[Paper-level Aggregated] PMCID: PMC5792548

Evidence Type(s): Predictive

Summary: 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: Predictive Mutation: C797S | Summary: The C797S mutation is associated with resistance to osimertinib, indicating its role in therapy response.

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

Genes: EGFR(1956)

Variants: T790M C797S

[Paper-level Aggregated] PMCID: PMC5762309

Evidence Type(s): Functional

Summary: Mutation: V559D | Summary: The V559D mutation alters the molecular function of the KIT protein, affecting cell proliferation, auto-phosphorylation, and phosphorylation at specific sites. It demonstrates changes in molecular function related to treatment response and is evidenced by its selectivity and efficacy in biochemical assays and signaling pathways.

Evidence Type: Functional Mutation: L576P | Summary: The L576P mutation alters molecular or biochemical function, as indicated by its mention in binding assays.

Evidence Type: Functional Mutation: A829P | Summary: The A829P mutation alters molecular or biochemical function, as suggested by its discussion in binding assays.

Evidence Type: Functional

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

Genes: KIT(3815)

Variants: V559D L576P A829P

[Paper-level Aggregated] PMCID: PMC5762309

Evidence Type(s): Oncogenic

Summary: Mutation: V559D | Summary: The V559D mutation is associated with tumor development and progression, as it contributes to tumor growth and is identified as a primary gain-of-function mutation in Gastrointestinal Stromal Tumors (GISTs). It is linked to the proliferation of BaF3-TEL-KIT-V559D cells and shows strong binding to the inhibitor CHMFL-KIT-031, indicating its role in tumor development.

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): KIT(3815):V559D KIT(3815):L576P KIT(3815):T670I KIT(3815):V654A KIT(3815):N822K KIT(3815):D816V

Genes: KIT(3815)

Variants: V559D L576P T670I V654A N822K D816V

[Paper-level Aggregated] PMCID: PMC5762309

Evidence Type(s): Predictive

Summary: Mutation: V559D | Summary: The V559D mutation correlates with sensitivity to the KIT kinase inhibitor CHMFL-KIT-031, indicating a predictive relationship for treatment response. It is selectively inhibited by CHMFL-KIT-031, demonstrating its potential predictive value for therapy effectiveness. The mutation is associated with a dose-dependent inhibition of tumor growth, suggesting a correlation with treatment response.

Evidence Type: Predictive Mutation: L576P | Summary: The L576P mutation shows sensitivity to Imatinib, suggesting it may predict treatment response in patients with this variant.

Evidence Type: Predictive Mutation: V654A | Summary: The V654A mutation exhibits moderate sensitivity to CHMFL-KIT-031, indicating a predictive relationship for treatment response.

Evidence Type: Predictive Mutation: N822K | Summary: The N822K mutation shows similar sensitivity to Imatinib as V654A, suggesting it may predict treatment response.

Evidence Type: Predictive Mutation: D816V | Summary: The D816V mutation is resistant to both Imatinib and Sunitinib, indicating a predictive relationship for treatment resistance.

Evidence Type: Predictive Mutation: T670I | Summary: The T670I mutation is resistant to both Imatinib and Sunitinib, indicating a predictive relationship for treatment resistance.

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

Genes: KIT(3815)

Variants: V559D L576P V654A N822K D816V T670I

[Paper-level Aggregated] PMCID: PMC5652823

Evidence Type(s): Oncogenic

Summary: Mutation: T790M | Summary: The presence of the EGFR-T790M mutation contributes to tumor development and progression, particularly in the context of resistance to EGFR-TKI therapy.

Evidence Type: Oncogenic Mutation: V600E | Summary: The BRAF V600E mutation is identified as an oncogenic driver mutation contributing to tumor development and progression in patients with cancer.

Evidence Type: Oncogenic Mutation: c.2203G>A; p.G735S | Summary: The mutation c.2203G>A; p.G735S has been described in the context of lung cancer, indicating its potential role in tumor development or progression.

Evidence Type: Oncogenic Mutation: c.2258T>C; p.P753L | Summary: The mutation c.2258T>C; p.P753L is noted in the context of a patient with stage IIIA SCC, suggesting its contribution to tumor development or progression in lung cancer.

Evidence Type: Oncogenic Mutation: c.2543C>T; p.P848L | Summary: The mutation c.2543C>T; p.P848L has been previously described in lung samples, suggesting its role in tumor development or progression, thus supporting its classification as oncogenic.

Evidence Type: Oncogenic Mutation: c.2527G>A; p.V843I | Summary: The c.2527G>A; p.V843I mutation is described as activating, indicating its contribution to tumor development or progression in lung cancer.

Evidence Type: Oncogenic Mutation: c.2155G>T; p.G719C | Summary: The c.2155G>T; p.G719C mutation is an activating mutation in the EGFR gene that contributes to tumor development.

Evidence Type: Oncogenic Mutation: p.R248W | Summary: The p.R248W mutation in the TP53 gene is a common genetic variant in small-cell lung cancer that contributes to tumor development.

Gene→Variant (gene-first): EGFR(1956):T790M BRAF(673):V600E EGFR(1956):c.2203G>A EGFR(1956):p.G735S EGFR(1956):c.2258T>C EGFR(1956):p.P753L EGFR(1956):c.2543C>T EGFR(1956):p.P848L EGFR(1956):c.2527G>A EGFR(1956):p.V843I EGFR(1956):c.2155G>T EGFR(1956):p.G719C TP53(7157):p.R248W

Genes: EGFR(1956) BRAF(673) TP53(7157)

Variants: T790M V600E c.2203G>A p.G735S c.2258T>C p.P753L c.2543C>T p.P848L c.2527G>A p.V843I c.2155G>T p.G719C p.R248W

[Paper-level Aggregated] PMCID: PMC5652823

Evidence Type(s): Prognostic

Summary: Mutation: T790M | Summary: The T790M mutation may correlate with disease outcome, as indicated by the progression-free survival (PFS) and overall survival (OS) data, although specific median values have not been reached.

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

Genes: EGFR(1956)

Variants: T790M

[Paper-level Aggregated] PMCID: PMC5652823

Evidence Type(s): Predictive

Summary: Mutation: T790M | Summary: The T790M mutation is associated with response to the 3rd-generation EGFR-TKI osimertinib, indicating its predictive value for treatment sensitivity. It is also linked to acquired resistance to 1st/2nd generation EGFR-TKI therapy and correlates with treatment response, as evidenced by observed partial remissions and stable disease in patients treated with osimertinib.

Evidence Type: Predictive Mutation: c.2203G>A; p.G735S | Summary: The patient with the mutation c.2203G>A; p.G735S showed progressive disease on 2nd line EGFR-TKI therapy with gefitinib, suggesting a correlation with resistance to this specific therapy.

Evidence Type: Predictive Mutation: c.2258T>C; p.P753L | Summary: The mutation c.2258T>C; p.P753L was associated with treatment using erlotinib, indicating a potential correlation with resistance or sensitivity to this therapy.

Evidence Type: Predictive Mutation: c.2543C>T; p.P848L | Summary: The mutation c.2543C>T; p.P848L is associated with a patient's response to erlotinib, indicating its predictive value for treatment outcomes.

Evidence Type: Predictive Mutation: c.2527G>A; p.V843I | Summary: Although the c.2527G>A; p.V843I mutation is activating, it does not confer sensitivity to EGFR-TKIs, which relates to its predictive value regarding therapy response.

Evidence Type: Predictive Mutation: E709A | Summary: The E709A mutation is associated with a sensitizing driver mutation that correlates with response to targeted therapy in patients.

Evidence Type: Predictive Mutation: G719S | Summary: The G719S mutation is associated with a sensitizing driver mutation that correlates with response to targeted therapy in patients.

Gene→Variant (gene-first): EGFR(1956):T790M EGFR(1956):c.2203G>A EGFR(1956):p.G735S EGFR(1956):c.2258T>C EGFR(1956):p.P753L EGFR(1956):c.2543C>T EGFR(1956):p.P848L EGFR(1956):c.2527G>A EGFR(1956):p.V843I EGFR(1956):E709A EGFR(1956):G719S

Genes: EGFR(1956)

Variants: T790M c.2203G>A p.G735S c.2258T>C p.P753L c.2543C>T p.P848L c.2527G>A p.V843I E709A G719S

[Paper-level Aggregated] PMCID: PMC5629366

Evidence Type(s): Functional

Summary: Mutation: R132H | Summary: The R132H mutation alters the histone methylation phenotype in AML cells, demonstrating a change in molecular function related to histone trimethylation levels.

Gene→Variant (gene-first): IDH1(3417):R132H

Genes: IDH1(3417)

Variants: R132H

[Paper-level Aggregated] PMCID: PMC5629366

Evidence Type(s): Oncogenic

Summary: Mutation: R132C | Summary: The R132C mutation in IDH1 contributes to tumor development, supporting its classification as an oncogenic variant.

Evidence Type: Oncogenic Mutation: R132G | Summary: The R132G mutation in IDH1 is implicated in tumor development, supporting its classification as an oncogenic variant.

Evidence Type: Oncogenic Mutation: R132H | Summary: The R132H mutation in IDH1 is associated with tumor development or progression in human AML cells, indicating its oncogenic potential.

Evidence Type: Oncogenic Mutation: R132L | Summary: The R132L mutation in IDH1 contributes to tumor development, supporting its classification as an oncogenic variant.

Evidence Type: Oncogenic Mutation: R132S | Summary: The R132S mutation in IDH1 is implicated in tumor development, indicating its oncogenic potential.

Evidence Type: Oncogenic Mutation: p.D835del | Summary: The p.D835del mutation in FLT3-TKD is associated with tumor development in acute myeloid leukemia (AML) as indicated by its presence in primary AML cells.

Evidence Type: Oncogenic Mutation: p.Q61R | Summary: The p.Q61R mutation in NRAS is implicated in tumor progression in acute myeloid leukemia (AML) as it was identified as an additional aberration in the patient’s AML cells.

Gene→Variant (gene-first): IDH1(3417):R132C IDH1(3417):R132G IDH1(3417):R132H IDH1(3417):R132L IDH1(3417):R132S FLT3(2322):p.D835del NRAS(4893):p.Q61R

Genes: IDH1(3417) FLT3(2322) NRAS(4893)

Variants: R132C R132G R132H R132L R132S p.D835del p.Q61R

[Paper-level Aggregated] PMCID: PMC5629366

Evidence Type(s): Predictive

Summary: Mutation: R132C | Summary: The R132C mutation in IDH1 is associated with sensitivity to the IDH1 inhibitor BAY1436032, indicating a predictive relationship for therapy response.

Evidence Type: Predictive Mutation: R132G | Summary: The R132G mutation in IDH1 shows sensitivity to the IDH1 inhibitor BAY1436032, suggesting it is predictive of treatment response.

Evidence Type: Predictive Mutation: R132H | Summary: The R132H mutation in IDH1 correlates with sensitivity to the IDH1 inhibitor BAY1436032, indicating a predictive relationship for therapy response and is associated with treatment response in AML cells.

Evidence Type: Predictive Mutation: R132L | Summary: The R132L mutation in IDH1 is linked to sensitivity to the IDH1 inhibitor BAY1436032, suggesting a predictive relationship for treatment response.

Evidence Type: Predictive Mutation: R132S | Summary: The R132S mutation in IDH1 is associated with sensitivity to the IDH1 inhibitor BAY1436032, indicating a predictive relationship for therapy response.

Gene→Variant (gene-first): IDH1(3417):R132C IDH1(3417):R132G IDH1(3417):R132H IDH1(3417):R132L IDH1(3417):R132S

Genes: IDH1(3417)

Variants: R132C R132G R132H R132L R132S

[Paper-level Aggregated] PMCID: PMC5615879

Evidence Type(s): Functional

Summary: Mutation: p.K558delinsBP | Summary: The mutation p.K558delinsBP (c.1673_1674insTCC) indicates an alteration in molecular or biochemical function due to the insertion of nucleotides.

Evidence Type: Functional Mutation: Ala-Tyr | Summary: The duplication of Ala-Tyr at codons 502-503 suggests an alteration in molecular function due to the mutation.

Evidence Type: Functional Mutation: p.Y503_F504insTY | Summary: The insertion of p.Y503_F504insTY indicates a change in the molecular or biochemical function associated with the mutation.

Gene→Variant (gene-first): KIT(3815):p.K558delinsBP KIT(3815):Ala-Tyr KIT(3815):p.Y503_F504insTY

Genes: KIT(3815)

Variants: p.K558delinsBP Ala-Tyr p.Y503_F504insTY

[Paper-level Aggregated] PMCID: PMC5615879

Evidence Type(s): Oncogenic

Summary: Mutation: K558 del | Summary: The K558 del mutation is part of a common in-frame deletion associated with tumor development. Additionally, an in-frame deletion in exon 11 is linked to oncogenesis in a GIST.

Evidence Type: Oncogenic Mutation: V555del | Summary: The V555del mutation is identified as a somatic variant contributing to tumor progression.

Evidence Type: Oncogenic Mutation: c.1669_1674delTGGAAG | Summary: The c.1669_1674delTGGAAG mutation is a common in-frame deletion that plays a role in tumor development.

Evidence Type: Oncogenic Mutation: c.1676T>A | Summary: The c.1676T>A mutation is associated with oncogenic activity as a somatic variant.

Evidence Type: Oncogenic Mutation: c.1679T>A | Summary: The c.1679T>A mutation is recognized as a somatic variant that contributes to tumor progression.

Evidence Type: Oncogenic Mutation: p.V559D | Summary: The p.V559D mutation is identified as a somatic variant that plays a role in tumor development.

Evidence Type: Oncogenic Mutation: p.V560D | Summary: The p.V560D mutation is associated with oncogenic behavior as a somatic variant.

Evidence Type: Oncogenic Mutation: c.1666C>G | Summary: The mutation c.1666C>G, resulting in the p.Q556E protein change, is identified as a novel mutation in a classic hot-spot region, suggesting its contribution to tumor development. It is also associated with tumor progression as part of the KIT mutations observed in the study.

Evidence Type: Oncogenic Mutation: c.1666_1668dupCAG | Summary: The mutation c.1666_1668dupCAG, leading to the p.Q556dup protein change, is noted as a novel mutation associated with double mutations, indicating its potential role in tumor progression. It contributes to tumor development or progression, being one of the common KIT mutations identified.

Evidence Type: Oncogenic Mutation: c.1672_1677delAAGGTTinsAGT | Summary: The mutation c.1672_1677delAAGGTTinsAGT, resulting in the p.K558_V559delinsS protein change, is described as a partner mutation in double mutations, suggesting its involvement in oncogenic processes. It is implicated in tumor development or progression, being part of the KIT mutations found in the cases.

Evidence Type: Oncogenic Mutation: p.K642R | Summary: The novel substitution mutation p.K642R (c.1925A>G) is implicated in tumor progression in a GIST, supporting its oncogenic potential. It is linked to tumor development or progression, as it is part of the KIT mutations observed in the study.

Evidence Type: Oncogenic Mutation: c.1504_1509 dup GCCTAT | Summary: The mutation c.1504_1509 dup GCCTAT is associated with tumor development in cases of small intestine tumors, indicating its role in oncogenesis.

Evidence Type: Oncogenic Mutation: c.1509_1510insACCTAT | Summary: The insertion mutation c.1509_1510insACCTAT is noted in a case of duodenal GIST, contributing to tumor progression. It is associated with tumor development or progression, as it is one of the identified KIT mutations.

Evidence Type: Oncogenic Mutation: c.2466T>A; p.N822K | Summary: The mutation p.N822K (c.2466T>A) is associated with tumor development in a case of jejunal cancer, indicating its potential role in oncogenesis.

Gene→Variant (gene-first): KIT(3815):K558 del KIT(3815):V555del KIT(3815):c.1669_1674delTGGAAG KIT(3815):c.1676T>A KIT(3815):c.1679T>A KIT(3815):p.V559D KIT(3815):p.V560D POTEF(728378):c.1666C>G KIT(3815):c.1666_1668dupCAG KIT(3815):c.1672_1677delAAGGTTinsAGT POTEF(728378):p.K642R KIT(3815):c.1504_1509 dup GCCTAT KIT(3815):c.1509_1510insACCTAT KIT(3815):c.2466T>A KIT(3815):p.N822K

Genes: KIT(3815) POTEF(728378)

Variants: K558 del V555del c.1669_1674delTGGAAG c.1676T>A c.1679T>A p.V559D p.V560D c.1666C>G c.1666_1668dupCAG c.1672_1677delAAGGTTinsAGT p.K642R c.1504_1509 dup GCCTAT c.1509_1510insACCTAT c.2466T>A p.N822K

[Paper-level Aggregated] PMCID: PMC5613053

Evidence Type(s): Functional

Summary: Mutation: F691 | Summary: The F691 position is noted for its hydrophobic interaction with gilteritinib, indicating a functional alteration in the molecular interaction with the drug.

Gene→Variant (gene-first): FLT3(2322):F691

Genes: FLT3(2322)

Variants: F691

[Paper-level Aggregated] PMCID: PMC5613053

Evidence Type(s): Prognostic

Summary: Mutation: D835Y | Summary: The D835Y mutation in FLT3 is linked to poor overall survival in patients with AML, indicating its prognostic significance independent of therapy.

Evidence Type: Prognostic Mutation: F691 | Summary: The F691 mutation in FLT3 is associated with poor overall survival in AML, highlighting its prognostic implications.

Gene→Variant (gene-first): FLT3(2322):D835Y FLT3(2322):F691

Genes: FLT3(2322)

Variants: D835Y F691

[Paper-level Aggregated] PMCID: PMC5613053

Evidence Type(s): Predictive

Summary: Mutation: D835Y | Summary: The D835Y mutation in FLT3 is associated with response to the FLT3/AXL inhibitor gilteritinib, indicating its predictive value for treatment efficacy in AML. It is also associated with resistance to FLT3 inhibitors, suggesting a correlation with treatment response and sensitivity to gilteritinib.

Evidence Type: Predictive Mutation: F691 | Summary: The F691 mutation in FLT3 is associated with response to gilteritinib, indicating its predictive role in treatment outcomes for AML. It is also implicated in resistance to FLT3 inhibitors, suggesting it affects the response to gilteritinib treatment. The F691 L/I mutation is similarly associated with response to gilteritinib, while the F691 L and F691I mutations are noted for their role in resistance to FLT3 inhibitors.

Gene→Variant (gene-first): FLT3(2322):D835Y FLT3(2322):F691

Genes: FLT3(2322)

Variants: D835Y F691

[Paper-level Aggregated] PMCID: PMC5509015

Evidence Type(s): Functional

Summary: Mutation: Trp53 deletion | Summary: The functional deletion of Trp53 alters the molecular behavior of renal epithelial cells, leading to the development of cysts and dysplasia, indicating a change in cellular function associated with tumorigenesis.

Gene→Variant (gene-first): VHL(7428):Trp53 deletion

Genes: VHL(7428)

Variants: Trp53 deletion

[Paper-level Aggregated] PMCID: PMC5509015

Evidence Type(s): Oncogenic

Summary: Mutation: Trp53 deletion | Summary: The deletion of Trp53 in mice contributes to tumor development, as evidenced by the increased incidence and earlier onset of tumors in VhlDelta/DeltaTrp53Delta/DeltaRb1Delta/Delta mice compared to other genotypes.

Evidence Type: Oncogenic Mutation: A>G | Summary: The A>G mutation is associated with the development of ccRCC precursor lesions in mice, indicating its role in tumor progression.

