[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 21

Evidence Type(s): Prognostic

Summary: Evidence Type: Prognostic | Mutation: K700E | Summary: The presence of the SF3B1 K700E mutation is associated with worse overall survival (OS) outcomes in the MDS cohort, indicating its role as an independent prognostic factor.

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

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 20

Evidence Type(s): Prognostic

Summary: Evidence Type: Prognostic | Mutation: K700E | Summary: The K700E SF3B1 mutation in low-grade MDS is associated with a trend for longer overall survival compared to non-K700E SF3B1 mutations, indicating a potential prognostic significance.

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

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 19

Evidence Type(s): Prognostic

Summary: Evidence Type: Prognostic | Mutation: K700E | Summary: The K700E mutation in SF3B1 is associated with significantly better overall survival (OS) compared to SF3B1 wild-type MDS, indicating its potential prognostic value in disease outcomes.

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

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 18

Evidence Type(s): Prognostic

Summary: Evidence Type: Prognostic | Mutation: K700E | Summary: The K700E mutation in SF3B1mut MDS is associated with a significantly improved overall survival (OS) compared to non-K700E patients, indicating its prognostic relevance in disease outcome.

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

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 17

Evidence Type(s): Prognostic

Summary: Evidence Type: Prognostic | Mutation: K700E | Summary: The K700E SF3B1 mutation does not show significant differences in overall survival (OS) compared to other SF3B1 mutations, indicating it may not correlate with disease outcome independent of therapy.

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

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 16

Evidence Type(s): Prognostic, Oncogenic

Summary: Evidence Type: Prognostic | Mutation: K700E | Summary: The K700E mutation in SF3B1 is associated with significantly better overall survival (OS) outcomes in MDS patients compared to SF3B1 wild-type patients, indicating its prognostic value. Evidence Type: Oncogenic | Mutation: K700E | Summary: The K700E mutation contributes to tumor development or progression in MDS, as evidenced by its association with improved survival outcomes in patients with this mutation compared to those without.

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

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 14

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: K700E | Summary: The SF3B1 K700E mutation is associated with distinct alternative splicing events and altered molecular functions in myelodysplastic syndromes (MDS), indicating its role in splicing and mRNA processing. Evidence Type: Oncogenic | Mutation: K700E | Summary: The SF3B1 K700E mutation contributes to tumor development and progression in myelodysplastic syndromes (MDS) by influencing the frequency and type of alternative splicing events.

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

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 13

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: K700E | Summary: The passage suggests that splicing analysis is being conducted to compare the K700E mutation with non-K700E mutated MDS, indicating that the K700E variant may alter molecular or biochemical function related to splicing.

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

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 12

Evidence Type(s): Prognostic, Diagnostic

Summary: Evidence Type: Prognostic | Mutation: K700E | Summary: The K700E mutation in SF3B1 is associated with lower comprehensive cytogenetic scoring system (CCSS) scores, indicating a potential correlation with disease outcome in patients. Evidence Type: Diagnostic | Mutation: K700E | Summary: The presence of the K700E mutation helps classify patients into different categories based on their cytogenetic aberrations, distinguishing them from non-K700E MDS patients.

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

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 11

Evidence Type(s): None

Summary: Not enough information in this passage.

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

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 10

Evidence Type(s): Diagnostic, Prognostic, Oncogenic

Summary: Evidence Type: Diagnostic | Mutation: K700E | Summary: The K700E mutation is associated with specific clinico-pathologic features that help classify and define the subtype of MDS in patients. Evidence Type: Prognostic | Mutation: K700E | Summary: The presence of the K700E mutation correlates with certain clinical features, such as a higher percentage of ring sideroblasts and ANC, which may indicate disease outcome independent of therapy. Evidence Type: Oncogenic | Mutation: K700E | Summary: The K700E mutation contributes to the development and progression of MDS, as indicated by its association with specific clinical features and classifications.

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

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 9

Evidence Type(s): Diagnostic

Summary: Evidence Type: Diagnostic | Mutation: K700E | Summary: The comparison between SF3B1 K700E and non-K700E mutated MDS suggests that the K700E variant may be used to classify or define a subtype of myelodysplastic syndromes (MDS).

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

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 8

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: K700E | Summary: The K700E mutation in SF3B1 is noted as the most frequent mutation in patients, indicating its contribution to tumor development in myelodysplastic syndromes (MDS).

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

Genes: 23451

Variants: K666 K700E R625

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 7

Evidence Type(s): Diagnostic

Summary: Evidence Type: Diagnostic | Mutation: K700E | Summary: The K700E mutation is mentioned in the context of defining and classifying subtypes of MDS, indicating its role in diagnostic criteria.

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

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: ABSTRACT PassageIndex: 12

Evidence Type(s): Prognostic, Diagnostic

Summary: Evidence Type: Prognostic | Mutation: K700E | Summary: The K700E mutation in SF3B1 is associated with a favorable prognosis in myelodysplastic syndromes, indicating its relevance in predicting disease outcomes. Evidence Type: Diagnostic | Mutation: K700E | Summary: The K700E mutation is used to refine the sub-classification and risk assessment criteria for myelodysplastic syndromes, highlighting its role in defining disease characteristics.

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

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: ABSTRACT PassageIndex: 10

Evidence Type(s): Prognostic, Diagnostic

Summary: Evidence Type: Prognostic | Mutation: K700E | Summary: The K700E mutation in SF3B1 is associated with significantly better overall survival (OS) in patients with myelodysplastic syndromes (MDS) compared to non-K700E mutations, indicating its prognostic value. Evidence Type: Diagnostic | Mutation: K700E | Summary: The presence of the K700E mutation in SF3B1 is important for risk-assessment in myelodysplastic syndromes (MDS), suggesting its role in classifying the disease.

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

Genes: 23451

Variants: K700E

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

Evidence Type(s): Oncogenic, Prognostic

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

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

Genes: 23451

Variants: K666 K700 K700E R625

[Paragraph-level] PMCID: PMC10015977 Section: ABSTRACT PassageIndex: 4

Evidence Type(s): Diagnostic, Prognostic

Summary: Evidence Type: Diagnostic | Mutation: K700E | Summary: The passage discusses the analysis of clinical-pathologic features and outcomes in MDS patients, indicating that K700E is used to explore differences in disease characteristics, which supports its role in diagnostic classification. Evidence Type: Prognostic | Mutation: K700E | Summary: The mention of outcomes in the context of K700E suggests that this variant may correlate with disease outcomes, supporting its prognostic significance in treatment-naive MDS patients.

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

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: ABSTRACT PassageIndex: 2

Evidence Type(s): Prognostic

Summary: Evidence Type: Prognostic | Mutation: K700E | Summary: The K700E mutation in SF3B1 is associated with a favorable prognosis in myelodysplastic syndromes (MDS).

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

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC3141770 Section: RESULTS PassageIndex: 6

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: H1047R | Summary: The H1047R mutation is associated with tumor development or progression, as indicated by its presence in patients with PTEN loss, suggesting a role in oncogenesis.

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

Genes: 5290

Variants: H1047R

[Paragraph-level] PMCID: PMC3141770 Section: RESULTS PassageIndex: 5

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: E542K | Summary: The E542K mutation is identified as a somatic variant that contributes to tumor development or progression, occurring in a sample from a patient. Evidence Type: Oncogenic | Mutation: H1047R | Summary: The H1047R mutation is a somatic variant that is associated with tumor development or progression, found in multiple samples. Evidence Type: Oncogenic | Mutation: T1052A | Summary: The T1052A mutation is a rare somatic variant that is implicated in tumor development or progression, identified in a single tumor sample.

Gene→Variant (gene-first): 5290:E542K 5290:H1047R 5728:T1052A

Genes: 5290 5728

Variants: E542K H1047R T1052A

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

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: T790M | Summary: The EGFR-T790M mutation is associated with response to the 3rd-generation EGFR-TKI osimertinib, indicating its predictive value for treatment sensitivity. Evidence Type: Oncogenic | Mutation: T790M | Summary: The presence of the EGFR-T790M mutation contributes to tumor progression, supporting its classification as an oncogenic variant.

Gene→Variant (gene-first): 1956:T790M

Genes: 1956

Variants: T790M

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

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: BRAFV600E | Summary: The BRAFV600E mutation is associated with response to BRAF inhibitors, indicating its predictive value for treatment outcomes in metastatic melanoma. Evidence Type: Oncogenic | Mutation: BRAFV600E | Summary: The BRAFV600E mutation contributes to tumor development in metastatic melanoma, supporting its classification as an oncogenic variant.

Gene→Variant (gene-first): 673:V600

Genes: 673

Variants: V600

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

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: L858R | Summary: The L858R mutation was mentioned in the context of a study that correlated mutations with response to therapy, although it was noted that this specific mutation was found in a non-responder. Evidence Type: Oncogenic | Mutation: L858R | Summary: The L858R mutation is a known missense mutation in exon 21 that contributes to tumor development or progression, as it is associated with EGFR mutations in cancer.

