancer. Evidence Type: Oncogenic | Mutation: R282W | Summary: The R282W mutation is also classified as a mortality-associated mutation, indicating its role in tumor development and progression. Evidence Type: Functional | Mutation: R273H | Summary: The R273H mutation is involved in specific gene enrichment profiles, suggesting alterations in molecular or biochemical function related to serine-hydrolase pathways.

Gene→Variant (gene-first): 7157:R175H 7157:R248Q/W 7157:R248W 7157:R273H 7157:R282W

Genes: 7157

Variants: R175H R248Q/W R248W R273H R282W

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

Evidence Type(s): Predictive

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

Gene→Variant (gene-first): 7157:R282

Genes: 7157

Variants: R282

[Paragraph-level] PMCID: PMC3973211 Section: RESULTS PassageIndex: 6

Evidence Type(s): Prognostic, Oncogenic

Summary: Evidence Type: Prognostic | Mutation: R248 | Summary: The R248 mutation is associated with shorter patient survival, indicating a correlation with disease outcome independent of therapy. Evidence Type: Prognostic | Mutation: R282 | Summary: The R282 mutation is associated with shorter patient survival, indicating a correlation with disease outcome independent of therapy. Evidence Type: Oncogenic | Mutation: R248 | Summary: The R248 mutation contributes to tumor development or progression, as evidenced by the survival analysis in mice carrying the mutation. Evidence Type: Oncogenic | Mutation: R282 | Summary: The R282 mutation contributes to tumor development or progression, as evidenced by the survival analysis in cancer patients.

Gene→Variant (gene-first): 7157:R175 7157:R248 7157:R273 7157:R282

Genes: 7157

Variants: R175 R248 R273 R282

[Paragraph-level] PMCID: PMC3973211 Section: RESULTS PassageIndex: 4

Evidence Type(s): Prognostic

Summary: Evidence Type: Prognostic | Mutation: Arg248 | Summary: Patients carrying p53 mutations at Arg248 had significantly shorter overall survival time compared to those with nonsense mutations, indicating a correlation with disease outcome. Evidence Type: Prognostic | Mutation: Arg282 | Summary: Similar to Arg248, mutations at Arg282 were associated with a higher hazard ratio in survival analysis, suggesting a negative impact on overall survival. Evidence Type: Prognostic | Mutation: Y220 | Summary: The mutation at Y220 showed similar survival curves to nonsense mutations, indicating it may not significantly affect disease outcome. Evidence Type: Prognostic | Mutation: G245 | Summary: G245 exhibited comparable survival curves to nonsense mutations, suggesting it does not have a significant impact on overall survival. Evidence Type: Prognostic | Mutation: R175 | Summary: The R175 mutation showed similar survival patterns to nonsense mutations, indicating no significant effect on patient survival. Evidence Type: Prognostic | Mutation: R273 | Summary: R273 displayed comparable survival curves to nonsense mutations, suggesting it does not significantly influence disease outcome. Evidence Type: Prognostic | Mutation: R249S | Summary: Very few cases of the R249S mutation were available for analysis, limiting the ability to draw conclusions about its impact on survival.

Gene→Variant (gene-first): 7157:Arg248 7157:Arg282 7157:G245 7157:R175 7157:R248 7157:R249S 7157:R273 7157:R282 7157:Y220

Genes: 7157

Variants: Arg248 Arg282 G245 R175 R248 R249S R273 R282 Y220

[Paragraph-level] PMCID: PMC3973211 Section: RESULTS PassageIndex: 2

Evidence Type(s): Prognostic

Summary: Evidence Type: Prognostic | Mutation: Arg248 | Summary: The mutation at Arg248 is associated with shorter patient survival, indicating a correlation with disease outcome independent of therapy. Evidence Type: Prognostic | Mutation: Arg282 | Summary: The mutation at Arg282 is associated with shorter patient survival, indicating a correlation with disease outcome independent of therapy.

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

Genes: 7157

Variants: Arg248 Arg282

[Paragraph-level] PMCID: PMC5481739 Section: RESULTS PassageIndex: 12

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: V716F | Summary: The DNMT3A-V716F mutation is predicted to affect methyltransferase activity, indicating a change in molecular function associated with this variant. Evidence Type: Oncogenic | Mutation: V716F | Summary: The somatic DNMT3A-V716F mutation is implicated in tumor development due to its association with a specific methylation signature in renal tumors.