Evidence Type: Oncogenic Mutation: C>A | Summary: The C>A mutation is part of the frequent SNVs observed in human ccRCC, suggesting its contribution to tumor development.

Evidence Type: Oncogenic Mutation: C>T | Summary: The C>T mutation is one of the most frequently occurring mutations in human ccRCC, indicating its potential role in oncogenesis.

Evidence Type: Oncogenic Mutation: G>A | Summary: The G>A mutation is included in the common classes of mutations found in human ccRCC, supporting its involvement in tumorigenesis.

Evidence Type: Oncogenic Mutation: G>T | Summary: The G>T mutation is part of the frequent SNVs in human ccRCC, suggesting its contribution to cancer development.

Evidence Type: Oncogenic Mutation: T>C | Summary: The T>C mutation is among the most frequently occurring mutations in human ccRCC, indicating its potential role in tumor progression.

Gene→Variant (gene-first): VHL(7428):Trp53 deletion VHL(7428):A>G VHL(7428):C>A VHL(7428):C>T VHL(7428):G>A VHL(7428):G>T VHL(7428):T>C

Genes: VHL(7428)

Variants: Trp53 deletion A>G C>A C>T G>A G>T T>C

[Paper-level Aggregated] PMCID: PMC5491373

Evidence Type(s): Functional

Summary: Mutation: L320S | Summary: The L320S mutation alters the molecular function of the PTEN protein by decreasing its stability, affecting its localization, and inhibiting its ability to suppress AKT phosphorylation. It also creates a new potential phosphorylation site, impacts PTEN's conformation, and alters its interaction with the membrane-bound regulatory interface, leading to increased ubiquitination.

Evidence Type: Functional Mutation: T277A | Summary: The T277A mutation alters the molecular function of the PTEN protein by decreasing its stability, impacting its localization, and inhibiting its ability to suppress AKT phosphorylation. It affects PTEN's conformation, alters its ubiquitination, and modifies the interaction between the membrane-binding regulatory interface and the C-terminal tail of PTEN.

Evidence Type: Functional Mutation: K13 | Summary: The K13 mutation is involved in blocking ubiquitination, which affects PTEN stability and its degradation process, suggesting a functional alteration.

Evidence Type: Functional Mutation: K13R | Summary: The K13R mutation blocks ubiquitination at K13, impacting PTEN stability and its biochemical function.

Evidence Type: Functional Mutation: C124S | Summary: The C124S mutation stabilizes PTEN by presumably inhibiting its enzymatic activity, indicating a change in molecular function.

Evidence Type: Functional Mutation: T366 | Summary: Phosphorylation at T366 is shown to destabilize the PTEN protein, suggesting a functional impact on its molecular behavior.

Evidence Type: Functional Mutation: S370 | Summary: Phosphorylation at S370 contributes to the destabilization of the PTEN protein, indicating a change in its molecular function.

Evidence Type: Functional Mutation: T366A | Summary: The T366A mutation is part of constructs that were tested for stability, indicating its role in altering the molecular function of PTEN.

Evidence Type: Functional Mutation: S370A | Summary: The S370A mutation is included in constructs that failed to stabilize PTEN, suggesting an impact on its molecular function.

Evidence Type: Functional Mutation: F273 | Summary: The F273 mutation is suggested to alter the molecular function of PTEN by affecting its conformation and localization.

Evidence Type: Functional Mutation: F273A | Summary: The F273A mutation shows altered inhibition on nuclear accumulation and membrane localization, indicating a change in molecular function.

Evidence Type: Functional Mutation: F273L | Summary: The F273L mutation is involved in restoring the localization of PTEN, suggesting it impacts the molecular function of the protein.

Evidence Type: Functional Mutation: L320 | Summary: The L320 mutation is implicated in maintaining PTEN conformation necessary for its localization, indicating a functional role.

Evidence Type: Functional Mutation: L320A | Summary: The introduction of L320A into PTENA4 does not affect the strong inhibition of membrane and nuclear localization, indicating a functional role in PTEN's behavior.

Evidence Type: Functional Mutation: L320D | Summary: The phospho-mimetic mutation L320D does not show instabilities similar to those seen in PTENL320S, suggesting a functional difference in protein behavior.

Evidence Type: Functional Mutation: L320E | Summary: Similar to L320D, the phospho-mimetic mutation L320E does not exhibit instabilities like PTENL320S, indicating its functional impact on PTEN.

Evidence Type: Functional Mutation: T319 | Summary: The T319 residue is involved in phosphorylation by ROCK, suggesting it plays a role in the molecular function of PTEN.

Evidence Type: Functional Mutation: T319A | Summary: The T319A mutation does not enhance protein stability, indicating an alteration in the molecular function of PTEN.

Evidence Type: Functional Mutation: T321 | Summary: The T321 residue is involved in phosphorylation by ROCK, suggesting it plays a role in the molecular function of PTEN.

Evidence Type: Functional Mutation: T321A | Summary: The T321A mutation does not enhance protein stability, indicating an alteration in the molecular function of PTEN.

Evidence Type: Functional Mutation: Lys48 | Summary: The mutation Lys48 is involved in the formation of polyubiquitin chains, and its alteration affects the molecular function related to nuclear localization of the PTENL320S variant.

Evidence Type: Functional Mutation: K48R | Summary: The K48R mutation alters the molecular function of ubiquitin, affecting the localization and abundance of PTENL320S-GFP, indicating its role in nuclear accumulation and degradation processes.

Gene→Variant (gene-first): NEDD4(4734):L320S PTEN(5728):T277A GAPDH(2597):K13 GAPDH(2597):K13R PTEN(5728):C124S PTEN(5728):T366 PTEN(5728):S370 PTEN(5728):T366A PTEN(5728):S370A PIK3R1(5295):F273 PIK3R1(5295):F273A PIK3R1(5295):F273L NEDD4(4734):L320 NEDD4(4734):L320A NEDD4(4734):L320D NEDD4(4734):L320E PTEN(5728):T319 PTEN(5728):T319A PTEN(5728):T321 PTEN(5728):T321A PTEN(5728):Lys48 PTEN(5728):K48R

Genes: NEDD4(4734) PTEN(5728) GAPDH(2597) PIK3R1(5295)

Variants: L320S T277A K13 K13R C124S T366 S370 T366A S370A F273 F273A F273L L320 L320A L320D L320E T319 T319A T321 T321A Lys48 K48R

[Paper-level Aggregated] PMCID: PMC5481739

Evidence Type(s): Functional

Summary: Mutation: V716F | Summary: The DNMT3A-V716F mutation is predicted to affect methyltransferase activity, indicating a change in molecular function associated with this variant.

Gene→Variant (gene-first): DNMT3A(1788):V716F

Genes: DNMT3A(1788)

Variants: V716F

[Paper-level Aggregated] PMCID: PMC5481739

Evidence Type(s): Oncogenic

Summary: Mutation: V716F | Summary: The somatic DNMT3A-V716F mutation is implicated in tumor development due to its association with a specific methylation signature in renal tumors.

Gene→Variant (gene-first): DNMT3A(1788):V716F

Genes: DNMT3A(1788)

Variants: V716F

[Paper-level Aggregated] PMCID: PMC5355930

Evidence Type(s): Oncogenic

Summary: Mutation: H1047R | Summary: The H1047R mutation is identified as a prevalent PIK3CA HS mutation in patients, indicating its contribution to tumor development or progression.

Evidence Type: Oncogenic Mutation: E545K | Summary: The E545K mutation is noted as one of the prevalent PIK3CA HS mutations, suggesting its role in tumor development or progression.

Evidence Type: Oncogenic Mutation: E542K | Summary: The E542K mutation is mentioned as a prevalent PIK3CA HS mutation, indicating its involvement in tumor development or progression.

Gene→Variant (gene-first): PIK3CA(5290):H1047R PIK3CA(5290):E545K PIK3CA(5290):E542K

Genes: PIK3CA(5290)

Variants: H1047R E545K E542K

[Paper-level Aggregated] PMCID: PMC5355930

Evidence Type(s): Prognostic

Summary: Mutation: E542K | Summary: The E542K mutation is associated with shorter progression-free survival (PFS) and overall survival compared to wild-type PIK3CA, indicating a potential prognostic role in disease outcome.

Evidence Type: Prognostic Mutation: E545K | Summary: The E545K mutation is associated with shorter progression-free survival (PFS) and overall survival compared to wild-type PIK3CA, indicating a potential prognostic role in disease outcome.

Gene→Variant (gene-first): PIK3CA(5290):E542K PIK3CA(5290):E545K

Genes: PIK3CA(5290)

Variants: E542K E545K

[Paper-level Aggregated] PMCID: PMC5355930

Evidence Type(s): Diagnostic

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

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

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

Gene→Variant (gene-first): PIK3CA(5290):H1047R PIK3CA(5290):E545K PIK3CA(5290):E542K

Genes: PIK3CA(5290)

Variants: H1047R E545K E542K

[Paper-level Aggregated] PMCID: PMC5355930

Evidence Type(s): Predictive

Summary: Mutation: H1047R | Summary: The H1047R mutation in PIK3CA correlates with prolonged median progression-free survival (PFS) and response to everolimus, indicating its predictive value for treatment sensitivity.

Evidence Type: Predictive Mutation: E545K | Summary: The E545K mutation in PIK3CA is associated with prolonged median progression-free survival (PFS) and response to everolimus, suggesting a predictive response to this therapy and indicating a potential predictive value regarding treatment sensitivity.

Evidence Type: Predictive Mutation: E542K | Summary: The E542K mutation in PIK3CA correlates with prolonged median progression-free survival (PFS) and response to everolimus, indicating its predictive value for treatment sensitivity and suggesting a role in resistance to hormone therapy.

Gene→Variant (gene-first): PIK3CA(5290):H1047R PIK3CA(5290):E545K PIK3CA(5290):E542K

Genes: PIK3CA(5290)

Variants: H1047R E545K E542K

[Paper-level Aggregated] PMCID: PMC5122709

Evidence Type(s): Oncogenic

Summary: Mutation: V600E | Summary: The BRAF V600E mutation is known to contribute to tumor development and progression in melanoma, classifying it as an oncogenic variant.

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): BRAF(673):V600E NA:BRAFV600E

Genes: BRAF(673) NA

Variants: V600E BRAFV600E

[Paper-level Aggregated] PMCID: PMC5122709

Evidence Type(s): Diagnostic

Summary: Mutation: V600E | Summary: The presence of the BRAF V600E mutation is used to confirm the diagnosis of melanoma, serving as a diagnostic marker for the disease.

Gene→Variant (gene-first): BRAF(673):V600E

Genes: BRAF(673)

Variants: V600E

[Paper-level Aggregated] PMCID: PMC5122709

Evidence Type(s): Predictive

Summary: Mutation: V600E | Summary: The BRAF V600E mutation is associated with treatment response to BRAF inhibitors, indicating its predictive value for therapy outcomes in melanoma patients.

Evidence Type: Predictive Mutation: BRAFV600E | Summary: The BRAFV600E mutation is associated with response to BRAF inhibitors, indicating its predictive value for treatment outcomes in metastatic melanoma.

Gene→Variant (gene-first): BRAF(673):V600E NA:BRAFV600E

Genes: BRAF(673) NA

Variants: V600E BRAFV600E

[Paper-level Aggregated] PMCID: PMC5111006

Evidence Type(s): Functional

Summary: Mutation: p.R474 | Summary: The variant p.R474 of CHEK2 shows high conservation in homologs, suggesting potential functional significance. It is involved in forming a salt bridge crucial for protein stability, indicating its role in altering molecular function.

Evidence Type: Functional Mutation: p.R474C | Summary: The mutation p.R474C disrupts the salt bridge with p.E394, leading to protein instability and poor activation in response to DNA damage. This alteration affects the molecular function of CHK2, indicating its functional importance.

Evidence Type: Functional Mutation: p.R210 | Summary: The mutation p.R210 is not well conserved and does not significantly affect the function or structure of the protein, particularly in its interaction with the immunoglobulin Fc fragment.

Evidence Type: Functional Mutation: p.R210Q | Summary: The mutation p.R210Q is not likely to affect the function and structure of the protein, indicating a focus on its molecular function.

Gene→Variant (gene-first): CHEK2(11200):p.R474 CHEK2(11200):p.R474C FCGRT(2217):p.R210 FCGRT(2217):p.R210Q

Genes: CHEK2(11200) FCGRT(2217)

Variants: p.R474 p.R474C p.R210 p.R210Q

[Paper-level Aggregated] PMCID: PMC5111006

Evidence Type(s): Oncogenic

Summary: Mutation: L858R | Summary: The L858R mutation in the EGFR gene is associated with tumor development in lung cancer, indicating its role as a somatic variant contributing to oncogenesis.

Evidence Type: Oncogenic Mutation: p.R474C | Summary: The variant p.R474C contributes to tumor development or progression by affecting the function of CHK2, a gene implicated in cell cycle regulation and DNA damage response. Additionally, the homozygous CHEK2 variant p.R474C is suggested to be contributory to familial cancer, as inactivation of CHEK2 in mice led to cancers in multiple organs.

Gene→Variant (gene-first): EGFR(1956):L858R CHEK2(11200):p.R474C

Genes: EGFR(1956) CHEK2(11200)

Variants: L858R p.R474C

[Paper-level Aggregated] PMCID: PMC5111006

Evidence Type(s): Predisposing

Summary: Mutation: rs1042522 | Summary: The variant rs1042522 (TP53, p.P72R) is associated with Li-Fraumeni syndrome, indicating a potential inherited risk for disease.

Evidence Type: Predisposing Mutation: rs169547 | Summary: The variant rs169547 (BRCA2, p.V2466A) is linked to hereditary breast/ovarian cancer, suggesting it may confer inherited risk for disease.

Gene→Variant (gene-first): TP53(7157):rs1042522 BRCA2(675):rs169547

Genes: TP53(7157) BRCA2(675)

Variants: rs1042522 rs169547

[Paper-level Aggregated] PMCID: PMC5111006

Evidence Type(s): Diagnostic

Summary: Mutation: rs757110 | Summary: The variant rs757110 in ABCC8 is associated with diabetes or insulin secretion, indicating its role in defining or classifying a disease.

Evidence Type: Diagnostic Mutation: rs5215 | Summary: The variant rs5215 in KCNJ11 is associated with diabetes or insulin secretion, indicating its role in defining or classifying a disease.

Evidence Type: Diagnostic Mutation: rs5219 | Summary: The variant rs5219 in KCNJ11 is associated with diabetes or insulin secretion, indicating its role in defining or classifying a disease.

Evidence Type: Diagnostic Mutation: rs2468844 | Summary: The variant rs2468844 in SAA2 is associated with carotid intima media thickness, indicating its role in defining or classifying a disease.

Evidence Type: Diagnostic Mutation: rs11703684 | Summary: The variant rs11703684 in PIWIL3 is associated with oligospermia, indicating its role in defining or classifying a disease.

Gene→Variant (gene-first): ABCC8(6833):rs757110 KCNJ11(3767):rs5215 KCNJ11(3767):rs5219 SAA2(6289):rs2468844 PIWIL3(440822):rs11703684

Genes: ABCC8(6833) KCNJ11(3767) SAA2(6289) PIWIL3(440822)

Variants: rs757110 rs5215 rs5219 rs2468844 rs11703684

[Paper-level Aggregated] PMCID: PMC5083195

Evidence Type(s): Functional

Summary: Mutation: rs1122269 | Summary: The variant rs1122269 showed negative correlations with the expression of CDH4 in a cis-manner, indicating it may alter molecular function related to gene expression. It also affects CDH4 expression levels in lymphoblastoid cell lines after exposure to gemcitabine, demonstrating a functional impact on molecular expression.

Evidence Type: Functional Mutation: rs4925193 | Summary: The variant rs4925193 demonstrated negative correlations with the expression of CDH4 in a cis-manner, suggesting it may influence molecular function associated with gene expression.

Gene→Variant (gene-first): CDH4(1002):rs1122269 CDH4(1002):rs4925193

Genes: CDH4(1002)

Variants: rs1122269 rs4925193

[Paper-level Aggregated] PMCID: PMC5083195

Evidence Type(s): Prognostic

Summary: Mutation: rs1122269 | Summary: The mRNA expression levels of CDH4, associated with variant rs1122269, correlated with overall survival (OS) in pancreatic cancer patients, indicating a potential prognostic role.

Evidence Type: Prognostic Mutation: rs4925193 | Summary: The mRNA expression levels of CDH4, associated with variant rs4925193, correlated with overall survival (OS) in pancreatic cancer patients, suggesting a potential prognostic significance.

Gene→Variant (gene-first): CDH4(1002):rs1122269 CDH4(1002):rs4925193

Genes: CDH4(1002)

Variants: rs1122269 rs4925193

[Paper-level Aggregated] PMCID: PMC5083195

Evidence Type(s): Predictive

Summary: Mutation: rs7515290 | Summary: The SNP rs7515290 showed trends associated with gemcitabine IC50 values, indicating a potential correlation with drug response in pancreatic cancer.

Evidence Type: Predictive Mutation: rs1374679 | Summary: The SNP rs1374679 demonstrated trends associated with gemcitabine IC50 values, suggesting a possible link to drug response in pancreatic cancer.

Evidence Type: Predictive Mutation: rs10979372 | Summary: The SNP rs10979372 was associated with gemcitabine IC50 values, indicating its potential role in influencing drug response in pancreatic cancer.

Evidence Type: Predictive Mutation: rs1122269 | Summary: The SNP rs1122269 showed trends related to gemcitabine IC50 values and correlates with the response to gemcitabine treatment, indicating its potential as a predictive biomarker for therapy response in pancreatic cancer.

Evidence Type: Predictive Mutation: rs9637468 | Summary: The variant rs9637468 is associated with gemcitabine response during pancreatic cancer therapy, indicating its potential as a genetic biomarker for predicting treatment outcomes.

Evidence Type: Predictive Mutation: rs4925193 | Summary: The variant rs4925193 is associated with gemcitabine response during pancreatic cancer therapy, suggesting its role as a genetic biomarker for predicting treatment outcomes.

Gene→Variant (gene-first): LRRC7(57554):rs7515290 NA:rs1374679 NA:rs10979372 CDH4(1002):rs1122269 NA:rs9637468 CDH4(1002):rs4925193

Genes: LRRC7(57554) NA CDH4(1002)

Variants: rs7515290 rs1374679 rs10979372 rs1122269 rs9637468 rs4925193

[Paper-level Aggregated] PMCID: PMC5029699

Evidence Type(s): Functional

Summary: Mutation: K650 | Summary: The K650 mutation alters molecular or biochemical function, with assessments indicating its impact on FGFR3 activity.

Evidence Type: Functional Mutation: K650E | Summary: The K650E mutation significantly increases auto-phosphorylation of FGFR3 KD, alters the conformation of the A-loop, and is associated with altered kinase activity, indicating a change 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: 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: N540K | Summary: The N540K mutation leads to a substantial increase in auto-phosphorylation of FGFR3 KD and is located near the ATP binding pocket, 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 and is located near the ATP binding pocket, suggesting it may alter the molecular function of FGFR3.

Evidence Type: Functional Mutation: I538 | Summary: The I538 mutation is part of the molecular brake in the FGFR3 structure, indicating it may affect molecular or biochemical function.

Evidence Type: Functional Mutation: I538V | Summary: The I538V mutation had a substantial effect on drug binding, indicating an alteration in molecular function.

Evidence Type: Functional Mutation: R669 | Summary: The R669 mutation alters molecular interactions and is associated with cancer, indicating its contribution to tumor development or progression.