Gene→Variant (gene-first): 1956:L858R

Genes: 1956

Variants: L858R

[Paragraph-level] PMCID: PMC3542862 Section: RESULTS PassageIndex: 7

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: H1047R | Summary: The H1047R mutation in PIK3CA is associated with increased intracellular AKT phosphorylation, contributing to tumor development and progression. Evidence Type: Functional | Mutation: p.Glu542 | Summary: The p.Glu542 mutation in PIK3CA alters molecular function by increasing intracellular AKT phosphorylation, promoting cell survival and proliferation. Evidence Type: Oncogenic | Mutation: p.His1047 | Summary: The p.His1047 mutation in PIK3CA is linked to increased AKT phosphorylation, which is implicated in tumor development and progression.

Gene→Variant (gene-first): 5290:H1047R 5290:p.Glu542 5290:p.His1047

Genes: 5290

Variants: H1047R p.Glu542 p.His1047

[Paragraph-level] PMCID: PMC3542862 Section: RESULTS PassageIndex: 6

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: E542K | Summary: The E542K mutation is identified as a somatic mutation in the helical domain of PIK3CA, contributing to tumor development in macrodactyly patients. Evidence Type: Oncogenic | Mutation: H1047L | Summary: The H1047L mutation is a somatic mutation located in the kinase domain of PIK3CA, associated with tumor progression in macrodactyly patients. Evidence Type: Oncogenic | Mutation: H1047R | Summary: The H1047R mutation is a somatic mutation in the kinase domain of PIK3CA, contributing to tumor development in one of the macrodactyly patients. Evidence Type: Oncogenic | Mutation: R115P | Summary: The R115P mutation, identified through exome sequencing, is located in a linker sequence and is implicated in tumor development in macrodactyly patients.

Gene→Variant (gene-first): 5290:E542K 5290:H1047L 5290:H1047R 5163:R115P 5290:p.Glu542 5290:p.His1047

Genes: 5290 5163

Variants: E542K H1047L H1047R R115P p.Glu542 p.His1047

[Paragraph-level] PMCID: PMC3542862 Section: RESULTS PassageIndex: 5

Evidence Type(s): Diagnostic, Oncogenic

Summary: Evidence Type: Diagnostic | Mutation: R115P | Summary: The R115P mutation in PIK3CA is suggested as a likely candidate for macrodactyly, indicating its role in defining or classifying a disease. Evidence Type: Oncogenic | Mutation: R115L | Summary: The R115L mutation is associated with a squamous cell carcinoma, suggesting that mutations at p.Arg115 contribute to tumor development or progression. Evidence Type: Oncogenic | Mutation: p.Arg115 | Summary: The annotation of mutations at p.Arg115 in the context of cancer indicates their potential role in oncogenesis.

Gene→Variant (gene-first): 5290:R115L 5163:R115P 5290:p.Arg115

Genes: 5290 5163

Variants: R115L R115P p.Arg115

[Paragraph-level] PMCID: PMC3542862 Section: RESULTS PassageIndex: 4

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: C392G | Summary: The C392G variant in UBXN11 was identified as a candidate but was ultimately confirmed as a false positive, indicating it does not contribute to tumor development or progression. Evidence Type: Oncogenic | Mutation: R115P | Summary: The R115P mutation in PIK3CA was present in lesional tissue but absent in blood, suggesting it may contribute to tumor development or progression.

Gene→Variant (gene-first): 91544:C392G 5163:R115P

Genes: 91544 5163

Variants: C392G R115P

[Paragraph-level] PMCID: PMC2837563 Section: ABSTRACT PassageIndex: 6

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: Ala146Thr | Summary: The Ala146Thr mutation is associated with phenotypes similar to hotspot mutations, indicating its contribution to tumor development or progression. Evidence Type: Oncogenic | Mutation: Lys117Asn | Summary: The Lys117Asn mutation exhibits phenotypes similar to hotspot mutations, suggesting its role in tumor development or progression. Evidence Type: Functional | Mutation: Leu19Phe | Summary: The Leu19Phe mutation is described as having an attenuated phenotype, indicating a potential alteration in molecular or biochemical function. Evidence Type: Oncogenic | Mutation: Arg164Gln | Summary: The Arg164Gln mutation is phenotypically equivalent to wild-type K-Ras, but its presence in tumors suggests a potential role in tumor development or progression.

Gene→Variant (gene-first): 3845:Ala146Thr 3845:Arg164Gln 3845:Leu19Phe 3845:Lys117Asn

Genes: 3845

Variants: Ala146Thr Arg164Gln Leu19Phe Lys117Asn

[Paragraph-level] PMCID: PMC2837563 Section: RESULTS PassageIndex: 15

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: R164Q | Summary: The R164Q mutation showed relatively few changes in gene expression or reduced pathway activation compared to other mutants, indicating a potential alteration in molecular function. Evidence Type: Functional | Mutation: A146T | Summary: The A146T mutation influenced gene expression similarly to other activating mutations, suggesting an alteration in molecular function. Evidence Type: Functional | Mutation: K117N | Summary: The K117N mutation clustered with other mutants and influenced gene expression, indicating a potential alteration in molecular function. Evidence Type: Functional | Mutation: L19F | Summary: The L19F mutation influenced gene expression, albeit to a lesser extent than the other activating mutations, suggesting an alteration in molecular function. Evidence Type: Functional | Mutation: G13D | Summary: The G13D mutation is described as an activating mutation that influences gene expression, indicating an alteration in molecular function. Evidence Type: Functional | Mutation: Q61H | Summary: The Q61H mutation is characterized as an activating mutation that influences gene expression, indicating an alteration in molecular function.

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

Genes: 3845

Variants: A146T G13D K117N L19F Q61H R164Q

[Paragraph-level] PMCID: PMC2837563 Section: RESULTS PassageIndex: 13

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: A146T | Summary: The A146T mutation is associated with distinct phenotypic characteristics as indicated by transcription-profiling experiments, suggesting it alters molecular function. Evidence Type: Functional | Mutation: G12C | Summary: The G12C mutation is part of a gene cluster that shows similarity to wild-type K-Ras, indicating it may alter molecular function. Evidence Type: Functional | Mutation: G12D | Summary: The G12D mutation is included in a gene cluster that suggests it alters molecular function, as evidenced by transcription-profiling experiments. Evidence Type: Functional | Mutation: G12V | Summary: The G12V mutation is part of a gene cluster that indicates it alters molecular function, as shown by transcription-profiling experiments. Evidence Type: Functional | Mutation: G13D | Summary: The G13D mutation is associated with distinct phenotypic characteristics, suggesting it alters molecular function based on clustering analysis. Evidence Type: Functional | Mutation: K117N | Summary: The K117N mutation clusters with activating mutations, indicating it alters molecular function as suggested by transcription-profiling data. Evidence Type: Functional | Mutation: L19F | Summary: The L19F mutation is part of a subcluster that suggests it alters molecular function, consistent with Ras GTPase assay data. Evidence Type: Functional | Mutation: R164Q | Summary: The R164Q mutation, while initially surprising in its clustering, suggests an 'activating' phenotype, indicating it alters molecular function.

Gene→Variant (gene-first): 3845:A146T 3845:G12C 3845:G12D 3845:G12V 3845:G13D 3845:K117N 3845:L19F 3845:R164Q

Genes: 3845

Variants: A146T G12C G12D G12V G13D K117N L19F R164Q

[Paragraph-level] PMCID: PMC8688876 Section: RESULTS PassageIndex: 20

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: G12 | Summary: The G12 variant is associated with alterations in molecular function, particularly in relation to GAP-mediated hydrolysis and GTP-binding domain activity. Evidence Type: Functional | Mutation: G13 | Summary: The G13 variant exhibits changes in biochemical properties that affect RAF affinity and may influence downstream signaling mechanisms. Evidence Type: Functional | Mutation: Q61 | Summary: The Q61 variant is implicated in functional differences related to GTP hydrolysis and signaling pathways, as indicated by its interaction with RAS proteins.

Gene→Variant (gene-first): 3845:G12 3845:G13 3845:Q61

Genes: 3845

Variants: G12 G13 Q61

[Paragraph-level] PMCID: PMC8688876 Section: RESULTS PassageIndex: 19

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: G12 | Summary: The G12 mutation is associated with distinct vulnerabilities to the enzyme, indicating that it alters molecular or biochemical function. Evidence Type: Functional | Mutation: G12C | Summary: The G12C mutation conveys a different level of downstream activity, suggesting it alters molecular or biochemical function. Evidence Type: Functional | Mutation: G12D | Summary: The G12D mutation has been shown to have a specific level of downstream activity, indicating an alteration in molecular or biochemical function. Evidence Type: Functional | Mutation: G13 | Summary: The G13 mutation exhibits higher induction with higher variance, suggesting it alters molecular or biochemical function. Evidence Type: Functional | Mutation: Q61 | Summary: The Q61 mutation is part of the broader distribution of KRAS hotspot variants, indicating it alters molecular or biochemical function.