Gene→Variant (gene-first): 1788:V716F

Genes: 1788

Variants: V716F

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

Evidence Type(s): Predictive, Oncogenic

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

Gene→Variant (gene-first): 3845:G12V

Genes: 3845

Variants: G12V

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

Evidence Type(s): Predictive, Functional, Oncogenic

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

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

Genes: 7158

Variants: L1363P p.L1363P

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

Evidence Type(s): Predictive, Oncogenic

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

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

Genes: 7158

Variants: L1363P

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

Evidence Type(s): Oncogenic, Diagnostic

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

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

Genes: 7158

Variants: L1363P p.L1363P

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

Evidence Type(s): Oncogenic, Functional

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

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

Genes: 7158

Variants: L1363P

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

Evidence Type(s): Functional, Oncogenic

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

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

Genes: 7158

Variants: L1363P p.L1363P

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

Evidence Type(s): Oncogenic

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

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

Genes: 7158

Variants: p.L1363P

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

Evidence Type(s): Functional, Predictive

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

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

Genes: 672 7158

Variants: leucine to proline p.L1363P p.L1407P

[Paragraph-level] PMCID: PMC7612117 Section: RESULTS PassageIndex: 8

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: p.L1363P | Summary: The variant p.L1363P alters the molecular function of BRCA1 by impairing its ability to bind PALB2 and exhibiting reduced activity in homologous recombination repair (HRR). Evidence Type: Oncogenic | Mutation: p.L1363P | Summary: The inability of the p.L1363P variant to effectively participate in HRR suggests that it may contribute to tumor development or progression due to its compromised function in DNA repair.

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

Genes: 7158

Variants: p.L1363P

[Paragraph-level] PMCID: PMC7612117 Section: RESULTS PassageIndex: 7

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: p.L1363P | Summary: The passage discusses the evaluation of the functional consequences of the Brca1 p.L1363P mutation in mouse embryonic fibroblasts, indicating that it alters molecular or biochemical function.

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

Genes: 7158

Variants: p.L1363P

[Paragraph-level] PMCID: PMC7612117 Section: RESULTS PassageIndex: 5

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: p.L1363P | Summary: The p.L1363P variant in Brca1 was analyzed functionally in vivo, showing a general growth defect in embryos, indicating an alteration in molecular or biochemical function. Evidence Type: Oncogenic | Mutation: p.L1363P | Summary: The absence of viable Brca1LP/LP mice and the observed growth defects suggest that the p.L1363P variant contributes to tumor development or progression, similar to other pathogenic mutations in Brca1.

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

Genes: 7158

Variants: p.L1363P

[Paragraph-level] PMCID: PMC7612117 Section: RESULTS PassageIndex: 4

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: p.L1363P | Summary: The homozygous Brca1 p.L1363P variant in mice is associated with embryonic lethality, indicating its role in tumor development or progression.

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

Genes: 7158

Variants: p.L1363P

[Paragraph-level] PMCID: PMC7612117 Section: RESULTS PassageIndex: 3

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: 4220T>C; p.L1407P | Summary: The variant p.L1407P disrupts the interaction of BRCA1 with PALB2 and is predicted to disable the alpha-helical structure of the coiled-coil domain, indicating a functional alteration. Evidence Type: Functional | Mutation: p.L1363P | Summary: The murine equivalent variant p.L1363P is predicted to disable the alpha-helical structure of the coiled-coil domain, indicating a functional alteration.

Gene→Variant (gene-first): 672:4220T>C 7158:p.L1363P 672:p.L1407P

Genes: 672 7158

Variants: 4220T>C p.L1363P p.L1407P

[Paragraph-level] PMCID: PMC7612117 Section: RESULTS PassageIndex: 2

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: p.L1363P | Summary: The passage indicates the generation of Brca1 p.L1363P mice, suggesting that this variant may alter molecular or biochemical function related to the Brca1 gene.

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

Genes: 7158

Variants: p.L1363P

[Paragraph-level] PMCID: PMC5822176 Section: RESULTS PassageIndex: 6

Evidence Type(s): Diagnostic

Summary: Evidence Type: Diagnostic | Mutation: K27M | Summary: The K27M mutation is associated with the diagnosis and classification of various grades of astrocytoma, as indicated by the correlation with MIB-1 labeling indices prior to testing.

Gene→Variant (gene-first): 3417:K27M

Genes: 3417

Variants: K27M

[Paragraph-level] PMCID: PMC5822176 Section: RESULTS PassageIndex: 5

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: K27M | Summary: The K27M mutation is associated with a lower frequency of ATRX mutation/loss in tumors, indicating its role in tumor development or progression.

Gene→Variant (gene-first): 3417:K27M

Genes: 3417

Variants: K27M

[Paragraph-level] PMCID: PMC5822176 Section: RESULTS PassageIndex: 4

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: K27M | Summary: The K27M mutation is associated with the transformation of low-grade gliomas to glioblastoma, indicating its role in tumor development and progression. Evidence Type: Functional | Mutation: K27M | Summary: The presence of diffuse H3 K27M immunostaining suggests that this mutation alters molecular function related to histone modification.

Gene→Variant (gene-first): 3417:K27M

Genes: 3417

Variants: K27M