Evidence Type: Functional Mutation: R669G | Summary: The R669G mutation is the most activating variant, resulting in increased auto-phosphorylation of FGFR3 KD, alters molecular interactions, and promotes an active conformation, indicating a change in molecular function.

Evidence Type: Functional Mutation: R669Q | Summary: The R669Q mutation results in increased auto-phosphorylation of FGFR3 KD, indicating an alteration in molecular function.

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: 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: Functional Mutation: G637W | Summary: The G637W mutation resulted in kinase inactivation, demonstrating an alteration in molecular function.

Evidence Type: Functional Mutation: G697C | Summary: The G697C mutation alters molecular or biochemical function, although it does not affect kinase activity directly as measured in vitro.

Evidence Type: Functional Mutation: D617G | Summary: The D617G mutation completely abolished kinase activity, indicating that it alters molecular function.

Evidence Type: Functional Mutation: V555 | Summary: The V555 mutation is associated with an increase in kinase activity, indicating an alteration in molecular function.

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: E466K | Summary: The E466K mutation is predicted to reduce protein production or completely inactivate the kinase, indicating a functional alteration.

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): FGFR3(2261):K650 FGFR3(2261):K650E FGFR3(2261):K650N FGFR3(2261):N540 FGFR3(2261):N540K FGFR3(2261):N540S FGFR2(2263):I538 FGFR2(2263):I538V FGFR3(2261):R669 FGFR3(2261):R669G FGFR3(2261):R669Q FGFR1(2260):D641 FGFR1(2260):D641G FGFR1(2260):D641N FGFR1(2260):G637W FGFR3(2261):G697C FGFR3(2261):D617G FGFR3(2261):V555 FGFR3(2261):V555M FGFR2(2263):E466K FGFR1(2260):R675G FGFR1(2260):R675 FGFR3(2261):H650 FGFR2(2263):Y653

Genes: FGFR3(2261) FGFR2(2263) FGFR1(2260)

Variants: K650 K650E K650N N540 N540K N540S I538 I538V R669 R669G R669Q D641 D641G D641N G637W G697C D617G V555 V555M E466K R675G R675 H650 Y653

[Paper-level Aggregated] PMCID: PMC5029699

Evidence Type(s): Oncogenic

Summary: Mutation: K650 | Summary: The K650 mutation in FGFR3 is identified as a frequently mutated hotspot associated with tumor development and progression, located in a hot spot within the A-loop of the FGFR3 kinase domain.

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

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, linked to a transformed phenotype and anchorage independent growth in cell lines, indicating its contribution to tumor progression.

Evidence Type: Oncogenic Mutation: R669 | Summary: The R669 mutation is situated near the A-loop of the FGFR3 kinase domain and is associated with cancer, indicating its potential role in tumor development or progression.

Evidence Type: Oncogenic Mutation: K650E | Summary: The K650E mutation is described as a highly activating variant linked to a transformed phenotype and anchorage independent growth in cell lines, suggesting its significant contribution to tumor development and progression.

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.

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: Oncogenic Mutation: R669G | Summary: The highly activating R669G mutation contributes to tumor development or progression, supporting its oncogenic potential.

Gene→Variant (gene-first): FGFR3(2261):K650 FGFR3(2261):G697 FGFR3(2261):N540 FGFR3(2261):N540K FGFR3(2261):R669 FGFR3(2261):K650E FGFR1(2260):R675G FGFR3(2261):V555M FGFR3(2261):R669G

Genes: FGFR3(2261) FGFR1(2260)

Variants: K650 G697 N540 N540K R669 K650E R675G V555M R669G

[Paper-level Aggregated] PMCID: PMC5029699

Evidence Type(s): Predictive

Summary: Mutation: V555M | Summary: The V555M mutation is associated with acquired resistance to FGFR inhibitors, significantly impacting the efficacy of AZ12908010 and AZD4547, and correlating with response to therapy, including JNJ42756493.

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 had moderate effects on the efficacy of all inhibitors, reducing the efficacy of FGFR-specific inhibitors AZD4547 and JNJ42756493, indicating a correlation with treatment response and resistance.

Evidence Type: Predictive Mutation: N540K | Summary: The N540K substitution affected the efficacy of AZD4547 and JNJ42756493 more significantly, suggesting its role in treatment sensitivity and resistance.

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

Gene→Variant (gene-first): FGFR3(2261):V555M FGFR2(2263):I538V FGFR3(2261):K650E FGFR3(2261):N540K FGFR3(2261):N540S

Genes: FGFR3(2261) FGFR2(2263)

Variants: V555M I538V K650E N540K N540S

[Paper-level Aggregated] PMCID: PMC5021039

Evidence Type(s): Predictive

Summary: Mutation: E709K | Summary: E709K is associated with moderate sensitivity to gefitinib or erlotinib, indicating its predictive value for response to these therapies.

Evidence Type: Predictive Mutation: G719X | Summary: G719X shows moderate sensitivities to gefitinib or erlotinib, suggesting it may predict response to these targeted therapies.

Evidence Type: Predictive Mutation: L858R | Summary: L858R is a common mutation that has been established to correlate with response to EGFR-tyrosine kinase inhibitors, indicating its predictive value.

Evidence Type: Predictive Mutation: L861Q | Summary: L861Q demonstrates moderate sensitivities to gefitinib or erlotinib, indicating its predictive value for response to these therapies.

Evidence Type: Predictive Mutation: S768I | Summary: S768I is associated with moderate sensitivities to gefitinib or erlotinib, suggesting it may predict response to these targeted therapies.

Gene→Variant (gene-first): EGFR(1956):E709K EGFR(1956):G719X EGFR(1956):L858R EGFR(1956):L861Q EGFR(1956):S768I

Genes: EGFR(1956)

Variants: E709K G719X L858R L861Q S768I

[Paper-level Aggregated] PMCID: PMC5019182

Evidence Type(s): Functional

Summary: Mutation: p.Ala1035Thr | Summary: The p.Ala1035Thr mutation has been demonstrated to alter molecular function through a gain-of-function mechanism.

Evidence Type: Functional Mutation: p.Ala1035Val | Summary: The p.Ala1035Val mutation has been demonstrated to alter molecular function through a gain-of-function mechanism.

Gene→Variant (gene-first): PIK3CA(5290):p.Ala1035Thr PIK3CA(5290):p.Ala1035Val

Genes: PIK3CA(5290)

Variants: p.Ala1035Thr p.Ala1035Val

[Paper-level Aggregated] PMCID: PMC5019182

Evidence Type(s): Oncogenic

Summary: Mutation: p.Glu545Lys | Summary: The p.Glu545Lys mutation is identified as an oncogenic mutation contributing to tumor development or progression, associated with a gain-of-function mechanism and noted as a hotspot mutation in cancer, as indicated by its presence in the Catalogue of Somatic Mutations in Cancer (COSMIC).

Evidence Type: Oncogenic Mutation: p.His1047Arg | Summary: The p.His1047Arg mutation is classified as an oncogenic mutation, described as a low-level mosaic variant associated with features of CLOVES syndrome, contributing to tumor development or progression, supported by its identification in the Catalogue of Somatic Mutations in Cancer (COSMIC).

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

Evidence Type: Oncogenic Mutation: p.Asn345Thr | Summary: The p.Asn345Thr mutation is associated with a gain-of-function mechanism and contributes to tumor development.

Evidence Type: Oncogenic Mutation: p.Glu545Asp | Summary: The p.Glu545Asp mutation is associated with a gain-of-function mechanism and contributes to tumor development.

Evidence Type: Oncogenic Mutation: p.Gln546His | Summary: The p.Gln546His mutation is associated with a gain-of-function mechanism and contributes to tumor development.

Evidence Type: Oncogenic Mutation: p.Asn345Lys | Summary: The p.Asn345Lys mutation is associated with a gain-of-function mechanism and contributes to tumor development.

Evidence Type: Oncogenic Mutation: p.Glu545Gly | Summary: The p.Glu545Gly mutation is associated with a gain-of-function mechanism and contributes to tumor development.

Evidence Type: Oncogenic Mutation: p.Gln546Lys | Summary: The p.Gln546Lys mutation is associated with a gain-of-function mechanism and contributes to tumor development.

Evidence Type: Oncogenic Mutation: p.Gln546Pro | Summary: The p.Gln546Pro mutation is associated with a gain-of-function mechanism and contributes to tumor development.

Evidence Type: Oncogenic Mutation: p.Tyr1021His | Summary: The p.Tyr1021His mutation is associated with a gain-of-function mechanism and contributes to tumor development.

Evidence Type: Oncogenic Mutation: p.Glu726Lys | Summary: The p.Glu726Lys mutation in PIK3CA is implicated in tumor development and progression, contributing to the oncogenic characteristics observed in patients with MCAP.

Evidence Type: Oncogenic Mutation: p.Gly106Val | Summary: The p.Gly106Val mutation was found in a patient with congenital onset somatic overgrowth and other features, indicating its potential contribution to tumor development or progression.

Evidence Type: Oncogenic Mutation: p.Cys378Tyr | Summary: The p.Cys378Tyr mutation was described as a mosaic variant in a patient with hemihypertrophy and capillary malformations, suggesting its involvement in tumor development or progression.

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

Evidence Type: Oncogenic Mutation: p.Gly914Arg | Summary: The p.Gly914Arg mutation is linked to congenital overgrowth conditions, suggesting its contribution to tumor development or progression in affected individuals.

Evidence Type: Oncogenic Mutation: p.Glu542Lys | Summary: The p.Glu542Lys mutation is identified as a hotspot mutation commonly seen in cancer, indicating its contribution to tumor development or progression.

Gene→Variant (gene-first): PIK3CA(5290):p.Glu545Lys PIK3CA(5290):p.His1047Arg PIK3CA(5290):p.Arg93Gln PIK3CA(5290):p.Asn345Thr PIK3CA(5290):p.Glu545Asp PIK3CA(5290):p.Gln546His PIK3CA(5290):p.Asn345Lys PIK3CA(5290):p.Glu545Gly PIK3CA(5290):p.Gln546Lys PIK3CA(5290):p.Gln546Pro TSC2(7249):p.Tyr1021His PIK3CA(5290):p.Glu726Lys PIK3CA(5290):p.Gly106Val PIK3CA(5290):p.Cys378Tyr PIK3CA(5290):p.Glu453Lys PIK3CA(5290):p.Gly914Arg PIK3CA(5290):p.Glu542Lys

Genes: PIK3CA(5290) TSC2(7249)

Variants: p.Glu545Lys p.His1047Arg p.Arg93Gln p.Asn345Thr p.Glu545Asp p.Gln546His p.Asn345Lys p.Glu545Gly p.Gln546Lys p.Gln546Pro p.Tyr1021His p.Glu726Lys p.Gly106Val p.Cys378Tyr p.Glu453Lys p.Gly914Arg p.Glu542Lys

[Paper-level Aggregated] PMCID: PMC5019182

Evidence Type(s): Predisposing

Summary: Mutation: p.Glu726Lys | Summary: The presence of the p.Glu726Lys mutation in patients indicates a potential inherited risk for developing MCAP and its associated features.

Gene→Variant (gene-first): PIK3CA(5290):p.Glu726Lys

Genes: PIK3CA(5290)

Variants: p.Glu726Lys

[Paper-level Aggregated] PMCID: PMC5019182

Evidence Type(s): Diagnostic

Summary: Mutation: p.Glu542Lys | Summary: The p.Glu542Lys mutation is associated with developmental pediatric disorders, indicating its role in defining or classifying a disease subtype.

Evidence Type: Diagnostic Mutation: p.Glu545Lys | Summary: The p.Glu545Lys mutation is frequently observed in pediatric disorders, supporting its use in defining or classifying a disease subtype.

Evidence Type: Diagnostic Mutation: p.His1047Arg | Summary: The p.His1047Arg mutation is highly recurrent in developmental pediatric disorders, suggesting its role in defining or classifying a disease subtype.

Evidence Type: Diagnostic Mutation: p.Glu726Lys | Summary: The p.Glu726Lys mutation is associated with classic features of MCAP, which helps in defining and classifying the disease.

Gene→Variant (gene-first): PIK3CA(5290):p.Glu542Lys PIK3CA(5290):p.Glu545Lys PIK3CA(5290):p.His1047Arg PIK3CA(5290):p.Glu726Lys

Genes: PIK3CA(5290)

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

[Paper-level Aggregated] PMCID: PMC5002925

Evidence Type(s): Functional

Summary: Mutation: p.N581S | Summary: The BRAF p.N581S mutation was verified and its biological effect was predicted using algorithms, indicating that it alters molecular or biochemical function.

Evidence Type: Functional Mutation: p.L755S | Summary: The ERBB2 p.L755S mutation is described in the context of its biological significance, indicating an alteration in molecular function.

Gene→Variant (gene-first): BRAF(673):p.N581S ERBB2(2064):p.L755S

Genes: BRAF(673) ERBB2(2064)

Variants: p.N581S p.L755S

[Paper-level Aggregated] PMCID: PMC5002925

Evidence Type(s): Oncogenic

Summary: Mutation: c.4285delC (p.Gln1429fs/p.Q1429fs) | Summary: The APC c.4285delC (p.Q1429fs) mutation is identified as a heterozygous somatic variant that contributes to tumor development or progression in the context of rectal adenocarcinoma, as it was detected in tumor samples.

Evidence Type: Oncogenic Mutation: c.1742A>G (p.Asn581Ser/p.N581S) | Summary: The BRAF c.1742A>G (p.N581S) mutation is a heterozygous somatic variant that is implicated in tumor development or progression in the patient's rectal adenocarcinoma, as evidenced by its detection in tumor samples.

Evidence Type: Oncogenic Mutation: c.2264T>C (p.Leu755Ser/p.L755S) | Summary: The ERBB2 c.2264T>C (p.L755S) mutation is a heterozygous somatic variant that likely contributes to tumor development or progression, as indicated by its classification as an activating mutation and its presence in tumor samples.

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

Genes: NA

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

[Paper-level Aggregated] PMCID: PMC5002925

Evidence Type(s): Predictive

Summary: Mutation: p.L755S | Summary: The ERBB2 p.L755S mutation was used to guide treatment with trastuzumab, indicating a correlation with therapy response.

Evidence Type: Predictive

Gene→Variant (gene-first): ERBB2(2064):p.L755S

Genes: ERBB2(2064)

Variants: p.L755S

[Paper-level Aggregated] PMCID: PMC4999563

Evidence Type(s): Oncogenic

Summary: Mutation: V600E | Summary: The BRAF V600E mutation is known to contribute to tumor development and progression, supporting its classification as an oncogenic variant.

Gene→Variant (gene-first): BRAF(673):V600E

Genes: BRAF(673)

Variants: V600E

[Paper-level Aggregated] PMCID: PMC4999563

Evidence Type(s): Prognostic

Summary: Mutation: G12C | Summary: The KRAS G12C mutation is associated with inferior progression-free and overall survival in metastatic colorectal cancer (mCRC) patients compared to those with non-mutated tumors. It correlates with a median overall survival (OS) of 16.8 months, indicating a negative prognostic effect.

Evidence Type: Prognostic Mutation: G13D | Summary: The KRAS G13D mutation is associated with inferior progression-free and overall survival in mCRC patients compared to those with non-mutated tumors. It shows a median progression-free survival (PFS) of 8.8 months and a trend towards inferior overall survival (OS), suggesting potential negative prognostic implications.

Evidence Type: Prognostic Mutation: G12D | Summary: The KRAS G12D variant shows a median PFS of 10.5 months and a median overall survival (OS) of 25.2 months, suggesting its impact on disease outcome, but did not show a significant impact on overall survival, indicating it may not have a strong prognostic role.

Evidence Type: Prognostic Mutation: G12V | Summary: The KRAS G12V variant did not demonstrate a significant impact on overall survival (OS) and had a negative prognostic effect on progression-free survival (PFS) in the multivariate analysis, suggesting limited prognostic value.

Gene→Variant (gene-first): KRAS(3845):G12C KRAS(3845):G13D KRAS(3845):G12D KRAS(3845):G12V

Genes: KRAS(3845)

Variants: G12C G13D G12D G12V

[Paper-level Aggregated] PMCID: PMC4999563

Evidence Type(s): Diagnostic

Summary: Mutation: V600E | Summary: The presence of the BRAF V600E mutation is used to classify and confirm the subtype of tumors in which it is found, indicating its diagnostic relevance.

Gene→Variant (gene-first): BRAF(673):V600E

Genes: BRAF(673)

Variants: V600E

[Paper-level Aggregated] PMCID: PMC4899144

Evidence Type(s): Functional

Summary: Mutation: Y641F | Summary: The Y641F mutation alters molecular function by affecting global levels of H3K27me3, enzymatic activity, and gene expression regulation in B-cells and melanoma cells. It is associated with a gain-of-function effect, increased apoptotic resistance, and a global redistribution of H3K27me3 marks across the genome. The mutation also alters the expression of numerous transcripts and affects the distribution of H3K27me3 at promoter regions.

Evidence Type: Functional Mutation: Y646F | Summary: The Y646F mutation is described as equivalent to the Y641F mutation, suggesting it alters molecular function, although specific functional data is limited. It affects the molecular function of Ezh2 and exhibits in vitro activity against the JQEZ5 inhibitor, indicating a correlation with treatment response.

Gene→Variant (gene-first): EZH2(2146):Y641F EZH2(2146):Y646F

Genes: EZH2(2146)

Variants: Y641F Y646F

[Paper-level Aggregated] PMCID: PMC4899144

Evidence Type(s): Oncogenic

Summary: Mutation: Y641F | Summary: The Y641F mutation in EZH2 contributes to tumor development in B-cell lymphomas and melanoma, as it induces highly penetrant B-cell lymphoma in mice, is associated with splenomegaly and lymphadenopathy, and affects gene expression regulated by PRC2. It is equivalent to a common EZH2 missense mutation found in human cancers, indicating its role in malignancy and tumor progression. The mutation alters the epigenetic landscape by affecting H3K27me3 distribution and is implicated in tumor initiation and maintenance.

Evidence Type: Oncogenic Mutation: Y646F | Summary: The Y646F mutation in EZH2 is associated with tumor development and progression in melanoma, and is noted as one of the most common EZH2 missense mutations in human cancers. It is suggested to alter molecular function, although specific functional data is limited.

Evidence Type: Oncogenic Mutation: B-RAFV600E | Summary: The B-RAFV600E mutation is implicated in the majority of human melanomas, contributing to tumor development and progression through RAF/MEK/ERK activation. It is associated with oncogene-induced senescence and cooperates with the Ezh2Y641F mutation to accelerate tumorigenesis in melanoma.

Gene→Variant (gene-first): EZH2(2146):Y641F EZH2(2146):Y646F BRAF(673):B-RAFV600E

Genes: EZH2(2146) BRAF(673)

Variants: Y641F Y646F B-RAFV600E

[Paper-level Aggregated] PMCID: PMC4899144

Evidence Type(s): Prognostic

Summary: Mutation: Y641F | Summary: The presence of the Ezh2Y641F mutation correlates with a median survival of one year in tumor-bearing mice, indicating its association with disease outcome.

Gene→Variant (gene-first): EZH2(2146):Y641F

Genes: EZH2(2146)

Variants: Y641F

[Paper-level Aggregated] PMCID: PMC4899144

Evidence Type(s): Predictive

Summary: Mutation: Y641F | Summary: The Y641F mutation in Ezh2 is associated with increased sensitivity to the EZH2 inhibitor JQEZ5, indicating a correlation with treatment response and predictive value for treatment efficacy in B-cell lymphoma and melanoma models.