Gene→Variant (gene-first): 3845:G12 3845:G12C 3845:G12C/D 3845:G12D 3845:G13 3845:Q61

Genes: 3845

Variants: G12 G12C G12C/D G12D G13 Q61

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

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: G12S | Summary: G12S is predicted to have a decreased RAF affinity, indicating an alteration in molecular function. Evidence Type: Functional | Mutation: G13V | Summary: G13V is predicted to have an intermediate decrease in RAF affinity, suggesting a change in molecular function. Evidence Type: Functional | Mutation: Q61P | Summary: Q61P is predicted to have an intermediate decrease in RAF affinity, indicating an alteration in molecular function. Evidence Type: Functional | Mutation: A59T | Summary: A59T is predicted to have an intermediate decrease in RAF affinity, suggesting a change in molecular function. Evidence Type: Functional | Mutation: A146V | Summary: A146V is predicted to have an intermediate decrease in RAF affinity, indicating an alteration in molecular function. Evidence Type: Functional | Mutation: Q61H | Summary: Q61H shows relatively smaller changes in RAF affinity, suggesting a minor alteration in molecular function. Evidence Type: Functional | Mutation: A18D | Summary: A18D shows relatively smaller changes in RAF affinity, indicating a minor alteration in molecular function. Evidence Type: Functional | Mutation: Q22K | Summary: Q22K shows relatively smaller changes in RAF affinity, suggesting a minor alteration in molecular function. Evidence Type: Functional | Mutation: G13C | Summary: G13C is predicted to have RAF affinity comparable to WT, indicating no significant alteration in molecular function. Evidence Type: Functional | Mutation: G13S | Summary: G13S is predicted to have RAF affinity comparable to WT, indicating no significant alteration in molecular function. Evidence Type: Functional | Mutation: Q61R | Summary: Q61R is predicted to have RAF affinity comparable to WT, indicating no significant alteration in molecular function. Evidence Type: Functional | Mutation: L19F | Summary: L19F is predicted to have RAF affinity comparable to WT, indicating no significant alteration in molecular function. Evidence Type: Functional | Mutation: T74P | Summary: T74P is predicted to have RAF affinity comparable to WT, indicating no significant alteration in molecular function. Evidence Type: Functional | Mutation: K117N | Summary: K117N is predicted to have RAF affinity comparable to WT, indicating no significant alteration in molecular function. Evidence Type: Functional | Mutation: R164Q | Summary: R164Q is predicted to have RAF affinity comparable to WT, indicating no significant alteration in molecular function.

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

Genes: 3265 673 3845 4893 22882

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

[Paragraph-level] PMCID: PMC8688876 Section: RESULTS PassageIndex: 15

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: T74P | Summary: The T74P variant alters RAF affinity, indicating a change in molecular function related to tumor development. Evidence Type: Functional | Mutation: R164Q | Summary: The R164Q variant resembles hotspot variants in terms of RAF affinity, suggesting it alters molecular function. Evidence Type: Functional | Mutation: L19F | Summary: The L19F variant shows a pattern of RAF affinity similar to other variants, indicating a change in molecular function. Evidence Type: Functional | Mutation: K117N | Summary: The K117N variant's RAF affinity profile suggests it alters molecular function in a manner similar to other variants. Evidence Type: Functional | Mutation: A18D | Summary: The A18D variant resembles other variants in RAF affinity, indicating a change in molecular function. Evidence Type: Functional | Mutation: Q22K | Summary: The Q22K variant shows a similar RAF affinity profile to other variants, suggesting an alteration in molecular function. Evidence Type: Functional | Mutation: A146T | Summary: The A146T variant's RAF affinity profile indicates a change in molecular function related to tumor development. Evidence Type: Functional | Mutation: G12R | Summary: The G12R variant clusters with other variants in terms of RAF affinity, suggesting an alteration in molecular function. Evidence Type: Functional | Mutation: A59T | Summary: The A59T variant's clustering with other variants indicates a change in molecular function related to RAF affinity. Evidence Type: Functional | Mutation: A146V | Summary: The A146V variant's RAF affinity profile suggests it alters molecular function in a manner similar to other variants. Evidence Type: Functional | Mutation: G12C | Summary: The G12C variant shows a distinct RAF affinity profile, indicating a change in molecular function. Evidence Type: Functional | Mutation: G12C/D | Summary: The G12C/D variant's RAF affinity profile suggests an alteration in molecular function. Evidence Type: Functional | Mutation: G12V | Summary: The G12V variant's RAF affinity profile indicates a change in molecular function. Evidence Type: Functional | Mutation: G12S | Summary: The G12S variant shows a distinct RAF affinity profile, indicating a change in molecular function. Evidence Type: Functional | Mutation: Q61H | Summary: The Q61H variant's RAF affinity profile suggests it alters molecular function. Evidence Type: Functional | Mutation: Q61L | Summary: The Q61L variant shows a similar RAF affinity profile to other variants, indicating an alteration in molecular function. Evidence Type: Functional | Mutation: Q61P | Summary: The Q61P variant's RAF affinity profile indicates a change in molecular function. Evidence Type: Functional | Mutation: Q61R | Summary: The Q61R variant shows a distinct RAF affinity profile, indicating a change in molecular function. Evidence Type: Functional | Mutation: G13C | Summary: The G13C variant's RAF affinity profile suggests it alters molecular function. Evidence Type: Functional | Mutation: G13D | Summary: The G13D variant shows a similar RAF affinity profile to other variants, indicating an alteration in molecular function. Evidence Type: Functional | Mutation: G13V | Summary: The G13V variant's RAF affinity profile indicates a change in molecular function. Evidence Type: Functional | Mutation: G13S | Summary: The G13S variant shows a distinct RAF affinity profile, indicating a change in molecular function.

Gene→Variant (gene-first): 3845:A146T 3265:A146V 673:A18D 3265:A59T 3845:G12C 3845:G12C/D 3845:G12R 3845:G13C/D 3265:G13V 3845:K117N 3845:L19F 3845:Q22K 3845:Q61H/L 3845:Q61P 4893:Q61R 3845:R164Q 22882:T74P 22882:V/A

Genes: 3845 3265 673 4893 22882

Variants: A146T A146V A18D A59T G12C G12C/D G12R G13C/D G13V K117N L19F Q22K Q61H/L Q61P Q61R R164Q T74P V/A

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

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: A146T | Summary: A146T is suggested to alter molecular function by modulating GAP binding and changing the probability of locally unfolded conformations, impacting GAP-mediated hydrolysis rates. Evidence Type: Functional | Mutation: A146V | Summary: A146V is indicated to affect molecular function, as it associates with higher relative GAP-mediated hydrolysis compared to A146T. Evidence Type: Functional | Mutation: A59T | Summary: A59T is mentioned in the context of comparing its effects to G13D and Q61H, suggesting it may alter molecular function related to GAP-mediated hydrolysis. Evidence Type: Functional | Mutation: K117N | Summary: K117N is noted to have comparable effects to G13D and Q61H, indicating a potential alteration in molecular function. Evidence Type: Functional | Mutation: G12A/R | Summary: G12A/R is associated with comparable effects to G12S and is implicated in altering molecular function related to GAP-mediated hydrolysis. Evidence Type: Functional | Mutation: G12D | Summary: G12D is discussed in the context of conflicting reports regarding its effects, suggesting it may alter molecular function. Evidence Type: Functional | Mutation: G12S | Summary: G12S is indicated to have comparable effects to G12A/R and is involved in altering molecular function related to GAP-mediated hydrolysis. Evidence Type: Functional | Mutation: G13C | Summary: G13C is suggested to have a relatively lower effect compared to G13V, indicating a potential alteration in molecular function. Evidence Type: Functional | Mutation: G13D | Summary: G13D is mentioned in the context of its effects on GAP-mediated hydrolysis, suggesting it may alter molecular function. Evidence Type: Functional | Mutation: G13V | Summary: G13V is indicated to have a significant effect on GAP-mediated hydrolysis, suggesting an alteration in molecular function. Evidence Type: Functional | Mutation: L19F | Summary: L19F is compared to G13D and Q61H, indicating a potential alteration in molecular function. Evidence Type: Functional | Mutation: Q61H | Summary: Q61H is mentioned in relation to its effects on GAP-mediated hydrolysis, suggesting it may alter molecular function.

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

Genes: 3845 3265 673 22882

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

[Paragraph-level] PMCID: PMC8688876 Section: RESULTS PassageIndex: 12

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: A146V | Summary: The A146V mutation is associated with alterations in local stability and may modulate local unfolding, indicating a change in molecular function. Evidence Type: Functional | Mutation: G13C | Summary: The G13C mutation is part of a group of variants that relate to local stability and may affect local unfolding, suggesting a functional impact. Evidence Type: Functional | Mutation: G13V | Summary: The G13V mutation is included in a cluster of variants that influence local stability and local unfolding probabilities, indicating a functional alteration. Evidence Type: Functional | Mutation: K117N | Summary: The K117N mutation is identified as a non-hotspot variant that may affect local stability and local unfolding, suggesting a change in molecular function.