Evidence Type: Predictive Mutation: Y646F | Summary: The Y646F mutation exhibits in vitro activity against the JQEZ5 inhibitor, suggesting a correlation with treatment response.

Gene→Variant (gene-first): EZH2(2146):Y641F EZH2(2146):Y646F

Genes: EZH2(2146)

Variants: Y641F Y646F

[Paper-level Aggregated] PMCID: PMC4884999

Evidence Type(s): Oncogenic

Summary: Mutation: G12C | Summary: The G12C mutation in KRAS is identified as a common mutation occurring in codon 12, which contributes to tumor development or progression in lung cancer.

Gene→Variant (gene-first): KRAS(3845):G12C

Genes: KRAS(3845)

Variants: G12C

[Paper-level Aggregated] PMCID: PMC4868698

Evidence Type(s): Functional

Summary: Mutation: E483D | Summary: The JAK1E483D mutation is part of a study evaluating the transformation ability of JAK1 mutations, indicating a potential alteration in molecular function.

Evidence Type: Functional Mutation: S703I | Summary: The JAK1S703I mutation alters the molecular function by activating the JAK-STAT signaling pathway and driving cell proliferation in vitro, contributing to tumor development by enabling continual proliferation in the absence of IL-3.

Gene→Variant (gene-first): JAK1(3716):E483D JAK1(3716):S703I

Genes: JAK1(3716)

Variants: E483D S703I

[Paper-level Aggregated] PMCID: PMC4868698

Evidence Type(s): Oncogenic

Summary: Mutation: S703I | Summary: The JAK1S703I mutation is identified as an activating mutation contributing to tumor development in HCC patients. It is associated with elevated expression levels of phosphorylated JAK1 and STAT proteins, suggesting its role in tumor progression. The mutation is capable of continual proliferation in the absence of IL-3 and is present in a patient-derived xenograft (PDX) model, indicating its critical role in tumorigenesis. Additionally, it activates the JAK-STAT signaling pathway, driving cell proliferation in vitro.

Evidence Type: Oncogenic Mutation: A1086S | Summary: The A1086S mutation is located in the catalytic kinase domain of JAK1, suggesting its role in tumor development.

Evidence Type: Oncogenic Mutation: N451S | Summary: The N451S mutation is found in the SH2 domain of JAK1, indicating its potential contribution to tumor progression.

Evidence Type: Oncogenic Mutation: E483D | Summary: The E483D mutation, located in the SH2 domain of JAK1, may play a role in tumor development. It is part of a study exploring biological functions in the JAK-STAT signaling pathway, indicating its potential role in tumor development.

Evidence Type: Oncogenic Mutation: S729C | Summary: The JAK1S729C mutation is described as a known and recurrent activating mutation, indicating its role in tumor development. It serves as a positive control in studies, suggesting it contributes to continual proliferation and tumor progression.

Gene→Variant (gene-first): JAK1(3716):S703I JAK1(3716):A1086S POTEF(728378):N451S JAK1(3716):E483D JAK1(3716):S729C

Genes: JAK1(3716) POTEF(728378)

Variants: S703I A1086S N451S E483D S729C

[Paper-level Aggregated] PMCID: PMC4868698

Evidence Type(s): Predictive

Summary: Mutation: S703I | Summary: The S703I mutation in JAK1 correlates with sensitivity to the JAK1/2 inhibitor ruxolitinib and is associated with a response to this therapy, indicating its potential predictive value for treatment outcomes and therapy sensitivity.

Gene→Variant (gene-first): JAK1(3716):S703I

Genes: JAK1(3716)

Variants: S703I

[Paper-level Aggregated] PMCID: PMC4845427

Evidence Type(s): Predisposing

Summary: Mutation: A to I | Summary: The RUNX1 alterations are germline, suggesting they confer inherited risk for disease in the identified pedigrees.

Gene→Variant (gene-first): RUNX1(861):A to I

Genes: RUNX1(861)

Variants: A to I

[Paper-level Aggregated] PMCID: PMC4823825

Evidence Type(s): Functional

Summary: Mutation: K27M | Summary: The K27M mutation alters the molecular function of histone proteins, specifically in the context of histone 3 variants, impacting chromatin regulation and contributing to tumorigenesis.

Evidence Type: Functional Mutation: H1047R | Summary: The H1047R mutation affects the catalytic domain of PIK3CA, indicating an alteration in molecular or biochemical function related to the PI3K pathway.

Gene→Variant (gene-first): H3C2(8358):K27M PIK3CA(5290):H1047R

Genes: H3C2(8358) PIK3CA(5290)

Variants: K27M H1047R

[Paper-level Aggregated] PMCID: PMC4823825

Evidence Type(s): Oncogenic

Summary: Mutation: K27M | Summary: The K27M mutation is associated with tumorigenesis in Diffuse Intrinsic Pontine Gliomas (DIPGs) and high-grade gliomas (HGG), contributing to tumor development and progression in a majority of analyzed DIPG samples.

Evidence Type: Oncogenic Mutation: H1047R | Summary: The PIK3CA H1047R mutation is described as an activating mutation that contributes to tumor development and progression, particularly in high-grade astrocytoma (WHO IV).

Gene→Variant (gene-first): H3C2(8358):K27M PIK3CA(5290):H1047R

Genes: H3C2(8358) PIK3CA(5290)

Variants: K27M H1047R

[Paper-level Aggregated] PMCID: PMC4823091

Evidence Type(s): Functional

Summary: Mutation: V855A | Summary: The V855A mutation alters the molecular function of the HER3 protein, affecting its phosphorylation levels, growth response, and colony formation ability in various cellular contexts. It enhances the interaction with HER2 and trans-phosphorylation, indicating significant changes in molecular or biochemical function. Additionally, in silico modeling suggests alterations in the kinase domain and carboxyl-terminal end of the HER3 protein.

Evidence Type: Functional Mutation: L858 | Summary: The L858 mutation is part of a conserved sequence motif that stabilizes the inactive position of the alphaC helix, indicating potential functional relevance.

Evidence Type: Functional Mutation: L597V | Summary: The L597V mutation is associated with increased ERK activation, indicating a functional alteration in molecular activity.

Gene→Variant (gene-first): APC(324):V855A EGFR(1956):L858 BRAF(673):L597V

Genes: APC(324) EGFR(1956) BRAF(673)

Variants: V855A L858 L597V

[Paper-level Aggregated] PMCID: PMC4823091

Evidence Type(s): Oncogenic

Summary: Mutation: T-to-C | Summary: The T-to-C mutation in the HER3 gene is identified as a somatic variant that contributes to tumor development, as it was detected in the tumor sample but not in the patient's peripheral blood DNA.

Evidence Type: Oncogenic Mutation: V855A | Summary: The HER3-V855A mutation is implicated in tumor development and progression, contributing to oncogenic transformation and tumorigenesis, particularly in combination with HER2. It enhances growth response, promotes IL-3-independent growth, and increases colony formation capabilities in the presence of specific ligands, indicating its role in cancer signaling pathways. The mutation is associated with transforming activity and may correlate with a malignant phenotype, particularly in non-small cell lung cancer (NSCLC), where it enhances ligand-induced transformation in cell lines.

Evidence Type: Oncogenic Mutation: L858R | Summary: The L858R missense mutation is classified as an activating mutation that contributes to tumor development in the context of EGFR-related cancers.

Evidence Type: Oncogenic Mutation: L597V | Summary: The L597V mutation is classified as an intermediate kinase active variant that significantly increases BRAF activity, contributing to tumor development.

Gene→Variant (gene-first): ERBB3(2065):T-to-C APC(324):V855A EGFR(1956):L858R BRAF(673):L597V

Genes: ERBB3(2065) APC(324) EGFR(1956) BRAF(673)

Variants: T-to-C V855A L858R L597V

[Paper-level Aggregated] PMCID: PMC4823091

Evidence Type(s): Predictive

Summary: Mutation: L858R | Summary: The L858R mutation in EGFR is associated with increased sensitivity to EGFR TKIs, indicating its predictive value for therapy response.

Evidence Type: Predictive Mutation: V855A | Summary: The HER3-V855A mutation is associated with differential response to HER inhibitors and may predict response to targeted therapy, as indicated by varying sensitivity to inhibitors and its relevance in predicting response to targeted therapies in NSCLC.

Gene→Variant (gene-first): EGFR(1956):L858R APC(324):V855A

Genes: EGFR(1956) APC(324)

Variants: L858R V855A

[Paper-level Aggregated] PMCID: PMC4821611

Evidence Type(s): Oncogenic

Summary: Mutation: p.C1156Y | Summary: The mutation p.C1156Y contributes to tumor development or progression, as it is found in a significant percentage of RNA-seq reads in patient #1 and was detected in post-treatment tumor samples, particularly in the context of crizotinib resistance.

Evidence Type: Oncogenic Mutation: p.G1269A | Summary: The mutation p.G1269A is present in 100% of the RNA-seq reads in patient #3 and was also found in post-treatment tumor samples, indicating its role in tumor development or progression related to crizotinib resistance.

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

Genes: ALK(238)

Variants: p.C1156Y p.G1269A

[Paper-level Aggregated] PMCID: PMC4821611

Evidence Type(s): Predictive

Summary: Mutation: p.C1156Y | Summary: The mutation p.C1156Y in the ALK gene has been reported to confer resistance against crizotinib, indicating a correlation with treatment response.

Evidence Type: Predictive Mutation: p.G1269A | Summary: No supporting paragraph-level outputs for this evidence type.

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

Genes: ALK(238)

Variants: p.C1156Y p.G1269A

[Paper-level Aggregated] PMCID: PMC4748120

Evidence Type(s): Functional

Summary: Mutation: K-RasG12D | Summary: The K-RasG12D mutation alters the growth response of myeloid progenitors to GM-CSF, exhibits resistance to GAP stimulation, and is associated with increased levels of Ras-GTP, pERK, and pAkt in Ba/F3 cells under serum deprivation, indicating multiple changes in molecular function related to signaling pathways and colony formation.

Evidence Type: Functional Mutation: A66dup | Summary: The A66dup mutation in K-Ras sensitizes myeloid progenitors to GM-CSF, alters molecular function by increasing levels of Ras-GTP in Ba/F3 cells under serum deprivation, reduces intrinsic GTP hydrolysis rates, and impairs PI3 kinase binding, demonstrating its impact on biochemical activity.

Evidence Type: Functional Mutation: Glutamine 61; Q61 | Summary: The Glutamine 61 (Q61) mutation may alter molecular function due to structural changes from switch 2 insertions, affecting protein-protein interactions and the GTP conformation of Ras.

Evidence Type: Functional Mutation: Y64G | Summary: The Y64G mutation in K-Ras, when combined with K-RasG12D, results in significantly reduced binding to FLAG-p110alpha, indicating an alteration in molecular function.

Gene→Variant (gene-first): KRAS(3845):K-RasG12D PIK3R1(5295):A66dup KRAS(3845):Glutamine 61 KRAS(3845):Q61 PIK3CA(5290):Y64G

Genes: KRAS(3845) PIK3R1(5295) PIK3CA(5290)

Variants: K-RasG12D A66dup Glutamine 61 Q61 Y64G

[Paper-level Aggregated] PMCID: PMC4748120

Evidence Type(s): Oncogenic

Summary: Mutation: c.178_198dup | Summary: The c.178_198dup variant is a partial duplication of the switch 2 domain of K-Ras, which is associated with juvenile myelomonocytic leukaemia (JMML) and contributes to tumor development.

Evidence Type: Oncogenic Mutation: c.184_198dup | Summary: The c.184_198dup variant is a tandem duplication found in lung adenocarcinomas and colorectal cancer, indicating its role in tumor progression.

Evidence Type: Oncogenic Mutation: K-RasG12D | Summary: The K-RasG12D mutation contributes to tumor development by promoting cytokine-independent growth in Ba/F3 cells and hematopoietic progenitor cells, and is associated with elevated signaling pathways indicative of oncogenic activity.

Evidence Type: Oncogenic Mutation: A66dup | Summary: The A66dup mutation in K-Ras is associated with tumor development and progression, as it transforms the growth of primary myeloid progenitors and Ba/F3 cells, indicating its oncogenic potential.

Gene→Variant (gene-first): KRAS(3845):c.178_198dup KRAS(3845):c.184_198dup KRAS(3845):K-RasG12D PIK3R1(5295):A66dup

Genes: KRAS(3845) PIK3R1(5295)

Variants: c.178_198dup c.184_198dup K-RasG12D A66dup

[Paper-level Aggregated] PMCID: PMC4748120

Evidence Type(s): Diagnostic

Summary: Mutation: A66dup | Summary: The presence of the A66dup mutation in K-Ras has diagnostic implications, as it is associated with an atypical myeloproliferative neoplasm in the patient described.

Gene→Variant (gene-first): PIK3R1(5295):A66dup

Genes: PIK3R1(5295)

Variants: A66dup

[Paper-level Aggregated] PMCID: PMC4748120

Evidence Type(s): Predictive

Summary: Mutation: K-RasG12D | Summary: The sensitivity of Ba/F3 cells expressing K-RasG12D to MEK inhibition suggests that this mutation correlates with response to specific therapies, indicating predictive value.

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

Genes: KRAS(3845)

Variants: K-RasG12D

[Paper-level Aggregated] PMCID: PMC4741605

Evidence Type(s): Oncogenic

Summary: 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. It is part of a clone that is monitored during disease progression, and its increase in frequency at relapse suggests a correlation with tumor behavior and disease outcome independent of therapy.

Evidence Type: Oncogenic Mutation: D839G | Summary: The D839G mutation is part of the small TKD mutated clones observed in the patient, suggesting its role in tumor development or progression.

Gene→Variant (gene-first): FLT3(2322):D835Y FLT3(2322):D839G

Genes: FLT3(2322)

Variants: D835Y D839G

[Paper-level Aggregated] PMCID: PMC4741605

Evidence Type(s): Prognostic

Summary: 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.

Gene→Variant (gene-first): FLT3(2322):D835Y

Genes: FLT3(2322)

Variants: D835Y

[Paper-level Aggregated] PMCID: PMC4741605

Evidence Type(s): Predictive

Summary: 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 linked to resistance to Sorafenib treatment, suggesting it has predictive implications for therapy response.

Evidence Type: Predictive Mutation: D835Y | Summary: The D835Y mutation is associated with the patient's response to chemotherapy treatment and was successfully inhibited by treatment, indicating its relevance in predicting treatment outcomes.

Gene→Variant (gene-first): FLT3(2322):D835H FLT3(2322):D839G FLT3(2322):D835Y

Genes: FLT3(2322)

Variants: D835H D839G D835Y

[Paper-level Aggregated] PMCID: PMC4695055

Evidence Type(s): Functional

Summary: Mutation: p.982_1028del47 | Summary: The mutation p.982_1028del47 is associated with the detection of a METex14del transcript, indicating a potential alteration in molecular function related to the MET gene.

Gene→Variant (gene-first): NTRK3(4916):p.982_1028del47

Genes: NTRK3(4916)

Variants: p.982_1028del47

[Paper-level Aggregated] PMCID: PMC4695055

Evidence Type(s): Oncogenic

Summary: Mutation: p.982_1028del47 | Summary: The presence of the METex14del mutation (p.982_1028del47) suggests a contribution to tumor development or progression, as it is being screened in a cohort of cancer patients.

Evidence Type: Oncogenic Mutation: T790M | Summary: The T790M mutation is associated with tumor development in the context of non-small cell lung cancer (NSCLC) patients, indicating its role as a somatic variant contributing to cancer progression.

Evidence Type: Oncogenic Mutation: V600E | Summary: The V600E mutation in BRAF is implicated in tumor development, as it was detected in colon cancer cases, suggesting its role as a somatic variant contributing to cancer progression.

Gene→Variant (gene-first): NTRK3(4916):p.982_1028del47 EGFR(1956):T790M BRAF(673):V600E

Genes: NTRK3(4916) EGFR(1956) BRAF(673)

Variants: p.982_1028del47 T790M V600E

[Paper-level Aggregated] PMCID: PMC4675689

Evidence Type(s): Functional

Summary: Mutation: D835 | Summary: The D835 mutation is critical for stabilizing the inactive conformation of FLT3, impacting molecular interactions necessary for type II inhibitor binding. It plays a role in stabilizing the DFG-out conformation of the kinase and affects the short alpha-helix coupled to the drug-binding site.

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 and preserving critical structural features necessary for the binding of type II inhibitors.

Evidence Type: Functional Mutation: D835Y | Summary: The D835Y mutation alters molecular interactions due to large and bulky hydrophobic amino acid residues, affecting 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.

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.

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.

Gene→Variant (gene-first): FLT3(2322):D835 FLT3(2322):D835E/N NA:D835Y NA:D835V FLT3(2322):D835H FLT3(2322):D835N/E

Genes: FLT3(2322) NA

Variants: D835 D835E/N D835Y D835V D835H D835N/E

[Paper-level Aggregated] PMCID: PMC4675689

Evidence Type(s): Oncogenic

Summary: Mutation: D835 | Summary: The D835 mutation contributes to tumor development by influencing the kinase's conformation and resistance to inhibitors.

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: Oncogenic Mutation: D835H | Summary: The D835H mutation has been observed in clinical resistance to sorafenib, suggesting its role in tumor progression.

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.

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.

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): FLT3(2322):D835 NA:D835V/Y/F FLT3(2322):D835H NA:D835A/E/G/N FLT3(2322):D835E/N FLT3(2322):D835N/E

Genes: FLT3(2322) NA

Variants: D835 D835V/Y/F D835H D835A/E/G/N D835E/N D835N/E

[Paper-level Aggregated] PMCID: PMC4675689

Evidence Type(s): Predictive

Summary: Mutation: D835 | Summary: The D835 mutation is associated with resistance to FLT3 tyrosine kinase inhibitors (TKIs) and type II inhibitors, indicating its predictive value for therapy response.

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: Predictive Mutation: D835H | Summary: The D835H mutation is associated with intermediate resistance to sorafenib and type II inhibitors, indicating its predictive value for therapy response.

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: Predictive Mutation: D835N/E | Summary: The D835N/E mutations may retain sensitivity to type II FLT3 TKIs, indicating a potential response to therapy.

Gene→Variant (gene-first): FLT3(2322):D835 NA:D835V/Y/F FLT3(2322):D835H NA:D835A/E/G/N FLT3(2322):D835N/E

Genes: FLT3(2322) NA

Variants: D835 D835V/Y/F D835H D835A/E/G/N D835N/E

[Paper-level Aggregated] PMCID: PMC4654747

Evidence Type(s): Functional

Summary: Mutation: K27M | Summary: The K27M mutation alters the trimethylation status of histone H3, impacting molecular function related to gene regulation in tumor cells. It is linked to alterations in molecular functions, specifically affecting adhesion properties and deregulating genes related to migration and invasion in tumors.

Evidence Type: Functional Mutation: K27I | Summary: The K27I mutation results in a loss of H3K27me3 immunoexpression, indicating an alteration in molecular function. The nucleotide changes 83A>T and 84G>T are part of the K27I mutation and contribute to the alteration in molecular function.

Gene→Variant (gene-first): H3-3B(3021):K27M H3-3B(3021):K27I

Genes: H3-3B(3021)

Variants: K27M K27I

[Paper-level Aggregated] PMCID: PMC4654747

Evidence Type(s): Oncogenic

Summary: Mutation: K27M | Summary: The K27M mutation in H3.3 (H3F3A) is associated with tumor development and progression in diffuse intrinsic pontine glioma (DIPG), driving distinct oncogenic programs. It is detected in biopsy samples and correlates with histological features, indicating its role in tumor development. The mutation is also associated with specific tumor subgroups (H3.1 and H3.3) and contributes to the oncogenic characteristics of the tumors. Additionally, it is used to classify and define specific tumor subtypes, particularly in H3.1 and H3.3 tumors.