Gene→Variant (gene-first): 3265:A146V 3845:G13C 3265:G13V 3845:K117N

Genes: 3265 3845

Variants: A146V G13C G13V K117N

[Paragraph-level] PMCID: PMC8688876 Section: RESULTS PassageIndex: 5

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: A146T | Summary: The variant A146T is associated with increased GTP binding, indicating an alteration in molecular function. Evidence Type: Functional | Mutation: A146T/V | Summary: The variant A146T/V shows differences in behavior compared to hotspot variants, suggesting a functional impact on molecular activity. Evidence Type: Functional | Mutation: A59T | Summary: The variant A59T has a distinct profile among the mutants, indicating a potential alteration in molecular function. Evidence Type: Functional | Mutation: G12A/R | Summary: The G12A/R variant is part of a cluster that shows similarities with other variants, suggesting functional implications. Evidence Type: Functional | Mutation: G12A/R/S | Summary: The G12A/R/S variant is included in a cluster with other variants, indicating potential functional relevance. Evidence Type: Functional | Mutation: G12V/D | Summary: The G12V/D variant is associated with increased GTP binding, suggesting an alteration in molecular function. Evidence Type: Functional | Mutation: G13C | Summary: The G13C variant is part of a cluster that indicates functional similarities with other variants. Evidence Type: Functional | Mutation: G13V/D | Summary: The G13V/D variant is included in a cluster that suggests functional implications. Evidence Type: Functional | Mutation: K177N | Summary: The K177N variant is associated with increased GTP binding, indicating a potential alteration in molecular function. Evidence Type: Functional | Mutation: L19F | Summary: The L19F variant shows similarities with hotspot variants, suggesting functional relevance. Evidence Type: Functional | Mutation: Q22K | Summary: The Q22K variant is associated with increased GTP binding, indicating an alteration in molecular function. Evidence Type: Functional | Mutation: Q61 | Summary: The Q61 variant is part of a cluster that indicates functional implications. Evidence Type: Functional | Mutation: Q61H | Summary: The Q61H variant is associated with increased GTP binding, suggesting a potential alteration in molecular function. Evidence Type: Functional | Mutation: Q61L/P | Summary: The Q61L/P variant is included in a cluster that suggests functional implications. Evidence Type: Functional | Mutation: R164Q | Summary: The R164Q variant behaves like wild-type KRAS, indicating a potential alteration in molecular function. Evidence Type: Functional | Mutation: T74P | Summary: The T74P variant shows similarities with hotspot variants, suggesting functional relevance.

Gene→Variant (gene-first): 3845:A146T 3845:A146T/V 3265:A59T 3845:G12A/R 3845:G12A/R/S 3845:G12V/D 3845:G13C 3845:G13V/D 673:K177N 3845:L19F 3845:Q22K 3845:Q61 3845:Q61H 3845:Q61L/P 3845:R164Q 22882:T74P

Genes: 3845 3265 673 22882

Variants: A146T A146T/V A59T G12A/R G12A/R/S G12V/D G13C G13V/D K177N L19F Q22K Q61 Q61H Q61L/P R164Q T74P

[Paragraph-level] PMCID: PMC8688876 Section: RESULTS PassageIndex: 4

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: G12 | Summary: The G12 mutation is associated with alterations in the biochemical properties of the GTPase encoded by KRAS, affecting functions such as GTP binding and nucleotide exchange. Evidence Type: Functional | Mutation: G13 | Summary: The G13 mutation is linked to changes in the biochemical properties of the KRAS GTPase, influencing aspects like GTP binding and nucleotide exchange. Evidence Type: Functional | Mutation: Q61 | Summary: The Q61 mutation affects the biochemical properties of the KRAS GTPase, impacting functions such as GTP binding and nucleotide exchange. Evidence Type: Functional | Mutation: T74 | Summary: The T74 mutation is associated with alterations in the biochemical properties of the KRAS GTPase, influencing functions like GTP binding and nucleotide exchange. Evidence Type: Functional | Mutation: G12V | Summary: The G12V mutation is specifically noted for having all six biochemical measurements, indicating its significant impact on the functional properties of the KRAS GTPase.

Gene→Variant (gene-first): 3845:G12 3845:G12V 3845:G13 3845:Q61 22882:T74

Genes: 3845 22882

Variants: G12 G12V G13 Q61 T74

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

Evidence Type(s): Prognostic, Predictive

Summary: Evidence Type: Prognostic | Mutation: rs3786362 | Summary: The variant rs3786362 is associated with reduced progression-free survival (PFS) and overall survival (OS) in specific subgroups of metastatic colorectal cancer (mCRC) patients, indicating its potential role as a prognostic biomarker. Evidence Type: Predictive | Mutation: rs3786362 | Summary: The variant rs3786362 may serve as a predictive biomarker for survival in mCRC patients, particularly in certain subgroups, suggesting a correlation with treatment response or outcomes.

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

Genes: 7298

Variants: rs3786362

[Paragraph-level] PMCID: PMC7545690 Section: RESULTS PassageIndex: 14

Evidence Type(s): Prognostic

Summary: Evidence Type: Prognostic | Mutation: rs3786362 | Summary: The variant rs3786362 is associated with mCRC survival, indicating its potential role in correlating with disease outcome independent of therapy.

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

Genes: 7298

Variants: rs3786362

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

Evidence Type(s): Predictive

Summary: Evidence Type: Predictive | Mutation: rs3786362 | Summary: The G allele of rs3786362 in TYMS is associated with reduced disease control rate (DCR) in mCRC patients undergoing first-line chemotherapy, indicating its potential role in predicting treatment response.

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

Genes: 7298

Variants: rs3786362

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

Evidence Type(s): Predictive

Summary: Evidence Type: Predictive | Mutation: rs3786362 | Summary: The variant rs3786362 in TYMS correlates with the disease control rate (DCR) in metastatic colorectal cancer (mCRC) patients, indicating its potential role in predicting treatment response.

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

Genes: 7298

Variants: rs3786362

[Paragraph-level] PMCID: PMC7545690 Section: RESULTS PassageIndex: 11

Evidence Type(s): Prognostic

Summary: Evidence Type: Prognostic | Mutation: rs3786362 | Summary: The variant rs3786362 is associated with reduced progression-free survival (PFS) and overall survival (OS) in metastatic colorectal cancer (mCRC) patients, indicating its prognostic significance.

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

Genes: 7298

Variants: rs3786362

[Paragraph-level] PMCID: PMC7545690 Section: RESULTS PassageIndex: 10

Evidence Type(s): Prognostic

Summary: Evidence Type: Prognostic | Mutation: rs3786362 | Summary: The variant TYMS rs3786362 is associated with reduced overall survival (OS) and progression-free survival (PFS), indicating its correlation with disease outcome independent of therapy. Evidence Type: Prognostic | Mutation: rs3786362 | Summary: The AG genotype of rs3786362 in TYMS is correlated with reduced PFS and OS compared to the AA genotype, further supporting its role in predicting disease outcomes. Evidence Type: Prognostic | Mutation: rs3786362 | Summary: Carriers of the G allele of rs3786362 are prone to shorter PFS and OS times, reinforcing its prognostic significance in the context of cancer survival.

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

Genes: 7298

Variants: rs3786362

[Paragraph-level] PMCID: PMC7545690 Section: RESULTS PassageIndex: 9

Evidence Type(s): Prognostic

Summary: Evidence Type: Prognostic | Mutation: rs3786362 | Summary: The variant rs3786362 in TYMS is associated with mCRC survival, indicating its potential role in predicting disease outcome independent of therapy.

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

Genes: 7298

Variants: rs3786362

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

Evidence Type(s): Prognostic

Summary: Evidence Type: Prognostic | Mutation: rs3786362 | Summary: The SNP rs3786362 in TYMS is correlated with reduced progression-free survival (PFS) in metastatic colorectal cancer (mCRC) patients, indicating its potential as a prognostic marker. Evidence Type: Prognostic | Mutation: rs369803 | Summary: The SNP rs369803 in FOLH1 is associated with progression-free survival (PFS) in mCRC patients, suggesting it may serve as a prognostic indicator for disease outcome.

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

Genes: 10841 2346 7298 113235

Variants: rs10432965 rs369803 rs3786362 rs4795436

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

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: B-RAFV600E | Summary: The B-RAFV600E mutation is associated with treatment responses in patients with melanoma, thyroid cancer, and low-grade serous ovarian cancer, indicating its predictive value for therapy outcomes. Evidence Type: Oncogenic | Mutation: B-RAFV600E | Summary: The B-RAFV600E mutation is implicated in tumor development and progression in various cancers, including melanoma and thyroid cancer, supporting its classification as an oncogenic variant.