Evidence Type: Oncogenic Mutation: K27I | Summary: The K27I mutation in H3.3 (H3F3A) is associated with tumor development in DIPG, contributing to the loss of trimethylation and driving oncogenic behavior. It results in a loss of H3K27me3 immunoexpression, indicating an alteration in molecular function.

Evidence Type: Oncogenic Mutation: H3-G34R/V | Summary: The H3-G34R/V mutations are restricted to cerebral hemispheres, suggesting their role in tumor development or progression.

Evidence Type: Oncogenic Mutation: H3.3-K27I | Summary: The H3.3-K27I mutation is found in pontine tumors, indicating its contribution to tumor development or progression.

Gene→Variant (gene-first): H3-3B(3021):K27M H3-3B(3021):K27I NA:H3-G34R/V NA:H3.3-K27I

Genes: H3-3B(3021) NA

Variants: K27M K27I H3-G34R/V H3.3-K27I

[Paper-level Aggregated] PMCID: PMC4654747

Evidence Type(s): Prognostic

Summary: Mutation: K27M | Summary: Patients with tumors harboring the K27M mutation in H3.3 exhibited significantly earlier relapse and more metastatic recurrences, indicating a poor prognosis. The presence of the K27M mutation correlates with disease outcome, as indicated by clinico-radiological follow-up of DIPG patients showing a significant association with metastatic relapse. Additionally, the K27M mutation is associated with a less aggressive behavior in DIPG, indicating its correlation with disease outcome independent of therapy. Furthermore, the K27M mutation in histone H3.1 is associated with a better overall survival length compared to H3.3-K27M, indicating its prognostic significance in disease outcome.

Gene→Variant (gene-first): H3-3B(3021):K27M

Genes: H3-3B(3021)

Variants: K27M

[Paper-level Aggregated] PMCID: PMC4654747

Evidence Type(s): Diagnostic

Summary: Mutation: K27M | Summary: The K27M mutation is used to classify and define specific tumor subtypes, particularly in H3.1 and H3.3 tumors, and is associated with the proneural-glioblastoma multiforme subtype, indicating its role in disease classification. It can be accurately detected by immunohistochemistry (IHC).

Gene→Variant (gene-first): H3-3B(3021):K27M

Genes: H3-3B(3021)

Variants: K27M

[Paper-level Aggregated] PMCID: PMC4654747

Evidence Type(s): Predictive

Summary: Mutation: K27M | Summary: Patients with the H3.1-K27M mutation show a better clinical response to radiotherapy, suggesting that this mutation may predict treatment response.

Gene→Variant (gene-first): H3-3B(3021):K27M

Genes: H3-3B(3021)

Variants: K27M

[Paper-level Aggregated] PMCID: PMC4477877

Evidence Type(s): Functional

Summary: Mutation: L349P | Summary: The L349P mutation alters the localization and molecular function of the ETV6 protein, preventing it from localizing to the nucleus, impacting its regulatory function, and resulting in significantly decreased transcriptional repression compared to wild-type ETV6. It is also predicted to cause significant conformational changes and affects translation and subcellular localization.

Evidence Type: Functional Mutation: N385fs | Summary: The N385fs mutation results in an abnormally truncated ETV6 protein, impairing its ability to regulate the expression of target genes and exhibiting significantly decreased transcriptional repression compared to wild-type ETV6. It is also predicted to truncate the protein at a region involved in DNA interaction, suggesting a change in its biochemical function and affecting translation and subcellular localization.

Evidence Type: Functional Mutation: P214L | Summary: The P214L mutation demonstrates significantly decreased transcriptional repression compared to wild-type ETV6 and is detectable in both cytoplasmic and nuclear fractions, indicating a potential alteration in molecular function.

Evidence Type: Functional Mutation: R369Q | Summary: The R369Q mutation shows significantly reduced transcriptional repression compared to wild-type ETV6 and is present in both cytoplasmic and nuclear fractions, suggesting an alteration in molecular function.

Evidence Type: Functional Mutation: R399C | Summary: The R399C mutation exhibits significantly decreased transcriptional repression compared to wild-type ETV6 and is detectable in both cytoplasmic and nuclear fractions, indicating a potential change in molecular function.

Gene→Variant (gene-first): ETV6(2120):L349P ETV6(2120):N385fs ETV6(2120):P214L ETV6(2120):R369Q ETV6(2120):R399C

Genes: ETV6(2120)

Variants: L349P N385fs P214L R369Q R399C

[Paper-level Aggregated] PMCID: PMC4477877

Evidence Type(s): Oncogenic

Summary: Mutation: p. N385fs | Summary: The p. N385fs mutation was found in leukemic cells and is associated with tumor development in acute lymphoblastic leukemia (ALL) and secondary myelodysplasia/acute myeloid leukemia, contributing to tumor development.

Evidence Type: Oncogenic Mutation: 415 T>C | Summary: The 415 T>C variant is a somatic mutation that contributes to tumor development, as it is present in all affected family members tested.

Evidence Type: Oncogenic Mutation: V37M | Summary: The V37M variant was identified in patients with B-ALL, indicating a potential contribution to tumor development in leukemia.

Evidence Type: Oncogenic Mutation: R181H | Summary: The R181H variant was found in patients with B-ALL, suggesting its involvement in tumor progression.

Gene→Variant (gene-first): ETV6(2120):p. N385fs IKZF1(10320):415 T>C ETV6(2120):V37M ETV6(2120):R181H

Genes: ETV6(2120) IKZF1(10320)

Variants: p. N385fs 415 T>C V37M R181H

[Paper-level Aggregated] PMCID: PMC4477877

Evidence Type(s): Predisposing

Summary: Mutation: p. L349P | Summary: The p. L349P mutation is identified as a germline variant associated with inherited susceptibility to acute leukemia, suggesting it confers inherited risk for the disease.

Evidence Type: Predisposing Mutation: p. N385fs | Summary: The N385fs mutation is identified as a germline mutation linked to inherited risk for acute leukemia, supporting its role as a predisposing factor.

Evidence Type: Predisposing Mutation: c.1153-5_1153_1delAACAG | Summary: The heterozygous deletion in ETV6 was identified in the proband and his mother, suggesting an inherited risk for acute lymphoblastic leukemia (ALL).

Evidence Type: Predisposing Mutation: V37M | Summary: The V37M variant is described as a rare germline variant, indicating it may confer inherited risk for leukemia.

Evidence Type: Predisposing Mutation: R181H | Summary: The R181H variant is classified as a rare germline variant, suggesting a potential inherited risk for leukemia.

Gene→Variant (gene-first): ETV6(2120):p. L349P ETV6(2120):p. N385fs ETV6(2120):c.1153-5_1153_1delAACAG ETV6(2120):V37M ETV6(2120):R181H

Genes: ETV6(2120)

Variants: p. L349P p. N385fs c.1153-5_1153_1delAACAG V37M R181H

[Paper-level Aggregated] PMCID: PMC4477877

Evidence Type(s): Diagnostic

Summary: Mutation: 415 T>C | Summary: The variant 415 T>C is associated with the diagnosis of thrombocytopenia and/or ALL, as it co-segregates with affected individuals in the family.

Gene→Variant (gene-first): IKZF1(10320):415 T>C

Genes: IKZF1(10320)

Variants: 415 T>C

[Paper-level Aggregated] PMCID: PMC4411002

Evidence Type(s): Oncogenic

Summary: 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. Its presence in tumor biopsies further suggests it contributes to tumor development or progression.

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): PIK3CA(5290):c.241 G>A PIK3CA(5290):p.E81K NA:c.3140 A>G [p.H1047R] NA:c.3140 A>T [p.H1047L]

Genes: PIK3CA(5290) NA

Variants: c.241 G>A p.E81K c.3140 A>G [p.H1047R] c.3140 A>T [p.H1047L]

[Paper-level Aggregated] PMCID: PMC4411002

Evidence Type(s): Predisposing

Summary: 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): PIK3CA(5290):c.241 G>A PIK3CA(5290):p.E81K

Genes: PIK3CA(5290)

Variants: c.241 G>A p.E81K

[Paper-level Aggregated] PMCID: PMC4411002

Evidence Type(s): Diagnostic

Summary: 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: Diagnostic

Gene→Variant (gene-first): PIK3CA(5290):c.241 G>A PIK3CA(5290):p.E81K

Genes: PIK3CA(5290)

Variants: c.241 G>A p.E81K

[Paper-level Aggregated] PMCID: PMC4398541

Evidence Type(s): Functional

Summary: Mutation: L23F | Summary: The L23F mutation showed increased nuclear localization of PTEN and displayed compromised/partial PIP3 catalytic activity in yeast, indicating alterations in molecular function related to subcellular localization and enzymatic activity.

Evidence Type: Functional Mutation: M35R | Summary: The M35R mutation demonstrated increased nuclear localization of PTEN and resulted in a total loss of PTEN activity in a yeast model, indicating significant alterations in its molecular function.

Evidence Type: Functional Mutation: G36R | Summary: The G36R mutation resulted in increased nuclear localization of PTEN and caused a total loss of PTEN activity in a yeast model, indicating significant alterations in its molecular function.

Evidence Type: Functional Mutation: K13E | Summary: The K13E mutation fully abrogated the nuclear accumulation of PTEN 1-375 and resulted in a total loss of phosphatase activity in vivo, indicating significant alterations in its molecular function.

Evidence Type: Functional Mutation: A34D | Summary: The A34D mutation fully abrogated the nuclear accumulation of PTEN 1-375 and caused a total loss of PTEN activity in a yeast model, indicating significant alterations in its molecular function.

Evidence Type: Functional Mutation: L42P | Summary: The L42P mutation fully abrogated the nuclear accumulation of PTEN 1-375 and caused a total loss of PTEN activity in a yeast model, indicating significant alterations in its molecular function.

Evidence Type: Functional Mutation: R15I | Summary: The R15I mutation caused a partial inhibition of nuclear accumulation of PTEN and resulted in a total loss of PTEN activity in a yeast model, indicating significant alterations in its molecular function.

Evidence Type: Functional Mutation: R15S | Summary: The R15S mutation resulted in a partial inhibition of nuclear accumulation of PTEN and caused a total loss of PTEN activity in a yeast model, indicating significant alterations in its molecular function.

Evidence Type: Functional Mutation: D24Y | Summary: The D24Y mutation caused a partial inhibition of nuclear accumulation of PTEN and resulted in a total loss of PTEN activity in a yeast model, indicating significant alterations in its molecular function.

Evidence Type: Functional Mutation: I33S | Summary: The I33S mutation resulted in a partial inhibition of nuclear accumulation of PTEN and caused a total loss of PTEN activity in a yeast model, indicating significant alterations in its molecular function.

Evidence Type: Functional Mutation: S10N | Summary: The S10N mutation did not significantly alter the nuclear/cytoplasmic distribution of PTEN and partially reduced PTEN activity in a yeast model, suggesting no functional change.

Evidence Type: Functional Mutation: Y16C | Summary: The Y16C mutation did not significantly alter the nuclear/cytoplasmic distribution of PTEN and partially reduced PTEN activity in a yeast model, indicating a moderate alteration in molecular function.

Evidence Type: Functional Mutation: A34V | Summary: The A34V mutation did not significantly alter the nuclear/cytoplasmic distribution of PTEN and partially reduced PTEN activity in a yeast model, indicating a moderate alteration in molecular function.

Evidence Type: Functional Mutation: A39V | Summary: The A39V mutation alters the nuclear accumulation of PTEN and resulted in a complete loss-of-function of PTEN's PIP3 phosphatase activity, suggesting it alters molecular function.

Evidence Type: Functional Mutation: D19A | Summary: The D19A mutation affects the cytoplasmic localization of PTEN, suggesting an alteration in its molecular function.

Evidence Type: Functional Mutation: G20A | Summary: The G20A mutation influences the cytoplasmic localization of PTEN, indicating a change in its molecular function.

Evidence Type: Functional Mutation: F21A | Summary: The F21A mutation impacts the cytoplasmic localization of PTEN, suggesting an alteration in its molecular function.

Evidence Type: Functional Mutation: K13A | Summary: The K13A mutation inhibits nuclear entry of PTEN, indicating a change in its molecular function related to localization.

Evidence Type: Functional Mutation: R14A | Summary: The R14A mutation inhibits nuclear entry of PTEN, suggesting an alteration in its molecular function.

Evidence Type: Functional Mutation: R15A | Summary: The R15A mutation inhibits nuclear entry of PTEN and resulted in a complete loss-of-function of PTEN's PIP3 phosphatase activity, indicating an alteration in molecular function.

Evidence Type: Functional Mutation: E18A | Summary: The E18A mutation inhibits nuclear accumulation of PTEN, suggesting an alteration in its molecular function.

Evidence Type: Functional Mutation: D24A | Summary: The D24A mutation inhibits nuclear entry of PTEN and led to a complete loss-of-function of PTEN's PIP3 phosphatase activity, indicating a change in biochemical function.

Evidence Type: Functional Mutation: Y16A | Summary: The Y16A mutation inhibits nuclear entry of PTEN and displayed a complete loss-of-function in PTEN's PIP3 phosphatase activity, suggesting it alters molecular function.

Evidence Type: Functional Mutation: Y27A | Summary: The Y27A mutation inhibits nuclear entry of PTEN, indicating a change in its molecular function.

Evidence Type: Functional Mutation: I28A | Summary: The I28A mutation inhibits nuclear entry of PTEN, suggesting an alteration in its molecular function.

Evidence Type: Functional Mutation: N31A | Summary: The N31A mutation inhibits nuclear entry of PTEN and did not affect PIP3 catalytic activity in yeast, suggesting a change in molecular function.

Evidence Type: Functional Mutation: I32A | Summary: The I32A mutation inhibits nuclear entry of PTEN and resulted in a complete loss-of-function of PTEN's PIP3 phosphatase activity, reflecting an alteration in molecular function.

Evidence Type: Functional Mutation: I33A | Summary: The I33A mutation inhibits nuclear entry of PTEN and partially compromised PTEN activity, indicating an alteration in molecular function.

Evidence Type: Functional Mutation: P30A | Summary: The P30A mutation inhibits nuclear entry of PTEN, suggesting an alteration in its molecular function.

Evidence Type: Functional Mutation: N12A | Summary: The N12A mutation inhibits nuclear accumulation of PTEN, indicating a change in its molecular function.

Evidence Type: Functional Mutation: M35A | Summary: The M35A mutation inhibits nuclear accumulation of PTEN and caused a complete loss-of-function of PTEN's PIP3 phosphatase activity, indicating a change in biochemical function.

Evidence Type: Functional Mutation: L42A | Summary: The L42A mutation abrogated both nuclear accumulation and PIP3 phosphatase activity of PTEN, indicating a change in molecular function.

Evidence Type: Functional Mutation: K13R | Summary: The K13R mutation alters the nuclear localization of PTEN and enhances its ability to counteract PI3K activity in a yeast model.

Evidence Type: Functional Mutation: R14K | Summary: The R14K mutation affects the nuclear localization of PTEN and maintains its phosphatase activity in vivo.

Evidence Type: Functional Mutation: R15K | Summary: The R15K mutation increases the nuclear accumulation of PTEN but does not display phosphatase activity in vivo.

Gene→Variant (gene-first): PTEN(5728):L23F PTEN(5728):M35R PTEN(5728):G36R PTEN(5728):K13E PTEN(5728):A34D PTEN(5728):L42P PTEN(5728):R15I PTEN(5728):R15S PTEN(5728):D24Y PTEN(5728):I33S PTEN(5728):S10N PTEN(5728):Y16C PTEN(5728):A34V PTEN(5728):A39V ACTG1(71):D19A PTEN(5728):G20A PTEN(5728):F21A PTEN(5728):K13A AAA1(100329167):R14A PTEN(5728):R15A PTEN(5728):E18A PTEN(5728):D24A PTEN(5728):Y16A PTEN(5728):Y27A PTEN(5728):I28A PTEN(5728):N31A PTEN(5728):I32A PTEN(5728):I33A PTEN(5728):P30A PTEN(5728):N12A PTEN(5728):M35A PTEN(5728):L42A PTEN(5728):K13R AAA1(100329167):R14K PTEN(5728):R15K

Genes: PTEN(5728) ACTG1(71) AAA1(100329167)

Variants: L23F M35R G36R K13E A34D L42P R15I R15S D24Y I33S S10N Y16C A34V A39V D19A G20A F21A K13A R14A R15A E18A D24A Y16A Y27A I28A N31A I32A I33A P30A N12A M35A L42A K13R R14K R15K

[Paragraph-level] PMCID: PMC4398541 Section: RESULTS PassageIndex: 12

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: L23F | Summary: The L23F mutation displays compromised/partial PIP3 catalytic activity in yeast, indicating an alteration in molecular function. Evidence Type: Functional | Mutation: N31A | Summary: The N31A mutation did not affect PIP3 catalytic activity in yeast but impaired the nuclear accumulation of PTEN 1-375 in mammalian cells, suggesting a change in molecular function.

Gene→Variant (gene-first): 5728:L23F 5728:N31A

Genes: 5728

Variants: L23F N31A

[Paragraph-level] PMCID: PMC4398541 Section: RESULTS PassageIndex: 10

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: K13R | Summary: The K13R mutation alters the nuclear localization of PTEN and enhances its ability to counteract PI3K activity in a yeast model. Evidence Type: Functional | Mutation: R14K | Summary: The R14K mutation affects the nuclear localization of PTEN and maintains its phosphatase activity in vivo. Evidence Type: Functional | Mutation: K13E | Summary: The K13E mutation results in a total loss of phosphatase activity in vivo. Evidence Type: Functional | Mutation: R15K | Summary: The R15K mutation increases the nuclear accumulation of PTEN but does not display phosphatase activity in vivo. Evidence Type: Functional | Mutation: K13A | Summary: The K13A mutation is part of a combined mutation that affects nuclear localization, indicating a role in PTEN's functional activity. Evidence Type: Functional | Mutation: R14A | Summary: The R14A mutation is part of a combined mutation that affects nuclear localization, indicating a role in PTEN's functional activity. Evidence Type: Functional | Mutation: R15A | Summary: The R15A mutation is part of a combined mutation that affects nuclear localization, indicating a role in PTEN's functional activity.

Gene→Variant (gene-first): 100329167:Arg14 5728:Arg15 5728:K13A 5728:K13E 5728:K13R 5728:Lys13 100329167:R14A 100329167:R14K 5728:R15A 5728:R15K

Genes: 100329167 5728

Variants: Arg14 Arg15 K13A K13E K13R Lys13 R14A R14K R15A R15K

[Paragraph-level] PMCID: PMC4398541 Section: RESULTS PassageIndex: 8

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: R15A | Summary: The R15A mutation resulted in a complete loss-of-function of PTEN's PIP3 phosphatase activity, indicating an alteration in molecular function. Evidence Type: Functional | Mutation: Y16A | Summary: The Y16A mutation displayed a complete loss-of-function in PTEN's PIP3 phosphatase activity, suggesting it alters molecular function. Evidence Type: Functional | Mutation: D24A | Summary: The D24A mutation led to a complete loss-of-function of PTEN's PIP3 phosphatase activity, indicating a change in biochemical function. Evidence Type: Functional | Mutation: I32A | Summary: The I32A mutation resulted in a complete loss-of-function of PTEN's PIP3 phosphatase activity, reflecting an alteration in molecular function. Evidence Type: Functional | Mutation: M35A | Summary: The M35A mutation caused a complete loss-of-function of PTEN's PIP3 phosphatase activity, indicating a change in biochemical function. Evidence Type: Functional | Mutation: A39V | Summary: The A39V mutation resulted in a complete loss-of-function of PTEN's PIP3 phosphatase activity, suggesting it alters molecular function. Evidence Type: Functional | Mutation: I33A | Summary: The I33A mutation partially compromised PTEN activity, indicating an alteration in molecular function. Evidence Type: Functional | Mutation: L42A | Summary: The L42A mutation abrogated both nuclear accumulation and PIP3 phosphatase activity of PTEN, indicating a change in molecular function.

Gene→Variant (gene-first): 5728:A39V 5728:D24A 5728:I32A 5728:I33A 5728:I5A 5728:K6A 5728:L42A 5728:M35A 5728:P38A 5728:Q17A 5728:R15A 5728:S10A 5728:Y16A

Genes: 5728

Variants: A39V D24A I32A I33A I5A K6A L42A M35A P38A Q17A R15A S10A Y16A

[Paragraph-level] PMCID: PMC4398541 Section: RESULTS PassageIndex: 7

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: A39V | Summary: The A39V mutation alters the nuclear accumulation of PTEN, indicating a change in its molecular function related to localization. Evidence Type: Functional | Mutation: D19A | Summary: The D19A mutation affects the cytoplasmic localization of PTEN, suggesting an alteration in its molecular function. Evidence Type: Functional | Mutation: G20A | Summary: The G20A mutation influences the cytoplasmic localization of PTEN, indicating a change in its molecular function. Evidence Type: Functional | Mutation: F21A | Summary: The F21A mutation impacts the cytoplasmic localization of PTEN, suggesting an alteration in its molecular function. Evidence Type: Functional | Mutation: K13A | Summary: The K13A mutation inhibits nuclear entry of PTEN, indicating a change in its molecular function related to localization. Evidence Type: Functional | Mutation: R14A | Summary: The R14A mutation inhibits nuclear entry of PTEN, suggesting an alteration in its molecular function. Evidence Type: Functional | Mutation: R15A | Summary: The R15A mutation inhibits nuclear entry of PTEN, indicating a change in its molecular function related to localization. Evidence Type: Functional | Mutation: E18A | Summary: The E18A mutation inhibits nuclear accumulation of PTEN, suggesting an alteration in its molecular function. Evidence Type: Functional | Mutation: D24A | Summary: The D24A mutation inhibits nuclear entry of PTEN, indicating a change in its molecular function. Evidence Type: Functional | Mutation: Y16A | Summary: The Y16A mutation inhibits nuclear entry of PTEN, suggesting an alteration in its molecular function. Evidence Type: Functional | Mutation: Y27A | Summary: The Y27A mutation inhibits nuclear entry of PTEN, indicating a change in its molecular function. Evidence Type: Functional | Mutation: I28A | Summary: The I28A mutation inhibits nuclear entry of PTEN, suggesting an alteration in its molecular function. Evidence Type: Functional | Mutation: N31A | Summary: The N31A mutation inhibits nuclear entry of PTEN, indicating a change in its molecular function. Evidence Type: Functional | Mutation: I32A | Summary: The I32A mutation inhibits nuclear entry of PTEN, suggesting an alteration in its molecular function. Evidence Type: Functional | Mutation: I33A | Summary: The I33A mutation inhibits nuclear entry of PTEN, indicating a change in its molecular function. Evidence Type: Functional | Mutation: P30A | Summary: The P30A mutation inhibits nuclear entry of PTEN, suggesting an alteration in its molecular function. Evidence Type: Functional | Mutation: N12A | Summary: The N12A mutation inhibits nuclear accumulation of PTEN, indicating a change in its molecular function. Evidence Type: Functional | Mutation: M35A | Summary: The M35A mutation inhibits nuclear accumulation of PTEN, suggesting an alteration in its molecular function.

Gene→Variant (gene-first): 5728:A39V 5728:Ala residues were mutated to Val 71:D19A 5728:D24A 5728:E18A 5728:F21A 5728:G20A 5728:I28A 5728:I32A 5728:I33A 5728:K13A 5728:L42A 5728:M35A 5728:N12A 5728:N31A 5728:P30A 100329167:R14A 5728:R15A 5728:Y16A 5728:Y27A

Genes: 5728 71 100329167

Variants: A39V Ala residues were mutated to Val D19A D24A E18A F21A G20A I28A I32A I33A K13A L42A M35A N12A N31A P30A R14A R15A Y16A Y27A

[Paragraph-level] PMCID: PMC4398541 Section: RESULTS PassageIndex: 5

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: K13E | Summary: The K13E mutation totally abrogated PTEN activity in a yeast model, indicating a significant alteration in molecular function. Evidence Type: Functional | Mutation: R15I | Summary: The R15I mutation totally abrogated PTEN activity in a yeast model, indicating a significant alteration in molecular function. Evidence Type: Functional | Mutation: R15S | Summary: The R15S mutation totally abrogated PTEN activity in a yeast model, indicating a significant alteration in molecular function. Evidence Type: Functional | Mutation: D24Y | Summary: The D24Y mutation totally abrogated PTEN activity in a yeast model, indicating a significant alteration in molecular function. Evidence Type: Functional | Mutation: I33S | Summary: The I33S mutation totally abrogated PTEN activity in a yeast model, indicating a significant alteration in molecular function. Evidence Type: Functional | Mutation: A34D | Summary: The A34D mutation totally abrogated PTEN activity in a yeast model, indicating a significant alteration in molecular function. Evidence Type: Functional | Mutation: M35R | Summary: The M35R mutation totally abrogated PTEN activity in a yeast model, indicating a significant alteration in molecular function. Evidence Type: Functional | Mutation: G36R | Summary: The G36R mutation totally abrogated PTEN activity in a yeast model, indicating a significant alteration in molecular function. Evidence Type: Functional | Mutation: L42P | Summary: The L42P mutation totally abrogated PTEN activity in a yeast model, indicating a significant alteration in molecular function. Evidence Type: Functional | Mutation: S10N | Summary: The S10N mutation partially reduced PTEN activity in a yeast model, indicating a moderate alteration in molecular function. Evidence Type: Functional | Mutation: Y16C | Summary: The Y16C mutation partially reduced PTEN activity in a yeast model, indicating a moderate alteration in molecular function. Evidence Type: Functional | Mutation: L23F | Summary: The L23F mutation partially reduced PTEN activity in a yeast model, indicating a moderate alteration in molecular function. Evidence Type: Functional | Mutation: A34V | Summary: The A34V mutation partially reduced PTEN activity in a yeast model, indicating a moderate alteration in molecular function.

Gene→Variant (gene-first): 5728:A34D 5728:A34V 5728:D24Y 5728:G36R 5728:I33S 5728:K13E 5728:L23F 5728:L42P 5728:M35R 5728:R15I 5728:R15S 5728:S10N 5728:Y16C

Genes: 5728

Variants: A34D A34V D24Y G36R I33S K13E L23F L42P M35R R15I R15S S10N Y16C

[Paragraph-level] PMCID: PMC4398541 Section: RESULTS PassageIndex: 4

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: L23F | Summary: The L23F mutation showed increased nuclear localization of PTEN, indicating an alteration in molecular function related to subcellular localization. Evidence Type: Functional | Mutation: M35R | Summary: The M35R mutation demonstrated increased nuclear localization of PTEN, suggesting a change in its molecular function. Evidence Type: Functional | Mutation: G36R | Summary: The G36R mutation resulted in increased nuclear localization of PTEN, reflecting an alteration in its molecular function. Evidence Type: Functional | Mutation: K13E | Summary: The K13E mutation fully abrogated the nuclear accumulation of PTEN 1-375, indicating a significant change in its molecular function. Evidence Type: Functional | Mutation: A34D | Summary: The A34D mutation fully abrogated the nuclear accumulation of PTEN 1-375, suggesting an alteration in its molecular function. Evidence Type: Functional | Mutation: L42P | Summary: The L42P mutation fully abrogated the nuclear accumulation of PTEN 1-375, indicating a change in its molecular function. Evidence Type: Functional | Mutation: R15I | Summary: The R15I mutation caused a partial inhibition of nuclear accumulation of PTEN, reflecting an alteration in its molecular function. Evidence Type: Functional | Mutation: R15S | Summary: The R15S mutation resulted in a partial inhibition of nuclear accumulation of PTEN, indicating a change in its molecular function. Evidence Type: Functional | Mutation: D24Y | Summary: The D24Y mutation caused a partial inhibition of nuclear accumulation of PTEN, suggesting an alteration in its molecular function. Evidence Type: Functional | Mutation: I33S | Summary: The I33S mutation resulted in a partial inhibition of nuclear accumulation of PTEN, indicating a change in its molecular function. Evidence Type: Functional | Mutation: S10N | Summary: The S10N mutation did not significantly alter the nuclear/cytoplasmic distribution of PTEN, suggesting no functional change. Evidence Type: Functional | Mutation: Y16C | Summary: The Y16C mutation did not significantly alter the nuclear/cytoplasmic distribution of PTEN, indicating no functional change. Evidence Type: Functional | Mutation: A34V | Summary: The A34V mutation did not significantly alter the nuclear/cytoplasmic distribution of PTEN, suggesting no functional change.

Gene→Variant (gene-first): 5728:A34D 5728:A34V 5728:D24Y 5728:G36R 5728:I33S 5728:K13E 5728:L23F 5728:L42P 5728:M35R 5728:R15I 5728:R15S 5728:S10N 5728:Y16C

Genes: 5728

Variants: A34D A34V D24Y G36R I33S K13E L23F L42P M35R R15I R15S S10N Y16C

[Paper-level Aggregated] PMCID: PMC4385014

Evidence Type(s): Predictive

Summary: Mutation: L858R | Summary: The L858R mutation is associated with both sensitivity and reduced sensitivity to the anti-proliferative effect of erlotinib, indicating a complex predictive relationship with therapy response.

Evidence Type: Predictive Mutation: T790M | Summary: The T790M mutation, when present alongside L858R, is evaluated for sensitivity to erlotinib and is also associated with reduced sensitivity to erlotinib treatment in the NCI-H1975 cell line, suggesting a predictive relationship with therapy response and resistance.

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

Genes: EGFR(1956)

Variants: L858R T790M

[Paper-level Aggregated] PMCID: PMC4378307

Evidence Type(s): Prognostic

Summary: Mutation: G12D | Summary: The G12D mutation in KRAS is associated with a poor prognosis in progression-free survival (PFS), serving as an independent negative prognostic factor.

Evidence Type: Prognostic Mutation: G12S | Summary: The G12S subtype of KRAS mutation is associated with poor prognosis in overall survival (OS).

Gene→Variant (gene-first): KRAS(3845):G12D KRAS(3845):G12S

Genes: KRAS(3845)

Variants: G12D G12S

[Paper-level Aggregated] PMCID: PMC4320693

Evidence Type(s): Diagnostic

Summary: Mutation: p.His1047Arg | Summary: The p.His1047Arg (H1047R) mutation is associated with a significant proportion of patients and is linked to phenotypes such as FAO, Hemihyperplasia- Multiple Lipomatosis (HHML), or macrodactyly, indicating its potential role in defining or classifying these conditions.

Evidence Type: Diagnostic Mutation: p.His1047Leu | Summary: The p.His1047Leu (H1047L) mutation is present in a notable percentage of patients and is linked to phenotypes consistent with FAO, Hemihyperplasia- Multiple Lipomatosis (HHML), or macrodactyly, suggesting its relevance in the diagnosis or classification of these conditions.

Evidence Type: Diagnostic Mutation: p.Glu545Lys | Summary: The p.Glu545Lys (E545K) mutation is found in a smaller subset of patients and is associated with the CLOVES syndrome phenotype, supporting its role in defining or classifying this condition.

Evidence Type: Diagnostic Mutation: p.Glu542Lys | Summary: The p.Glu542Lys (E542K) mutation occurs in a minority of patients and is found in individuals with phenotypes consistent with CLOVES syndrome, indicating its potential use in the diagnosis or classification of this condition.

Evidence Type: Diagnostic Mutation: p.Cys420Arg | Summary: The p.Cys420Arg (C420R) mutation, although less common, is identified in patients with CLOVES syndrome, indicating its relevance in defining or classifying this condition.

Gene→Variant (gene-first): PIK3CA(5290):p.His1047Arg PIK3CA(5290):p.His1047Leu PIK3CA(5290):p.Glu545Lys PIK3CA(5290):p.Glu542Lys PIK3CA(5290):p.Cys420Arg

Genes: PIK3CA(5290)

Variants: p.His1047Arg p.His1047Leu p.Glu545Lys p.Glu542Lys p.Cys420Arg

[Paper-level Aggregated] PMCID: PMC4239128

Evidence Type(s): Oncogenic

Summary: Mutation: 1799T > A; p.V600E | Summary: The BRAF p.V600E mutation is implicated in tumor development and progression, contributing to the malignancy's characteristics.

Evidence Type: Oncogenic Mutation: V600E | Summary: The BRAF V600E mutation contributes to the development and progression of the poorly differentiated intrahepatic cholangiocarcinoma in this patient.

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

Genes: BRAF(673)

Variants: 1799T > A p.V600E V600E

[Paper-level Aggregated] PMCID: PMC4239128

Evidence Type(s): Predictive

Summary: Mutation: 1799T > A; p.V600E | Summary: The BRAF p.V600E mutation is associated with a potential vulnerability to BRAF inhibition and is correlated with the patient's response to dual therapy using dabrafenib and trametinib, indicating its predictive value for treatment efficacy.

Evidence Type: Predictive Mutation: V600E | Summary: The BRAF V600E mutation is associated with the patient's response to dual therapy with dabrafenib and trametinib, indicating its predictive value for treatment efficacy.

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

Genes: BRAF(673)

Variants: 1799T > A p.V600E V600E

[Paper-level Aggregated] PMCID: PMC4234187

Evidence Type(s): Functional

Summary: Mutation: C118S | Summary: The C118S mutation alters the molecular function of Ras by blocking activation, affecting the ability of eNOS to stimulate the MAPK pathway, and influencing signaling pathways related to oncogenic activity. It also alters tumor size and incidence of adenomas, as evidenced by reduced P-Akt levels and changes in P-Erk1/2 levels upon EGF treatment. Additionally, the presence of the KrasC118S allele suggests a change in molecular or biochemical function, although specific functional impacts are not detailed.

Evidence Type: Functional Mutation: S1177D | Summary: The S1177D mutation in eNOS alters the levels of phosphorylated Erk1/2, demonstrating a change in biochemical function.

Evidence Type: Functional Mutation: G13D | Summary: The G13D mutation, when combined with C118S, affects the molecular function of Kras, influencing signaling pathways related to oncogenic activity.

Gene→Variant (gene-first): NOS2(4843):C118S NOS3(4846):S1177D KRAS(3845):G13D

Genes: NOS2(4843) NOS3(4846) KRAS(3845)

Variants: C118S S1177D G13D

[Paper-level Aggregated] PMCID: PMC4234187

Evidence Type(s): Oncogenic

Summary: Mutation: C118S | Summary: The C118S mutation in the Kras gene is implicated in tumorigenesis, contributing to tumor development and progression. It is associated with a reduction in tumor burden and a shift towards smaller tumors in mice, and it is involved in the sensitivity of tumor initiation to Ras protein levels. The KrasC118S allele is also described as having a negative effect on lung tumorigenesis, suggesting it may suppress the tumorigenic activity of the oncogenic Kras allele. Additionally, it is investigated for its role in tumorigenesis, showing that it impedes urethane-induced lung tumor development.

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

Evidence Type: Oncogenic Mutation: Q61R | Summary: The Q61R mutation in the native Kras allele is identified as oncogenic, contributing to tumor development in the analyzed lung tumors from Kras+/C118S mice.

Evidence Type: Oncogenic Mutation: Q61R/L | Summary: The Q61R/L mutations in Kras are characterized as oncogenic, contributing to tumor development and progression in the context of urethane-induced lung tumors.

Evidence Type: Oncogenic Mutation: G13D | Summary: The KrasG13D mutation is described as an oncogenic mutant, indicating its role in tumor progression.

Gene→Variant (gene-first): NOS2(4843):C118S KRAS(3845):G12D NRAS(4893):Q61R KRAS(3845):Q61R/L KRAS(3845):G13D

Genes: NOS2(4843) KRAS(3845) NRAS(4893)

Variants: C118S G12D Q61R Q61R/L G13D

[Paper-level Aggregated] PMCID: PMC4159563

Evidence Type(s): Functional

Summary: Mutation: p.Glu545Gly | Summary: The p.Glu545Gly alteration in PIK3CA is a mutation that may alter the molecular function of the protein, contributing to tumorigenesis.

Evidence Type: Functional Mutation: p.Gly328Val | Summary: The p.Gly328Val substitution in ACVR1 is a mutation that may affect the molecular function of the protein, potentially playing a role in tumor development.

Gene→Variant (gene-first): PIK3CA(5290):p.Glu545Gly ACVR1(90):p.Gly328Val

Genes: PIK3CA(5290) ACVR1(90)

Variants: p.Glu545Gly p.Gly328Val

[Paper-level Aggregated] PMCID: PMC4159563

Evidence Type(s): Oncogenic

Summary: Mutation: K27M | Summary: The K27M mutation in histone H3 is associated with high-grade astrocytomas and contributes to tumor development and progression in diffuse intrinsic pontine glioma (DIPG). It is linked to leptomeningeal dissemination and is considered an oncogenic variant due to its role in tumor development.

Gene→Variant (gene-first): ACVR1(90):K27M

Genes: ACVR1(90)

Variants: K27M

[Paper-level Aggregated] PMCID: PMC4159563

Evidence Type(s): Prognostic

Summary: Mutation: K27M | Summary: The K27M-H3 mutation correlates with disease behavior and outcomes in pediatric brainstem gliomas, indicating it may not predict outcomes accurately according to the current WHO grading scheme. It is associated with worse overall survival in patients with leptomeningeal spread, averaging 0.63 years compared to 1.84 years for wild-type cases. Additionally, the K27M mutation in histone H3 is linked to worse overall survival in DIPG patients compared to those without histone mutations, highlighting its prognostic significance.

Gene→Variant (gene-first): ACVR1(90):K27M

Genes: ACVR1(90)

Variants: K27M

[Paper-level Aggregated] PMCID: PMC4159563

Evidence Type(s): Diagnostic

Summary: Mutation: K27M | Summary: The presence of the K27M-H3 mutation is used to classify and define the histological subtype of astrocytomas in DIPG cases. It is associated with specific histological features that can help in tumor classification, serving as a diagnostic marker for tumors in DIPG patients.

Gene→Variant (gene-first): ACVR1(90):K27M

Genes: ACVR1(90)

Variants: K27M

[Paper-level Aggregated] PMCID: PMC4150988

Evidence Type(s): Functional

Summary: Mutation: p.M90I | Summary: The p.M90I mutation is being studied for its role in altering the molecular function of RIT1 in the context of human cancer pathogenesis and is associated with human primary lung adenocarcinomas, suggesting it may contribute to tumor development or progression.

Gene→Variant (gene-first): RIT1(6016):p.M90I

Genes: RIT1(6016)

Variants: p.M90I

[Paper-level Aggregated] PMCID: PMC4150988

Evidence Type(s): Oncogenic

Summary: Mutation: p.M90I | Summary: The p.M90I mutation in RIT1 is associated with tumor development or progression, being recurrently observed in lung adenocarcinoma and myeloid malignancies. It is suggested to contribute to tumor development based on its presence in 'oncogene-negative' lung cancer cell lines.