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

Genes: 673

Variants: B-RAFV600E

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

Evidence Type(s): Predictive, Oncogenic

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

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

Genes: 673

Variants: B-RAFV600E

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

Evidence Type(s): Predictive, Oncogenic

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

Gene→Variant (gene-first): 3845:G13D

Genes: 3845

Variants: G13D

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

Evidence Type(s): Predictive, Oncogenic

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

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

Genes: 673

Variants: B-RAFV600E

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

Evidence Type(s): Oncogenic

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

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

Genes: 5290

Variants: E545K H1047R

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

Evidence Type(s): Predictive

Summary: Evidence Type: Predictive | Mutation: A775dupYVMA | Summary: The HER2 A775dupYVMA mutation is associated with an overall response rate (ORR) of 20.0%, indicating its potential predictive value for therapy response. Evidence Type: Predictive | Mutation: G776delinsVC | Summary: The G776delinsVC mutation shows an ORR of 27.3%, suggesting it may also have predictive implications for treatment response.

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

Genes: 2064

Variants: A775dupYVMA G776delinsVC

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

Evidence Type(s): Predictive, Oncogenic

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

Gene→Variant (gene-first): 3845:G12D

Genes: 3845

Variants: G12D

[Paragraph-level] PMCID: PMC11551396 Section: RESULTS PassageIndex: 18

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: C797 | Summary: The mutation C797 is involved in forming a covalent bond with an inhibitor, indicating that it alters molecular or biochemical function. Evidence Type: Functional | Mutation: T790 | Summary: The mutation T790 is described in the context of its interaction with a quinoline substituent, suggesting it alters molecular or biochemical function.

Gene→Variant (gene-first): 1956:C797 1956:T790

Genes: 1956

Variants: C797 T790

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

Evidence Type(s): Oncogenic

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

Gene→Variant (gene-first): 1956:T790

Genes: 1956

Variants: T790

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

Evidence Type(s): Functional, Oncogenic

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

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

Genes: 1956

Variants: C797 T790M V948R

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

Evidence Type(s): Oncogenic

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

Gene→Variant (gene-first): 1956:T790

Genes: 1956

Variants: T790

[Paragraph-level] PMCID: PMC11551396 Section: RESULTS PassageIndex: 14

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: T790M | Summary: The T790M mutation is associated with altered molecular or biochemical function as it is studied in the context of cocrystal structures with various inhibitors. Evidence Type: Functional | Mutation: V948R | Summary: The V948R mutation is associated with altered molecular or biochemical function as it is studied in the context of cocrystal structures with various inhibitors.

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

Genes: 1956

Variants: T790M V948R

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

Evidence Type(s): Predictive, Oncogenic

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

Gene→Variant (gene-first): 1956:L858R

Genes: 1956

Variants: L858R

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

Evidence Type(s): Predictive

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

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

Genes: 1956

Variants: L858R T790M

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

Evidence Type(s): Predictive, Oncogenic

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

Gene→Variant (gene-first): 1956:L858R

Genes: 1956

Variants: L858R

[Paragraph-level] PMCID: PMC11551396 Section: RESULTS PassageIndex: 4

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: L858R | Summary: The L858R mutation alters the enzyme kinetic parameters of EGFR, demonstrating a significant increase in catalytic efficiency compared to wild-type EGFR. Evidence Type: Functional | Mutation: T790M | Summary: The T790M mutation is associated with altered enzyme kinetics, showing increased catalytic rates compared to wild-type EGFR. Evidence Type: Functional | Mutation: Glu4 | Summary: The Glu4 mutation is evaluated in terms of its impact on enzyme kinetics, indicating a functional alteration in comparison to wild-type EGFR.

Gene→Variant (gene-first): 7294:Glu4 1956:L858R 1956:T790M

Genes: 7294 1956

Variants: Glu4 L858R T790M

[Paragraph-level] PMCID: PMC6843359 Section: RESULTS PassageIndex: 11

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: S310F | Summary: The S310F HER2 variant alters the interaction efficiency with EGFR, as indicated by the fluorescence intensity measurements in the cell lysates, suggesting a change in molecular function.

Gene→Variant (gene-first): 2064:S310F

Genes: 2064

Variants: S310F

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

Evidence Type(s): Functional, Oncogenic

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

Gene→Variant (gene-first): 2064:S310F

Genes: 2064

Variants: S310F

[Paragraph-level] PMCID: PMC6843359 Section: RESULTS PassageIndex: 9

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: S310F | Summary: The S310F HER2 mutant alters molecular interactions by forming heterodimers with the EGFR, indicating a change in biochemical function.

Gene→Variant (gene-first): 2064:S310F

Genes: 2064

Variants: S310F

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

Evidence Type(s): Oncogenic, Predictive

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

Gene→Variant (gene-first): 2064:S310F

Genes: 2064

Variants: S310F

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

Evidence Type(s): Oncogenic

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

Gene→Variant (gene-first): 2064:S310F

Genes: 2064

Variants: S310F

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

Evidence Type(s): Functional, Oncogenic

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

Gene→Variant (gene-first): 2064:S310F

Genes: 2064

Variants: S310F

[Paragraph-level] PMCID: PMC6843359 Section: RESULTS PassageIndex: 5

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: S310F | Summary: The S310F mutation was identified in a bladder cancer cell line, and its expression was analyzed through molecular techniques, indicating an alteration in molecular function.

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

Genes: 2064

Variants: S310 S310F

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

Evidence Type(s): Functional, Oncogenic

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

Gene→Variant (gene-first): 2064:S310F

Genes: 2064

Variants: S310F

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

Evidence Type(s): Predictive

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

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

Genes: 2064

Variants: G309 G309A G309E S309A S310 S310F S310Y

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

Evidence Type(s): Predictive, Functional

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

Gene→Variant (gene-first): 2064:S310F

Genes: 2064

Variants: S310F

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

Evidence Type(s): Oncogenic, Functional

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

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

Genes: 3815

Variants: D816V L576P N822K T670I V559D V654A

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

Evidence Type(s): Predictive, Oncogenic, Functional

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

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

Genes: 2064 673 324

Variants: p.L755S p.N581S p.Q1429fs

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

Evidence Type(s): Oncogenic, Functional

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

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

Genes: 3791 3845 4893 79811 673

Variants: A163G G12D G12N G13D Q61H Q61L R106H V600E

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

Evidence Type(s): Oncogenic

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

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

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

Evidence Type(s): Predictive, Prognostic

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

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

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

Evidence Type(s): Predictive, Oncogenic

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

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

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

Evidence Type(s): Oncogenic

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

Gene→Variant (gene-first): 4893:G13C

Genes: 4893

Variants: G13C

[Paragraph-level] PMCID: PMC10011885 Section: RESULTS PassageIndex: 15

Evidence Type(s): Diagnostic, Prognostic, Predictive

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

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paragraph-level] PMCID: PMC10011885 Section: RESULTS PassageIndex: 3

Evidence Type(s): Oncogenic, Diagnostic

Summary: Evidence Type: Oncogenic | Mutation: V600E | Summary: The BRAF V600E mutation is associated with tumor development or progression in various cancers, including non-colorectal cancers. Evidence Type: Diagnostic | Mutation: V600E | Summary: The presence of the BRAF V600E mutation is used to classify patients with selected cancers, confirming their mutation-positive status.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

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

Evidence Type(s): Predictive

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

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

Genes: 1956

Variants: D770 G770 Y764insFQEA

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

Evidence Type(s): Predictive, Oncogenic

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

Gene→Variant (gene-first): 1956:G770

Genes: 1956

Variants: G770

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

Evidence Type(s): Predictive, Oncogenic

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

Gene→Variant (gene-first): 1956:G770

Genes: 1956

Variants: G770

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

Evidence Type(s): Predictive, Oncogenic

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

Gene→Variant (gene-first): 1956:G770

Genes: 1956

Variants: G770

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

Evidence Type(s): Oncogenic, Diagnostic

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

Gene→Variant (gene-first): 1956:G770

Genes: 1956

Variants: G770

[Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 8

Evidence Type(s): Predictive

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

Gene→Variant (gene-first): 1956:G770

Genes: 1956

Variants: G770

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

Evidence Type(s): Predictive, Functional

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

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

Genes: 1956

Variants: V769dupASV

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

Evidence Type(s): Predictive, Oncogenic

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

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

Genes: 1956

Variants: V769dupASV

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

Evidence Type(s): Predictive, Functional

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

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

Genes: 1956

Variants: D770_N771insSVD V769dupASV Y764insFQEA

[Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 4

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: G770 | Summary: The passage discusses the preclinical characterization of an EGFR Exon 20 Insertion Mutant with a G770 equivalence, indicating that this variant alters molecular or biochemical function.

Gene→Variant (gene-first): 1956:G770

Genes: 1956

Variants: G770

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

Evidence Type(s): Oncogenic, Functional

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

Gene→Variant (gene-first): 1956:G770

Genes: 1956

Variants: G770

[Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 2

Evidence Type(s): None

Summary: Not enough information in this passage.

Gene→Variant (gene-first): 1956:G770

Genes: 1956

Variants: G770

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

Evidence Type(s): Oncogenic

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

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

Genes: 1956

Variants: L858R L861Q S768I T790M

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

Evidence Type(s): Predictive, Prognostic, Oncogenic

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

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

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

Evidence Type(s): Predictive, Oncogenic

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

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

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

Evidence Type(s): Predictive, Diagnostic, Oncogenic

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

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

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

Evidence Type(s): Predictive, Oncogenic

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

Gene→Variant (gene-first): 1956:T790M

Genes: 1956

Variants: T790M

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

Evidence Type(s): Oncogenic

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

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

Genes: 1956

Variants: L858R T790M

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

Evidence Type(s): Predictive, Oncogenic

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

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

Genes: 6098

Variants: G2032R

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

Evidence Type(s): Predictive, Oncogenic

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

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

Genes: 6098

Variants: G2032R

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

Evidence Type(s): Predictive, Oncogenic

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

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

Genes: 6098

Variants: G2032R

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

Evidence Type(s): Predictive, Functional

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

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

Genes: 2261 2260

Variants: V555M V561M

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

Evidence Type(s): Predictive

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

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

Genes: 2261

Variants: K650E N540K

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

Evidence Type(s): Predictive, Functional, Oncogenic

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

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

Genes: 2263 2261

Variants: I538 I538V K650E N540 N540K N540S R669G V555M

[Paragraph-level] PMCID: PMC5029699 Section: RESULTS PassageIndex: 30

Evidence Type(s): Predictive, Functional

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

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

Genes: 2263 2261

Variants: I538V K650E N540K N540S R669G V555M

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

Evidence Type(s): Oncogenic, Predictive

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

Gene→Variant (gene-first): 2261:V555M

Genes: 2261

Variants: V555M

[Paragraph-level] PMCID: PMC5029699 Section: RESULTS PassageIndex: 27

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: D641 | Summary: The D641 mutation is involved in forming a hydrogen bond with the drug JNJ42756493, indicating that it alters molecular interactions within the FGFR1 protein. Evidence Type: Functional | Mutation: L630 | Summary: The L630 mutation is part of a shallow pocket that interacts with the terminal isopropyl group of JNJ42756493, suggesting it plays a role in the molecular function of the FGFR1 binding site. Evidence Type: Functional | Mutation: V561 | Summary: The V561 mutation is described as the gatekeeper residue that is involved in the binding of JNJ42756493, indicating its role in the molecular function of FGFR1.

Gene→Variant (gene-first): 2260:D641 2260:L630 2260:V561

Genes: 2260

Variants: D641 L630 V561

[Paragraph-level] PMCID: PMC5029699 Section: RESULTS PassageIndex: 24

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: K650E | Summary: The K650E mutation alters the conformation of the A-loop, impacting the allosteric communication within the FGFR2 kinase domain. Evidence Type: Functional | Mutation: R669G | Summary: The R669G mutation is suggested to disrupt inhibitory interactions near the A-loop, contributing to changes in the allosteric mechanism of FGFR1. Evidence Type: Functional | Mutation: R675G | Summary: The R675G mutation is implicated in altering the allosteric mechanism of FGFR1 by affecting the interactions involving the A-loop. Evidence Type: Functional | Mutation: R675 | Summary: The R675 mutation is associated with changes in the allosteric communication within the FGFR1 kinase domain, similar to the R675G variant.

Gene→Variant (gene-first): 2261:K650E 2261:R669G 2260:R675 2260:R675G

Genes: 2261 2260

Variants: K650E R669G R675 R675G

[Paragraph-level] PMCID: PMC5029699 Section: RESULTS PassageIndex: 23

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: R669G | Summary: The R669G mutation in FGFR3 alters molecular interactions and promotes an active conformation, as indicated by significant chemical shift perturbations observed in NMR studies.

Gene→Variant (gene-first): 2261:R669G

Genes: 2261

Variants: R669G

[Paragraph-level] PMCID: PMC5029699 Section: RESULTS PassageIndex: 22

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: R675G | Summary: The R675G mutation alters the molecular interactions within the FGFR1 kinase domain, leading to a change in conformation that affects the overall structure and function of the protein. Evidence Type: Functional | Mutation: R675 | Summary: The R675 residue is involved in critical hydrogen bonding and van der Waals interactions that are essential for maintaining the inactive conformation of FGFR1, indicating its role in molecular function. Evidence Type: Functional | Mutation: H650 | Summary: The H650 residue participates in hydrogen bonding with R675, which is crucial for the structural integrity of the inactive FGFR1 kinase domain, highlighting its functional importance. Evidence Type: Functional | Mutation: Y653 | Summary: The Y653 residue is involved in van der Waals interactions with R675, contributing to the structural stability of the FGFR1 kinase domain and its functional state.

Gene→Variant (gene-first): 2261:H650 2260:R675 2260:R675G 2263:Y653

Genes: 2261 2260 2263

Variants: H650 R675 R675G Y653

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

Evidence Type(s): Oncogenic, Functional

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

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

Genes: 2260 2261

Variants: R to G R669 R675G

[Paragraph-level] PMCID: PMC5029699 Section: RESULTS PassageIndex: 20

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: R669G | Summary: The passage discusses the activation mechanism of the FGFR3 R669G mutation, indicating that it alters molecular or biochemical function.

Gene→Variant (gene-first): 2261:R669G

Genes: 2261

Variants: R669G

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

Evidence Type(s): Functional, Oncogenic

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

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

Genes: 2261 2263 2260

Variants: D617G E466K G637W R669

[Paragraph-level] PMCID: PMC5029699 Section: RESULTS PassageIndex: 18

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: R669G | Summary: The R669G mutation in FGFR3 is associated with altered molecular function, as indicated by enhanced downstream signaling and increased FGFR3 phosphorylation in the NIH3T3 cell line.

Gene→Variant (gene-first): 2261:R669G

Genes: 2261

Variants: R669G

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

Evidence Type(s): Functional, Oncogenic

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

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

Genes: 2261

Variants: G697C K650E N540K

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

Evidence Type(s): Functional, Oncogenic

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

Gene→Variant (gene-first): 2261:K650E

Genes: 2261

Variants: K650E

[Paragraph-level] PMCID: PMC5029699 Section: RESULTS PassageIndex: 15

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: D617G | Summary: The D617G mutation completely abolished kinase activity, indicating that it alters molecular function. Evidence Type: Functional | Mutation: G637W | Summary: The G637W mutation also resulted in kinase inactivation, demonstrating an alteration in molecular function.

Gene→Variant (gene-first): 2261:D617 2261:D617G 2261:G to W 2260:G637 2260:G637W

Genes: 2261 2260

Variants: D617 D617G G to W G637 G637W

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

Evidence Type(s): Functional, Oncogenic

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

Gene→Variant (gene-first): 2261:G697C

Genes: 2261

Variants: G697C

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

Evidence Type(s): Functional, Predictive

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

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

Genes: 2260 2261

Variants: D641G D641N V555 V555M

[Paragraph-level] PMCID: PMC5029699 Section: RESULTS PassageIndex: 12

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: K650E | Summary: The K650E mutation significantly increases auto-phosphorylation of FGFR3 KD, indicating an alteration in molecular function. Evidence Type: Functional | Mutation: K650N | Summary: The K650N mutation results in less activation of FGFR3 KD auto-phosphorylation compared to K650E, suggesting it alters molecular function. Evidence Type: Functional | Mutation: N540K | Summary: The N540K mutation leads to a substantial increase in auto-phosphorylation of FGFR3 KD, indicating a change in molecular function. Evidence Type: Functional | Mutation: N540S | Summary: The N540S mutation is associated with reduced activation of FGFR3 KD auto-phosphorylation, indicating an alteration in molecular function. Evidence Type: Functional | Mutation: R669G | Summary: The R669G mutation is the most activating variant in the assay, resulting in increased auto-phosphorylation of FGFR3 KD, indicating a change in molecular function. Evidence Type: Functional | Mutation: R669Q | Summary: The R669Q mutation also results in increased auto-phosphorylation of FGFR3 KD, indicating an alteration in molecular function. Evidence Type: Functional | Mutation: I538V | Summary: The I538V mutation is the least activating among variants that increase FGFR3 KD auto-phosphorylation, suggesting it alters molecular function.

Gene→Variant (gene-first): 2263:I538V 2261:K650E 2261:K650N 2261:N540K 2261:N540S 2261:R669G 2261:R669Q

Genes: 2263 2261

Variants: I538V K650E K650N N540K N540S R669G R669Q

[Paragraph-level] PMCID: PMC5029699 Section: RESULTS PassageIndex: 11

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: K650 | Summary: The mutation FGFR3 K650 has been assessed for its functional impact, indicating that it alters molecular or biochemical function. Evidence Type: Functional | Mutation: N540K | Summary: The mutation FGFR3 N540K has been assessed for its functional impact, indicating that it alters molecular or biochemical function.

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

Genes: 2261

Variants: K650 N540K

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

Evidence Type(s): Oncogenic, Functional

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

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

Genes: 2263 2261

Variants: I538 K650 N540 R669

[Paragraph-level] PMCID: PMC5029699 Section: RESULTS PassageIndex: 6

Evidence Type(s): None

Summary: Not enough information in this passage.