Evidence Type: Oncogenic Mutation: p.A77P | Summary: The p.A77P mutation in RIT1 is associated with tumor development as it was observed in a recurrent alteration among mutated samples.

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

Evidence Type: Oncogenic Mutation: F82L | Summary: The F82L mutation is associated with tumor development or progression, as it has been observed in lung adenocarcinoma and myeloid malignancies.

Evidence Type: Oncogenic Mutation: G12V | Summary: The KRAS G12V mutation is associated with inducing cellular transformation and tumor formation in NIH3T3 cells.

Evidence Type: Oncogenic Mutation: L858R | Summary: The EGFR L858R mutation contributes to tumor formation, as evidenced by its ability to induce significant colony formation in soft agar.

Evidence Type: Oncogenic Mutation: Q79L | Summary: The RIT1 Q79L mutation is capable of inducing cellular transformation and tumor formation in NIH3T3 cells.

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

Gene→Variant (gene-first): RIT1(6016):p.M90I RIT1(6016):p.A77P RIT1(6016):p.R122L RIT1(6016):F82L KRAS(3845):G12V EGFR(1956):L858R RIT1(6016):Q79L RIT1(6016):Q40L

Genes: RIT1(6016) KRAS(3845) EGFR(1956)

Variants: p.M90I p.A77P p.R122L F82L G12V L858R Q79L Q40L

[Paper-level Aggregated] PMCID: PMC4150988

Evidence Type(s): Predisposing

Summary: Mutation: p.A77S | Summary: The p.A77S mutation may represent a rare germline variant, suggesting a potential inherited risk for disease, although this is unlikely based on the absence in normal genome data.

Evidence Type: Predisposing

Gene→Variant (gene-first): RIT1(6016):p.A77S

Genes: RIT1(6016)

Variants: p.A77S

[Paper-level Aggregated] PMCID: PMC3997489

Evidence Type(s): Oncogenic

Summary: Mutation: K27M | Summary: The K27M mutation is associated with the development and progression of Diffuse Intrinsic Pontine Glioma (DIPG), contributing to the tumor's oncogenic characteristics.

Gene→Variant (gene-first): H3-3B(3021):K27M

Genes: H3-3B(3021)

Variants: K27M

[Paper-level Aggregated] PMCID: PMC3997489

Evidence Type(s): Diagnostic

Summary: Mutation: K27M | Summary: The presence of the K27M mutation is used to classify and define the molecular subgroup of Diffuse Intrinsic Pontine Glioma (DIPG), aiding in the understanding of its genetic drivers.

Gene→Variant (gene-first): H3-3B(3021):K27M

Genes: H3-3B(3021)

Variants: K27M

[Paper-level Aggregated] PMCID: PMC3973211

Evidence Type(s): Functional

Summary: Mutation: R273H | Summary: The R273H mutation is involved in specific gene enrichment profiles and was tested for its effects on CYP3A4 expression, suggesting alterations in molecular or biochemical function related to serine-hydrolase pathways.

Evidence Type: Functional Mutation: R248 | Summary: The p53 R248 mutation induces higher expression of the CYP3A4 protein, indicating an alteration in molecular function.

Evidence Type: Functional Mutation: R282 | Summary: The p53 R282 mutation also induces higher expression of the CYP3A4 protein, demonstrating a change in molecular function.

Evidence Type: Functional Mutation: R175H | Summary: The p53 R175H mutation was tested for its effects on CYP3A4 expression, indicating a potential alteration in molecular function.

Evidence Type: Functional Mutation: R282W | Summary: The R282W mutation significantly upregulates CYP3A4 mRNA and protein levels, indicating an alteration in molecular function related to drug metabolism.

Gene→Variant (gene-first): TP53(7157):R273H TP53(7157):R248 TP53(7157):R282 TP53(7157):R175H TP53(7157):R282W

Genes: TP53(7157)

Variants: R273H R248 R282 R175H R282W

[Paper-level Aggregated] PMCID: PMC3973211

Evidence Type(s): Oncogenic

Summary: Mutation: R248 | Summary: The R248 mutation contributes to tumor development or progression, as evidenced by survival analysis in mice and increased expression of CYP3A4, suggesting its role in tumor behavior and association with mortality mutations.

Evidence Type: Oncogenic Mutation: R282 | Summary: The R282 mutation contributes to tumor development or progression, indicated by survival analysis in cancer patients and increased expression of CYP3A4, highlighting its oncogenic potential and association with chemoresistance.

Evidence Type: Oncogenic Mutation: R248W | Summary: The R248W mutation is implicated in tumor development and progression through its association with p53 mortality mutations and chemoresistance, as well as contributing to increased expression of CYP3A4.

Evidence Type: Oncogenic Mutation: R282W | Summary: The R282W mutation contributes to tumor development by displaying higher expression and resistance to chemotherapeutic drugs, indicating its oncogenic potential and association with mortality mutations.

Evidence Type: Oncogenic Mutation: R175H | Summary: The R175H mutation is part of p53 gain-of-function mutations that contribute to tumor development and progression, as indicated by its association with chemoresistance.

Evidence Type: Oncogenic Mutation: R273 | Summary: The R273 mutation is linked to lower levels of CYP3A4 expression compared to mortality-associated mutations, suggesting its involvement in tumor behavior.

Evidence Type: Oncogenic Mutation: R273H | Summary: The R273H mutation is associated with p53 mortality mutations that contribute to tumor development and progression.

Gene→Variant (gene-first): TP53(7157):R248 TP53(7157):R282 TP53(7157):R248W TP53(7157):R282W TP53(7157):R175H TP53(7157):R273 TP53(7157):R273H

Genes: TP53(7157)

Variants: R248 R282 R248W R282W R175H R273 R273H

[Paper-level Aggregated] PMCID: PMC3973211

Evidence Type(s): Prognostic

Summary: Mutation: Arg248 | Summary: The Arg248 mutation is associated with shorter patient survival, indicating a correlation with disease outcome independent of therapy. Patients carrying p53 mutations at Arg248 had significantly shorter overall survival time compared to those with nonsense mutations, further supporting its prognostic significance in human cancers.

Evidence Type: Prognostic Mutation: Arg282 | Summary: The Arg282 mutation is linked to shorter patient survival, highlighting its prognostic relevance in cancer outcomes. Similar to Arg248, mutations at Arg282 were associated with a higher hazard ratio in survival analysis, suggesting a negative impact on overall survival.

Evidence Type: Prognostic Mutation: R248 | Summary: The R248 mutation is associated with shorter patient survival, indicating a correlation with disease outcome independent of therapy.

Evidence Type: Prognostic Mutation: R282 | Summary: The R282 mutation is associated with shorter patient survival, indicating a correlation with disease outcome independent of therapy.

Evidence Type: Prognostic Mutation: R248Q/W | Summary: The R248Q/W mutations are associated with increased mortality in colorectal cancer, indicating a correlation with disease outcome independent of therapy.

Evidence Type: Prognostic Mutation: R249S | Summary: Very few cases of the R249S mutation were available for analysis, limiting the ability to draw conclusions about its impact on survival.

Evidence Type: Prognostic

Gene→Variant (gene-first): TP53(7157):Arg248 TP53(7157):Arg282 TP53(7157):R248 TP53(7157):R282 TP53(7157):R248Q/W TP53(7157):R249S

Genes: TP53(7157)

Variants: Arg248 Arg282 R248 R282 R248Q/W R249S

[Paper-level Aggregated] PMCID: PMC3973211

Evidence Type(s): Predictive

Summary: Mutation: R248W | Summary: The R248W mutation is associated with increased viability in response to etoposide treatment, suggesting a correlation with resistance to chemotherapy.

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

Evidence Type: Predictive Mutation: R282W | Summary: The R282W mutation is linked to higher viability after etoposide treatment, indicating a potential role in chemotherapy resistance.

Gene→Variant (gene-first): TP53(7157):R248W TP53(7157):R282 TP53(7157):R282W

Genes: TP53(7157)

Variants: R248W R282 R282W

[Paper-level Aggregated] PMCID: PMC3923676

Evidence Type(s): Functional

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

Evidence Type: Functional Mutation: E384X | Summary: The E384X mutation results in nearly complete loss of function of the ERRFI1 protein, as indicated by the allele-specific expression data from the RNASeq analysis. This alteration in molecular function is significant in the context of the patient's tumor.

Gene→Variant (gene-first): DNAH5(1767):G C BRCA1(672):E384X

Genes: DNAH5(1767) BRCA1(672)

Variants: G C E384X

[Paper-level Aggregated] PMCID: PMC3923676

Evidence Type(s): Oncogenic

Summary: Mutation: E384X | Summary: The E384X mutation in ERRFI1 is described as a somatic loss of function mutation that inactivates the gene, contributing to tumor development and progression, particularly in advanced cholangiocarcinoma and in the context of the patient's metastatic, recurrent/refractory SIC. The mutation acts as a negative regulator of EGFR and suggests nearly complete loss of function of ERRFI1 in the tumor, indicating its role in cancer progression.

Gene→Variant (gene-first): BRCA1(672):E384X

Genes: BRCA1(672)

Variants: E384X

[Paper-level Aggregated] PMCID: PMC3923676

Evidence Type(s): Predictive

Summary: Mutation: E384X | Summary: The E384X mutation is associated with a robust disease regression in a patient treated with erlotinib, indicating its potential role in predicting response to EGFR kinase inhibitors.

Gene→Variant (gene-first): BRCA1(672):E384X

Genes: BRCA1(672)

Variants: E384X

[Paper-level Aggregated] PMCID: PMC3727232

Evidence Type(s): Functional

Summary: Mutation: p.V676fs | Summary: The CIC mutation p.V676fs alters molecular or biochemical function, contributing to the tumor's genetic profile.

Evidence Type: Functional Mutation: p.S726R | Summary: The CIC mutation p.S726R alters molecular or biochemical function, contributing to the tumor's genetic profile.

Evidence Type: Functional Mutation: p.D1722V | Summary: The CHD2 mutation p.D1722V alters molecular or biochemical function, contributing to the tumor's genetic profile.

Evidence Type: Functional Mutation: p.P101L | Summary: The STYK1 mutation p.P101L alters molecular or biochemical function, contributing to the tumor's genetic profile.

Gene→Variant (gene-first): CIC(23152):p.V676fs CIC(23152):p.S726R CHD2(1106):p.D1722V CDKN2A(1029):p.P101L

Genes: CIC(23152) CHD2(1106) CDKN2A(1029)

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

[Paper-level Aggregated] PMCID: PMC3727232

Evidence Type(s): Oncogenic

Summary: Mutation: p.K27M | Summary: The H3F3A:p.K27M mutation is associated with tumor development in supratentorial diffuse astrocytomas and certain gliomas, indicating its role as a somatic variant contributing to oncogenesis.

Evidence Type: Oncogenic Mutation: p.V600E | Summary: The BRAF:p.V600E mutation is frequently observed in pleomorphic xanthoastrocytomas and other gliomas, suggesting its contribution to tumor development and progression as a somatic variant.

Evidence Type: Oncogenic Mutation: p.R132H | Summary: The IDH1 mutation p.R132H is associated with tumor development or progression in the context of oligodendroglioma.

Gene→Variant (gene-first): H3-3B(3021):p.K27M BRAF(673):p.V600E IDH1(3417):p.R132H

Genes: H3-3B(3021) BRAF(673) IDH1(3417)

Variants: p.K27M p.V600E p.R132H

[Paper-level Aggregated] PMCID: PMC3542862

Evidence Type(s): Functional

Summary: 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: Functional Mutation: H1047R | Summary: The H1047R mutation in PIK3CA is associated with increased intracellular AKT phosphorylation, contributing to tumor development and progression.

Gene→Variant (gene-first): PIK3CA(5290):p.Glu542 PIK3CA(5290):H1047R

Genes: PIK3CA(5290)

Variants: p.Glu542 H1047R

[Paper-level Aggregated] PMCID: PMC3542862

Evidence Type(s): Oncogenic

Summary: Mutation: E542K | Summary: The E542K mutation in PIK3CA is identified as a gain-of-function somatic mutation in the helical domain, contributing to tumor development in patients with macrodactyly.

Evidence Type: Oncogenic Mutation: H1047L | Summary: The H1047L mutation in PIK3CA is a somatic gain-of-function mutation located in the kinase domain, associated with tumor progression in macrodactyly patients.

Evidence Type: Oncogenic Mutation: H1047R | Summary: The H1047R mutation in PIK3CA is a somatic mutation in the kinase domain, linked to increased intracellular AKT phosphorylation and contributing to tumor development and progression in macrodactyly patients.

Evidence Type: Oncogenic Mutation: R115P | Summary: The R115P mutation in PIK3CA is a somatic mutation present in lesional tissue but absent in blood, suggesting its role in tumor development in macrodactyly patients. It is located in a linker sequence and confirmed through exome sequencing.

Evidence Type: Oncogenic Mutation: R115L | Summary: The R115L mutation is associated with squamous cell carcinoma, indicating that mutations at p.Arg115 contribute to tumor development or progression.

Evidence Type: Oncogenic Mutation: p.Arg115 | Summary: Mutations at p.Arg115 in PIK3CA are annotated in the context of cancer, indicating their potential role in oncogenesis.

Gene→Variant (gene-first): PIK3CA(5290):E542K PIK3CA(5290):H1047L PIK3CA(5290):H1047R PDK1(5163):R115P PIK3CA(5290):R115L PIK3CA(5290):p.Arg115

Genes: PIK3CA(5290) PDK1(5163)

Variants: E542K H1047L H1047R R115P R115L p.Arg115

[Paper-level Aggregated] PMCID: PMC3542862

Evidence Type(s): Diagnostic

Summary: 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: Diagnostic

Gene→Variant (gene-first): PDK1(5163):R115P

Genes: PDK1(5163)

Variants: R115P

[Paper-level Aggregated] PMCID: PMC3483540

Evidence Type(s): Oncogenic

Summary: Mutation: L858R | Summary: The L858R mutation in EGFR is identified as a driver mutation contributing to lung adenocarcinoma.

Evidence Type: Oncogenic Mutation: G719A | Summary: The G719A mutation in EGFR is recognized as a driver mutation associated with lung adenocarcinoma.

Evidence Type: Oncogenic Mutation: G12C | Summary: The G12C mutation in KRAS is classified as a driver mutation that contributes to lung cancer.

Evidence Type: Oncogenic Mutation: G12V | Summary: The G12V mutation in KRAS is identified as a driver mutation involved in lung cancer development.

Evidence Type: Oncogenic Mutation: G12D | Summary: The G12D mutation in KRAS is recognized as a driver mutation contributing to lung cancer.

Evidence Type: Oncogenic Mutation: G12S | Summary: The G12S mutation in KRAS is classified as a driver mutation associated with lung cancer.

Evidence Type: Oncogenic Mutation: G13C | Summary: The G13C mutation in KRAS is identified as a driver mutation contributing to lung cancer.

Evidence Type: Oncogenic Mutation: G13D | Summary: The G13D mutation in KRAS is recognized as a driver mutation involved in lung cancer.

Evidence Type: Oncogenic Mutation: Q61H | Summary: The Q61H mutation in NRAS is classified as a driver mutation associated with lung cancer.

Evidence Type: Oncogenic Mutation: Q61L | Summary: The Q61L mutation in NRAS is identified as a driver mutation contributing to lung cancer.

Evidence Type: Oncogenic Mutation: Q61K | Summary: The Q61K mutation in NRAS is recognized as a driver mutation involved in lung cancer.

Evidence Type: Oncogenic Mutation: H1047R | Summary: The H1047R mutation in PIK3CA is classified as a driver mutation associated with lung cancer.

Evidence Type: Oncogenic Mutation: E555K | Summary: The E555K mutation in PIK3CA is identified as a driver mutation contributing to lung cancer.

Evidence Type: Oncogenic Mutation: V600E | Summary: The V600E mutation in BRAF is recognized as a driver mutation involved in lung cancer.

Evidence Type: Oncogenic Mutation: D32G | Summary: The D32G mutation in CTNNB1 is classified as a driver mutation associated with lung adenocarcinoma.

Evidence Type: Oncogenic Mutation: M1124D | Summary: The M1124D mutation in MET is identified as a driver mutation contributing to lung adenocarcinoma.

Evidence Type: Oncogenic Mutation: C > A | Summary: The C > A transversion is identified as a more frequent somatic mutation in lung cancers of smokers, suggesting its contribution to tumor development or progression.

Evidence Type: Oncogenic Mutation: T > G | Summary: The T > G transversion is noted as a more common somatic mutation in lung cancers of never-smokers, indicating its potential role in tumor development or progression.

Gene→Variant (gene-first): EGFR(1956):L858R EGFR(1956):G719A KRAS(3845):G12C KRAS(3845):G12V KRAS(3845):G12D KRAS(3845):G12S KRAS(3845):G13C KRAS(3845):G13D KRAS(3845):Q61H NRAS(4893):Q61L NRAS(4893):Q61K PIK3CA(5290):H1047R LMTK2(22853):E555K BRAF(673):V600E CTNNB1(1499):D32G CTNNB1(1499):M1124D FBLN2(2199):C > A FBLN2(2199):T > G

Genes: EGFR(1956) KRAS(3845) NRAS(4893) PIK3CA(5290) LMTK2(22853) BRAF(673) CTNNB1(1499) FBLN2(2199)

Variants: L858R G719A G12C G12V G12D G12S G13C G13D Q61H Q61L Q61K H1047R E555K V600E D32G M1124D C > A T > G

[Paper-level Aggregated] PMCID: PMC3461408

Evidence Type(s): Oncogenic

Summary: Mutation: p.His1047Leu | Summary: The p.His1047Leu mutation in PIK3CA is identified as a cancer-associated mutation contributing to tumor development in a patient with a syndrome of congenital overgrowth.

Evidence Type: Oncogenic Mutation: p.His1047Arg | Summary: The p.His1047Arg mutation in PIK3CA is identified as a cancer-associated mutation found in multiple patients with overlapping syndromes, indicating its role in tumor progression.

Gene→Variant (gene-first): PIK3CA(5290):p.His1047Leu PIK3CA(5290):p.His1047Arg

Genes: PIK3CA(5290)

Variants: p.His1047Leu p.His1047Arg

[Paper-level Aggregated] PMCID: PMC3422615

Evidence Type(s): Functional

Summary: Mutation: K27M | Summary: The K27M mutation alters molecular characteristics in H3.3, impacting the biochemical function relevant to tumor biology.

Gene→Variant (gene-first): H3-3B(3021):K27M

Genes: H3-3B(3021)

Variants: K27M

[Paper-level Aggregated] PMCID: PMC3422615

Evidence Type(s): Oncogenic

Summary: Mutation: K27M | Summary: The K27M-H3.3 mutation is prevalent in pediatric glioblastomas and is recurrently identified in DIPG samples, contributing to tumor development and progression. It is associated with specific chromosomal alterations and significant focal copy number alterations, indicating its role in tumor biology. The mutation is found in DIPG samples that also harbor ATRX mutations, suggesting its involvement in tumor progression. Additionally, the K27M mutation correlates with poor survival outcomes in affected patients, highlighting its oncogenic significance.

Evidence Type: Oncogenic Mutation: G34V/R | Summary: The G34V/R mutation is associated with GBM samples that also carry ATRX and TP53 mutations, indicating its contribution to tumor development.