Gene→Variant (gene-first): 2261:G697 2263:I538 2261:K650 2261:N540 2261:R669

Genes: 2261 2263

Variants: G697 I538 K650 N540 R669

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

Evidence Type(s): Oncogenic

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

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

Genes: 2261

Variants: K650 N540 N540K

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

Evidence Type(s): Oncogenic

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

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

Genes: 2261

Variants: G697 G697C K650 N540

[Paragraph-level] PMCID: PMC3244026 Section: RESULTS PassageIndex: 9

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: V345fs | Summary: The V345fs ETV6 mutant is functionally inactive, showing no transcriptional repression activity and exhibiting dominant-negative activity compared to wild-type ETV6. Evidence Type: Functional | Mutation: N356fs | Summary: The N356fs ETV6 mutant is functionally inactive, demonstrating a lack of transcriptional repression activity and exhibiting dominant-negative activity compared to wild-type ETV6. Evidence Type: Functional | Mutation: Y103fs | Summary: The Y103fs ETV6 mutant is functionally inactive, with no transcriptional repression activity and exhibiting dominant-negative activity compared to wild-type ETV6. Evidence Type: Functional | Mutation: S105fs | Summary: The S105fs ETV6 mutant is functionally inactive, showing no transcriptional repression activity and exhibiting dominant-negative activity compared to wild-type ETV6.

Gene→Variant (gene-first): 2120:N356fs 2120:S105fs 2120:V345fs 2120:Y103fs

Genes: 2120

Variants: N356fs S105fs V345fs Y103fs

[Paragraph-level] PMCID: PMC3244026 Section: RESULTS PassageIndex: 8

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: Y103fs | Summary: The Y103fs mutation leads to the expression of N-terminal truncated protein products that alter the molecular function of the ETV6 protein. Evidence Type: Functional | Mutation: S105fs | Summary: The S105fs mutation results in the activation of internal translation initiation sites and the expression of truncated ETV6 protein products, indicating a change in molecular function. Evidence Type: Functional | Mutation: V345fs | Summary: The V345fs mutation causes the expression of C-terminal truncated polypeptides, which alters the molecular function of the ETV6 protein. Evidence Type: Functional | Mutation: N356fs | Summary: The N356fs mutation results in the expression of C-terminal truncated ETV6 proteins, indicating a change in molecular function.

Gene→Variant (gene-first): 2120:N356fs 2120:S105fs 2120:V345fs 2120:Y103fs

Genes: 2120

Variants: N356fs S105fs V345fs Y103fs

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

Evidence Type(s): Oncogenic, Functional

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

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

Genes: 3091 6921 5979 3855 7409

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

[Paragraph-level] PMCID: PMC9402235 Section: RESULTS PassageIndex: 8

Evidence Type(s): None

Summary: Not enough information in this passage.

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

Genes: 3091

Variants: c.236A>G p.Tyr79Cys

[Paragraph-level] PMCID: PMC9402235 Section: RESULTS PassageIndex: 6

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: c.236A>G | Summary: The c.236A>G variant is associated with mosaicism, suggesting it alters molecular or biochemical function. Evidence Type: Functional | Mutation: p.Tyr79Cys | Summary: The p.Tyr79Cys variant is associated with mosaicism, indicating it alters molecular or biochemical function.

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

Genes: 3091

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

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

Evidence Type(s): Functional, Oncogenic

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

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

Genes: 3091

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

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

Evidence Type(s): Oncogenic, Functional

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

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

Genes: 7010 3845

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

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

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

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

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

Genes: 7158

Variants: p.L1363P

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

Evidence Type(s): Predictive, Oncogenic

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

Gene→Variant (gene-first): 1956:T790M

Genes: 1956

Variants: T790M

[Paragraph-level] PMCID: PMC3378484 Section: RESULTS PassageIndex: 24

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: H1047 | Summary: The mutation H1047 is associated with altered lipid binding capabilities among the p110 isoforms, indicating a change in molecular function. Evidence Type: Functional | Mutation: H1047L | Summary: The mutation H1047L shows increased lipid binding levels compared to other p110 isoforms, suggesting a modification in biochemical function.

Gene→Variant (gene-first): 5290:H1047 5290:H1047L

Genes: 5290

Variants: H1047 H1047L

[Paragraph-level] PMCID: PMC3378484 Section: RESULTS PassageIndex: 22

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: H1047R | Summary: The H1047R mutation in p110alpha appears to induce a global conformational change that may impact the molecular activity of the kinase C-lobe, suggesting a functional alteration in its biochemical properties.

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

Genes: 5290

Variants: H1047R

[Paragraph-level] PMCID: PMC3378484 Section: RESULTS PassageIndex: 20

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: C420R | Summary: The C420R mutation alters the molecular interactions within the C2 domain, potentially affecting lipid binding due to changes in hydrophobicity. Evidence Type: Functional | Mutation: N564D | Summary: The N564D mutation modifies the polar contacts in the C2 domain, which may influence the interaction with phospholipid headgroups. Evidence Type: Functional | Mutation: E545K | Summary: The E545K mutation disrupts contacts in the C2/helical-nSH2 region, potentially exposing hydrophobic areas that could affect lipid binding.

Gene→Variant (gene-first): 5290:C420 5290:C420R 5290:E545K 5295:N345 5295:N564 5295:N564D

Genes: 5290 5295

Variants: C420 C420R E545K N345 N564 N564D

[Paragraph-level] PMCID: PMC3378484 Section: RESULTS PassageIndex: 19

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: G1049R | Summary: The G1049R mutation alters molecular function by exhibiting high levels of hydrophobic and electrostatic binding to lipids upon phosphopeptide activation. Evidence Type: Functional | Mutation: H1047L | Summary: The H1047L mutation alters molecular function by exhibiting high levels of hydrophobic and electrostatic binding to lipids upon phosphopeptide activation. Evidence Type: Functional | Mutation: H1047R | Summary: The H1047R mutation alters molecular function by exhibiting high levels of hydrophobic and electrostatic binding to lipids upon phosphopeptide activation.

Gene→Variant (gene-first): 5290:G1049R 5290:H1047L 5290:H1047R

Genes: 5290

Variants: G1049R H1047L H1047R

[Paragraph-level] PMCID: PMC3378484 Section: RESULTS PassageIndex: 18

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: C420R | Summary: The C420R mutation alters molecular function by displaying high levels of hydrophobic interaction with neutral lipids in the basal state. Evidence Type: Functional | Mutation: E545K | Summary: The E545K mutation alters molecular function by displaying high levels of hydrophobic interaction with neutral lipids in the basal state. Evidence Type: Functional | Mutation: N564D | Summary: The N564D mutation alters molecular function by displaying high levels of hydrophobic interaction with neutral lipids in the basal state.

Gene→Variant (gene-first): 5290:C420R 5290:E545K 5295:N564D

Genes: 5290 5295

Variants: C420R E545K N564D

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

Evidence Type(s): Oncogenic

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

Gene→Variant (gene-first): 5290:E545K

Genes: 5290

Variants: E545K

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

Evidence Type(s): Oncogenic

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

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

Genes: 5290 5295

Variants: C420R E545K G1049R H1047L H1047R M1043I N564D

[Paragraph-level] PMCID: PMC3378484 Section: RESULTS PassageIndex: 14

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: K942Q | Summary: The K942Q mutation is associated with altered lipid binding properties, indicating a change in molecular function related to lipid interactions. Evidence Type: Functional | Mutation: R949D | Summary: The R949D mutation shows much reduced binding to anionic lipids, suggesting an alteration in molecular function related to lipid interactions.

Gene→Variant (gene-first): 5294:K942Q 5294:R949D

Genes: 5294

Variants: K942Q R949D

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

Evidence Type(s): Functional, Oncogenic

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

Gene→Variant (gene-first): 5290:D915N

Genes: 5290

Variants: D915N

[Paragraph-level] PMCID: PMC3378484 Section: RESULTS PassageIndex: 7

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: deletion of residues 1051-1068 | Summary: The deletion of residues 1051-1068 in p110alpha alters its molecular function by abrogating lipid kinase activity and lipid binding, indicating its functional importance.

Gene→Variant (gene-first): 5290:deletion of residues 1051-1068

Genes: 5290

Variants: deletion of residues 1051-1068

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

Evidence Type(s): Oncogenic, Functional

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

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

Genes: 5290

Variants: H1047R

[Paragraph-level] PMCID: PMC3378484 Section: RESULTS PassageIndex: 3

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: K942 | Summary: The mutation K942 is described as being important for p110gamma recognizing the substrate PtdIns(4,5)P2 head group, indicating that it alters molecular or biochemical function. Evidence Type: Functional | Mutation: R949 | Summary: The mutation R949 is also noted for its importance in the recognition of the substrate PtdIns(4,5)P2 head group, suggesting it alters molecular or biochemical function.

Gene→Variant (gene-first): 5294:K942 5294:R949

Genes: 5294

Variants: K942 R949

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

Evidence Type(s): Predictive, Oncogenic

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

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

Genes: 673

Variants: 1799T > A p.V600E

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

Evidence Type(s): Predictive, Functional, Oncogenic

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

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

Genes: 2322

Variants: D835 D835N/E

[Paragraph-level] PMCID: PMC4675689 Section: RESULTS PassageIndex: 7

Evidence Type(s): Predictive, Functional

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

Gene→Variant (gene-first): 2322:D835H

Genes: 2322

Variants: D835H

[Paragraph-level] PMCID: PMC4675689 Section: RESULTS PassageIndex: 6

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: D835Y | Summary: The D835Y mutation alters molecular interactions, as it is described as having large and bulky hydrophobic amino acid residues that affect hydrogen bonding and steric compatibility. Evidence Type: Functional | Mutation: D835V | Summary: The D835V mutation is characterized by large and bulky hydrophobic amino acid residues, impacting molecular interactions and steric compatibility with the protein structure.

Gene→Variant (gene-first): 2322:D835Y/V

Genes: 2322

Variants: D835Y/V

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

Evidence Type(s): Functional, Oncogenic

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

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

Genes: 2322

Variants: D835 D835E/N

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

Evidence Type(s): Predictive, Functional

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

Gene→Variant (gene-first): 2322:D835

Genes: 2322

Variants: D835

[Paragraph-level] PMCID: PMC4675689 Section: RESULTS PassageIndex: 3

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: D835 | Summary: The D835 mutation is predicted to play a critical role in stabilizing the DFG-out conformation of the kinase AL by serving as an amino-terminal capping residue for a short alpha-helix, indicating its impact on molecular function.

Gene→Variant (gene-first): 2322:D835

Genes: 2322

Variants: D835

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

Evidence Type(s): Predictive, Oncogenic

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

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

Genes: 2322

Variants: D835 D835A/E D835H D835V/Y

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

Evidence Type(s): Oncogenic

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

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

Genes: 5294 5290

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

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

Evidence Type(s): Diagnostic, Oncogenic

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

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

Genes: 5290

Variants: c.241 G>A p.E81K

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

Evidence Type(s): Oncogenic, Predisposing

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

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

Genes: 5290

Variants: c.241 G>A p.E81K

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

Evidence Type(s): Diagnostic, Oncogenic

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

Gene→Variant (gene-first): 4763:C>T

Genes: 4763

Variants: C>T

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

Evidence Type(s): Oncogenic, Predictive

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

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

Genes: 2260

Variants: p.K656E p.V561M

[Paragraph-level] PMCID: PMC8077124 Section: ABSTRACT PassageIndex: 9

Evidence Type(s): Predictive

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

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

Genes: 2260

Variants: p.K656E p.V561M

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

Evidence Type(s): Oncogenic, Predictive

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

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

Genes: 2260

Variants: p.K656E p.V561M

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

Evidence Type(s): Predictive, Prognostic, Oncogenic

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

Gene→Variant (gene-first): 2322:D835Y

Genes: 2322

Variants: D835Y

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

Evidence Type(s): Predictive, Oncogenic

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

Gene→Variant (gene-first): 2322:D835Y

Genes: 2322

Variants: D835Y

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

Evidence Type(s): Predictive

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

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

Genes: 2322

Variants: D835H D839G

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

Evidence Type(s): Oncogenic

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

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

Genes: 2322

Variants: D835Y D839G

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

Evidence Type(s): Oncogenic

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

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

Genes: 238

Variants: G1202R L1196M

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

Evidence Type(s): Predictive, Oncogenic, Functional

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

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

Genes: 673 7157

Variants: BRAFV600E p.V600E p.W110*

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

Evidence Type(s): Oncogenic

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

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

Genes: 23451

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

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

Evidence Type(s): Oncogenic

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

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

Genes: 673 330 58508

Variants: p.K601E p.Q547fs p.S321fs

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

Evidence Type(s): Predictive, Oncogenic

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

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

Genes: 7157 694

Variants: p.E46K p.Q36H

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

Evidence Type(s): Oncogenic

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

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

Genes: 7157 694

Variants: p.E46K p.Q36H

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

Evidence Type(s): Oncogenic, Predictive

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

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

Genes: 673

Variants: p.K601E

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

Evidence Type(s): Oncogenic, Diagnostic

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

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

Genes: 5290

Variants: H1047R

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

Evidence Type(s): Oncogenic

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

Gene→Variant (gene-first): 2064:V777L

Genes: 2064

Variants: V777L

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

Evidence Type(s): Oncogenic

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

Gene→Variant (gene-first): 2064:V777L

Genes: 2064

Variants: V777L

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

Evidence Type(s): Functional, Oncogenic

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

Gene→Variant (gene-first): 2064:V777L

Genes: 2064

Variants: V777L

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

Evidence Type(s): Oncogenic, Functional

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

Gene→Variant (gene-first): 2064:V777L

Genes: 2064

Variants: V777L

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

Evidence Type(s): Oncogenic

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

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

Genes: 2064

Variants: G776insYVMA V777L

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

Evidence Type(s): Oncogenic, Functional

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

Gene→Variant (gene-first): 2064:V777L

Genes: 2064

Variants: V777L

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

Evidence Type(s): Oncogenic

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

Gene→Variant (gene-first): 2064:V777L

Genes: 2064

Variants: V777L

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

Evidence Type(s): Oncogenic

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

Gene→Variant (gene-first): 2064:V777L

Genes: 2064

Variants: V777L

[Paragraph-level] PMCID: PMC10527017 Section: RESULTS PassageIndex: 6

Evidence Type(s): None

Summary: Not enough information in this passage.

Gene→Variant (gene-first): 2064:V777L

Genes: 2064

Variants: V777L

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

Evidence Type(s): Oncogenic

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

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

Genes: 5290 2064

Variants: H1047R V777L

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

Evidence Type(s): Oncogenic

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

Gene→Variant (gene-first): 2064:V777L

Genes: 2064

Variants: V777L

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

Evidence Type(s): Predictive, Oncogenic

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

Gene→Variant (gene-first): 1956:T790M

Genes: 1956

Variants: T790M

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

Evidence Type(s): Predictive, Functional

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

Gene→Variant (gene-first): 2050:V871I

Genes: 2050

Variants: V871I

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

Evidence Type(s): Functional, Oncogenic

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

Gene→Variant (gene-first): 2050:V871I

Genes: 2050

Variants: V871I

[Paragraph-level] PMCID: PMC7294133 Section: RESULTS PassageIndex: 14

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: V871I | Summary: The EPHB4-V871I variant alters molecular function by increasing the expression of target genes and enhancing the phosphorylation of the ERK1-2 pathway.

Gene→Variant (gene-first): 2050:V871I

Genes: 2050

Variants: V871I

[Paragraph-level] PMCID: PMC7294133 Section: RESULTS PassageIndex: 13

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: V871I | Summary: The V871I mutation in EPHB4 alters molecular function, as indicated by the increased number of colonies formed in the colony formation assay in soft agar compared to wild type and empty vector controls.

Gene→Variant (gene-first): 2050:V871I

Genes: 2050

Variants: V871I

[Paragraph-level] PMCID: PMC7294133 Section: RESULTS PassageIndex: 12

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: V871I | Summary: The EPHB4-V871I variant alters the migration properties of cells, indicating a change in molecular or biochemical function.

Gene→Variant (gene-first): 2050:V871I

Genes: 2050

Variants: V871I

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

Evidence Type(s): Functional, Oncogenic

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

Gene→Variant (gene-first): 2050:V871I

Genes: 2050

Variants: V871I

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

Evidence Type(s): Functional, Oncogenic

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

Gene→Variant (gene-first): 2050:V871I

Genes: 2050

Variants: V871I

[Paragraph-level] PMCID: PMC7294133 Section: RESULTS PassageIndex: 9

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: V871I | Summary: The V871I mutation alters the molecular function related to the proliferation and migration of neuroblastoma (NB) cell lines.

Gene→Variant (gene-first): 2050:V871I

Genes: 2050

Variants: V871I

[Paragraph-level] PMCID: PMC7294133 Section: RESULTS PassageIndex: 8

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: V871I | Summary: The EPHB4-V871I variant was functionally characterized, showing that it does not impair EPHB4 expression at the mRNA and protein levels.

Gene→Variant (gene-first): 2050:V871I

Genes: 2050

Variants: V871I

[Paragraph-level] PMCID: PMC7294133 Section: RESULTS PassageIndex: 5

Evidence Type(s): None

Summary: Not enough information in this passage.

Gene→Variant (gene-first): 238:F1174L 2260:N457K 238:R1275Q

Genes: 238 2260

Variants: F1174L N457K R1275Q

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

Evidence Type(s): Oncogenic

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

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

Genes: 4613 2050

Variants: A417S V871I

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

Evidence Type(s): Oncogenic

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

Gene→Variant (gene-first): 238:F1174L

Genes: 238

Variants: F1174L

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

Evidence Type(s): Diagnostic

Summary: Evidence Type: Diagnostic | Mutation: V871I | Summary: The EPHB4-V871I mutation is identified in neuroblastoma (NB) patients, suggesting its role in defining or classifying the disease.

Gene→Variant (gene-first): 2050:V871I

Genes: 2050

Variants: V871I