Gene→Variant (gene-first): H3-3B(3021):K27M H3-3B(3021):G34V/R

Genes: H3-3B(3021)

Variants: K27M G34V/R

[Paper-level Aggregated] PMCID: PMC3422615

Evidence Type(s): Prognostic

Summary: Mutation: K27M | Summary: The K27M-H3.3 mutation is universally associated with short survival in DIPG and correlates with significantly worse overall survival in DIPG patients compared to wild-type tumors, indicating its prognostic significance in disease outcome.

Gene→Variant (gene-first): H3-3B(3021):K27M

Genes: H3-3B(3021)

Variants: K27M

[Paper-level Aggregated] PMCID: PMC3422615

Evidence Type(s): Diagnostic

Summary: Mutation: K27M | Summary: The K27M-H3.3 mutation is used to define clinically and biologically distinct subgroups in pediatric glioblastomas, supporting its role in diagnostic testing.

Gene→Variant (gene-first): H3-3B(3021):K27M

Genes: H3-3B(3021)

Variants: K27M

[Paper-level Aggregated] PMCID: PMC3383766

Evidence Type(s): Functional

Summary: Mutation: S184L | Summary: The S184L mutation in MAP2K4 alters molecular function, likely affecting splicing and kinase pathway activation.

Evidence Type: Functional Mutation: M294K | Summary: The M294K mutation in GATA3 is associated with functional inactivation, as indicated by the presence of truncation events and other mutations in the gene.

Evidence Type: Functional Mutation: C77F | Summary: The C77F mutation in AKT1 alters molecular function.

Evidence Type: Functional Mutation: S11F | Summary: The S11F mutation in AKT2 affects molecular function.

Evidence Type: Functional Mutation: S375F | Summary: The S375F mutation in RPS6KB1 alters biochemical function.

Gene→Variant (gene-first): ARID4B(51742):S184L GATA3(2625):M294K AKT1(207):C77F AKT2(208):S11F FOXA1(3169):S375F

Genes: ARID4B(51742) GATA3(2625) AKT1(207) AKT2(208) FOXA1(3169)

Variants: S184L M294K C77F S11F S375F

[Paper-level Aggregated] PMCID: PMC3383766

Evidence Type(s): Oncogenic

Summary: Mutation: G168E | Summary: The G168E mutation in RUNX1 is implicated in tumor development and progression, particularly in the M2 subtype of AML.

Evidence Type: Oncogenic Mutation: R166Q | Summary: The R166Q mutation in RUNX1 contributes to tumor development and is associated with the M2 subtype of AML.

Evidence Type: Oncogenic Mutation: R169K | Summary: The R169K mutation in RUNX1 is involved in tumor progression and is relevant to the M2 subtype of AML.

Evidence Type: Oncogenic Mutation: K700E | Summary: The K700E mutation in SF3B1 is implicated in tumor development and is associated with myelodysplastic syndromes (MDS) and chronic lymphocytic leukemia (CLL).

Evidence Type: Oncogenic Mutation: K666Q | Summary: The K666Q mutation in SF3B1 contributes to tumor development and is relevant in the context of MDS and CLL.

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

Evidence Type: Oncogenic Mutation: V184I | Summary: The V184I mutation in AGTR2 is linked to angiotensin signaling, indicating its potential contribution to tumor development or progression.

Evidence Type: Oncogenic Mutation: M294K | Summary: The recurrent M294K mutation in GATA3 suggests a role in tumor development, reinforcing the conclusion that GATA3 acts as a tumor suppressor.

Evidence Type: Oncogenic Mutation: V777L | Summary: The V777L mutation in ERBB2 is associated with tumor development, particularly in the context of gefitinib-activating mutations in lung cancer.

Evidence Type: Oncogenic Mutation: A829V | Summary: The A829V mutation in DDR1 is implicated in tumor development and progression.

Evidence Type: Oncogenic Mutation: R611C | Summary: The R611C mutation in DDR1 contributes to tumor development.

Evidence Type: Oncogenic Mutation: E583D | Summary: The E583D mutation in DDR2 is associated with oncogenic activity.

Evidence Type: Oncogenic Mutation: D735H | Summary: The D735H mutation in CSF1R is linked to tumor progression.

Evidence Type: Oncogenic Mutation: M875L | Summary: The M875L mutation in CSF1R contributes to tumor development.

Evidence Type: Oncogenic Mutation: E924K | Summary: The E924K mutation in PDGFRA is associated with oncogenic behavior.

Gene→Variant (gene-first): KMT2B(9757):G168E RUNX1(861):R166Q CYP19A1(1588):R169K SF3B1(23451):K700E SF3B1(23451):K666Q AGTR2(186):R251H AGTR2(186):V184I GATA3(2625):M294K ERBB2(2064):V777L DDR1(780):A829V DDR1(780):R611C NRG1(3084):E583D ARNT(405):D735H PDGFRA(5156):M875L EPHB2(2048):E924K

Genes: KMT2B(9757) RUNX1(861) CYP19A1(1588) SF3B1(23451) AGTR2(186) GATA3(2625) ERBB2(2064) DDR1(780) NRG1(3084) ARNT(405) PDGFRA(5156) EPHB2(2048)

Variants: G168E R166Q R169K K700E K666Q R251H V184I M294K V777L A829V R611C E583D D735H M875L E924K

[Paper-level Aggregated] PMCID: PMC3378484

Evidence Type(s): Functional

Summary: Mutation: N564D | Summary: The N564D mutation is associated with altered lipid binding activities, displaying high levels of hydrophobic interaction with neutral lipids in the basal state, and modifying polar contacts in the C2 domain, which may influence interactions with phospholipid headgroups.

Evidence Type: Functional Mutation: K942 | Summary: The mutation K942 is 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 important in the recognition of the substrate PtdIns(4,5)P2 head group, suggesting it alters molecular or biochemical function. The R949D variant shows much reduced binding to anionic lipids, indicating an alteration in molecular function related to lipid interactions.

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.

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: 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: C420R | Summary: The C420R mutation alters molecular function by displaying high levels of hydrophobic interaction with neutral lipids in the basal state and modifies molecular interactions within the C2 domain, potentially affecting lipid binding due to changes in hydrophobicity.

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 and disrupts contacts in the C2/helical-nSH2 region, potentially exposing hydrophobic areas that could affect lipid binding.

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 and shows increased lipid binding levels compared to other p110 isoforms.

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, induces a global conformational change that may impact the molecular activity of the kinase C-lobe, and suggests a functional alteration in its biochemical properties.

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.

Gene→Variant (gene-first): PIK3R1(5295):N564D PIK3CG(5294):K942 PIK3CG(5294):R949 PIK3CA(5290):deletion of residues 1051-1068 PIK3CA(5290):D915N PIK3CG(5294):K942Q PIK3CA(5290):C420R PIK3CA(5290):E545K PIK3CA(5290):G1049R PIK3CA(5290):H1047L PIK3CA(5290):H1047R PIK3CA(5290):H1047

Genes: PIK3R1(5295) PIK3CG(5294) PIK3CA(5290)

Variants: N564D K942 R949 deletion of residues 1051-1068 D915N K942Q C420R E545K G1049R H1047L H1047R H1047

[Paper-level Aggregated] PMCID: PMC3378484

Evidence Type(s): Oncogenic

Summary: Mutation: E545K | Summary: The E545K mutation shows the highest basal activity and lipid binding, mimicking the activated wild-type p110alpha, indicating its role in tumor development. It is described as activating, suggesting it plays a role in tumor development or progression.

Evidence Type: Oncogenic Mutation: H1047R | Summary: The H1047R mutant exhibits increased basal kinase activities and lipid binding, contributing to tumor progression. It is described as an oncogenic mutant, indicating its contribution to tumor development or progression. The mutation is characterized as activating, suggesting it plays a role in tumor development or progression.

Evidence Type: Oncogenic Mutation: C420R | Summary: The C420R mutation shows increased basal kinase activity and lipid binding, suggesting its involvement in oncogenesis. It is characterized as activating, indicating its contribution to tumor development or progression.

Evidence Type: Oncogenic Mutation: M1043I | Summary: The M1043I mutation is associated with increased basal kinase activity and lipid binding, indicating its oncogenic potential. It is noted to be activating, which implies its involvement in tumor development or progression.

Evidence Type: Oncogenic Mutation: H1047L | Summary: The H1047L mutation demonstrates increased basal kinase activity and lipid binding, contributing to tumor development. It is characterized as activating, indicating its contribution to tumor development or progression.

Evidence Type: Oncogenic Mutation: G1049R | Summary: The G1049R mutation shows increased basal kinase activity and lipid binding, suggesting its role in oncogenesis. It is noted to be activating, which implies its involvement in tumor development or progression.

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): PIK3CA(5290):E545K PIK3CA(5290):H1047R PIK3CA(5290):C420R PIK3CA(5290):M1043I PIK3CA(5290):H1047L PIK3CA(5290):G1049R PIK3CA(5290):D915N

Genes: PIK3CA(5290)

Variants: E545K H1047R C420R M1043I H1047L G1049R D915N

[Paper-level Aggregated] PMCID: PMC3366948

Evidence Type(s): Functional

Summary: Mutation: A35V | Summary: The A35V variant was present in the CCRF-CEM cell line and one additional clone, but analysis could not identify major differences in transforming properties compared to wild type TYK2.

Evidence Type: Functional Mutation: C192Y | Summary: The C192Y mutation was only found in the JURKAT line and was absent in other clones, with no significant differences in autophosphorylation observed compared to wild type TYK2.

Gene→Variant (gene-first): MST1R(4486):A35V PMS2(5395):C192Y

Genes: MST1R(4486) PMS2(5395)

Variants: A35V C192Y

[Paper-level Aggregated] PMCID: PMC3366948

Evidence Type(s): Oncogenic

Summary: Mutation: A572T | Summary: The A572T mutation in JAK3 is described as a somatic mutation that contributes to tumor development, as it was detected in T-ALL and associated with leukemia induction in mice.

Evidence Type: Oncogenic Mutation: M511I | Summary: The M511I mutation in JAK3 is a somatic mutation that has been previously associated with AML and has been shown to transform IL3 dependent cells and induce T-ALL in mice.

Evidence Type: Oncogenic Mutation: A572V | Summary: The A572V mutation in JAK3 is noted to be a somatic variant that has been implicated in T-cell leukemia, T-cell lymphoma, and AML, contributing to tumor development by transforming hematopoietic cells and inducing leukemia in mice.

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

Evidence Type: Oncogenic Mutation: R1027H | Summary: The R1027H variant was present in all analyzed samples, but the data suggest that it may not represent an oncogenic event important for leukemia development in vivo.

Gene→Variant (gene-first): JAK3(3718):A572T JAK3(3718):M511I JAK3(3718):A572V TET1(80312):H1297Y TYK2(7297):R1027H

Genes: JAK3(3718) TET1(80312) TYK2(7297)

Variants: A572T M511I A572V H1297Y R1027H

[Paper-level Aggregated] PMCID: PMC3293822

Evidence Type(s): Functional

Summary: Mutation: A234 | Summary: The mutation A234 is located within a highly conserved motif, suggesting a possible role in the mechanics of AR function. The A234T mutation is located at a critical site affecting function, contributing to loss of transactivational ability.

Evidence Type: Functional Mutation: D221 | Summary: The mutation D221 is implicated in prostate cancer (PCa) and is present in at least four species, indicating a potential impact on AR function. The D221H mutation is associated with loss of function, indicating an alteration in molecular or biochemical function.

Evidence Type: Functional Mutation: E198 | Summary: The mutation E198 is part of a group of amino acids implicated in PCa and is present in multiple species, suggesting its relevance to AR function. The E198G mutation shows a significant reduction in function (50% at 1 nM), indicating an alteration in molecular or biochemical function.

Evidence Type: Functional Mutation: G142 | Summary: The mutation G142 is included in the analysis of amino acids implicated in PCa, indicating its potential role in AR function. The G142V mutation demonstrates constitutive transactivational activity, indicating that it alters molecular function related to regulatory element binding.

Evidence Type: Functional Mutation: G166 | Summary: The mutation G166 is part of the residues examined for their role in prostate cancer, suggesting its involvement in AR function. The G166S mutation showed the least variance from the unmutated receptor, indicating a potential alteration in molecular function.

Evidence Type: Functional Mutation: L57 | Summary: The mutation L57 is implicated in prostate cancer and is present in multiple species, indicating its potential role in AR function. The L57Q mutation exhibited loss of function at all concentrations of DHT, indicating an alteration in molecular function.

Evidence Type: Functional Mutation: M523 | Summary: The mutation M523 is mentioned as being present in at least four species, suggesting its relevance to the mechanics of AR function. The M523V mutation shows constitutive transactivational activity, indicating an alteration in molecular function associated with regulatory element binding.

Evidence Type: Functional Mutation: M537 | Summary: The mutation M537 is included in the analysis of amino acids implicated in PCa, indicating its potential role in AR function. The M537R exhibited a 23% gain of function at 0.1 nM DHT, suggesting an alteration in molecular function, particularly in a low androgen environment. The M537V mutation displays constitutive transactivational activity, suggesting it affects molecular function related to regulatory element binding.

Evidence Type: Functional Mutation: P269 | Summary: The mutation P269 is located within a highly conserved motif associated with prostate cancer, suggesting its relevance to AR function. The P269S mutation is reported to have transactivational activity comparable to wild-type when stimulated by ART-27, suggesting it alters molecular function.

Evidence Type: Functional Mutation: P340 | Summary: The mutation P340 is part of the residues implicated in prostate cancer, indicating its potential role in AR function. The P340L mutation is associated with loss of function and is noted to be present in AIS, indicating an alteration in molecular or biochemical function.

Evidence Type: Functional Mutation: P390 | Summary: The mutation P390 is located within a highly conserved motif, suggesting a possible role in the mechanics of AR function. The P390L mutation acquired a 26% gain of function at 10 nM DHT, suggesting it alters molecular function related to AR signaling.

Evidence Type: Functional Mutation: P514 | Summary: The mutation P514 is mentioned as being present in at least four species, indicating its relevance to the mechanics of AR function. The P514S mutation acquired a 30% gain of function at 10 nM DHT, indicating it alters molecular function in the context of AR signaling.

Evidence Type: Functional Mutation: P515 | Summary: The mutation P515 is included in the analysis of amino acids implicated in PCa, indicating its potential role in AR function.

Evidence Type: Functional Mutation: G524 | Summary: The mutation G524 is part of the residues examined for their role in prostate cancer, suggesting its involvement in AR function. The G524D mutation exhibits constitutive transactivational activity, suggesting it modifies molecular function in the context of regulatory element binding.

Evidence Type: Functional Mutation: S296 | Summary: The mutation S296 is one of the two mutated residues found only in humans, indicating its potential significance in AR function. The S296R mutation alters interaction with the co-repressor N-CoR, leading to reduced transactivational activity, indicating a change in molecular function.

Evidence Type: Functional Mutation: S334 | Summary: The mutation S334 is confined to mammals and is implicated in prostate cancer, suggesting its potential role in AR function. The S334P mutation is associated with loss of function, indicating an alteration in molecular or biochemical function.

Evidence Type: Functional Mutation: P533 | Summary: The mutation P533 is one of the two residues confined to mammals, indicating its potential significance in AR function. The P533S mutation showed a transition from wild-type activity to gain of function, indicating an alteration in molecular function.

Evidence Type: Functional Mutation: T575 | Summary: The mutation T575 is mentioned in the context of a functionally distinct domain of the androgen receptor, indicating its potential role in altering molecular function. The T575A mutation exhibits a loss of function at low DHT concentrations and a significant gain of function at 10 nM, demonstrating its impact on molecular activity.

Evidence Type: Functional Mutation: R629 | Summary: The mutation R629 is highlighted as a highly conserved amino acid, suggesting its importance in the molecular function of the androgen receptor. The R629Q mutation shows a loss of function at low DHT concentrations and a substantial gain of function at 10 nM, indicating its role in altering molecular function.

Evidence Type: Functional Mutation: I672 | Summary: The mutation I672 is also noted as a highly conserved amino acid, indicating its potential role in the molecular function of the androgen receptor. The I672T mutation shows a gain of function at 10 nM DHT and a loss of function at 1 nM, indicating its influence on ligand binding and molecular function.

Evidence Type: Functional Mutation: A586 | Summary: The A586V mutation transitions from a loss of function at low DHT concentrations to a remarkable gain of function at 10 nM, highlighting its significant effect on transactivational activity.

Evidence Type: Functional Mutation: A587 | Summary: The A587S mutation displays constitutive transactivational activity with modest gains of function across all DHT levels, indicating its influence on molecular function.

Evidence Type: Functional Mutation: M886 | Summary: The M886I mutation alters the interaction of the androgen receptor (AR) with co-activators and co-repressors, affecting transactivation ability in prostate cancer. The M886V mutation is part of a group of loss-of-function mutations that exhibit impaired binding to co-regulatory proteins, indicating an alteration in molecular function.

Evidence Type: Functional Mutation: A748 | Summary: The A748V mutation is associated with loss of transactivational activity at physiological levels of DHT, indicating an alteration in molecular function.

Evidence Type: Functional Mutation: A765 | Summary: The A765T mutation is part of a group of loss-of-function mutations that exhibit essentially no transactivational activity at physiological levels of DHT, suggesting a change in molecular function.

Evidence Type: Functional Mutation: L744 | Summary: The L744F mutation is identified as a loss-of-function mutation with no transactivational activity at physiological levels of DHT, indicating an alteration in molecular function.

Evidence Type: Functional Mutation: M749 | Summary: The M749I mutation is classified as a loss-of-function mutation with no transactivational activity at physiological levels of DHT, suggesting a change in molecular function. The M749I mutation exhibits a constitutive gain of function, suggesting it alters molecular function in the context of androgen response.

Evidence Type: Functional Mutation: N756 | Summary: The N756 mutation may be involved in AR dimerization, and its mutation to aspartate resulted in complete loss of function. The N756D mutation is associated with loss of transactivational activity at physiological levels of DHT, indicating an alteration in molecular function.

Evidence Type: Functional Mutation: S759 | Summary: The S759P mutation is part of a group of loss-of-function mutations that exhibit no transactivational activity at physiological levels of DHT, suggesting a change in molecular function.

Evidence Type: Functional Mutation: Y763 | Summary: The Y763C mutation is associated with loss of transactivational activity at physiological levels of DHT, indicating an alteration in molecular function.

Evidence Type: Functional Mutation: K720 | Summary: The K720E mutation is part of a group of mutations showing a distinctive greater loss of function at 1 nM DHT, indicating an alteration in molecular function.

Evidence Type: Functional Mutation: V757 | Summary: The V757A mutation shows a modest loss of function at all levels of DHT, indicating an alteration in molecular function. The V757I mutation is associated with a distinctive greater loss of function at 1 nM DHT, indicating an alteration in molecular function.

Evidence Type: Functional Mutation: Q798 | Summary: The Q798E mutation shows impaired binding to co-regulatory proteins and is associated with a distinctive greater loss of function at 1 nM DHT, indicating an alteration in molecular function. The Q798E mutation shows a modest loss of function at low DHT levels but gains constitutive activity at higher levels, indicating an alteration in molecular function.

Evidence Type: Functional Mutation: Q902 | Summary: The Q902 residue is part of an H-bonding network, and its mutation to arginine (Q902R) may disrupt this interaction, indicating a functional alteration.

Evidence Type: Functional Mutation: D879 | Summary: The D879G mutation is associated with a loss to gain of function, indicating that it alters molecular or biochemical function, with a modest recovery of function at high concentrations of DHT.

Evidence Type: Functional Mutation: Q919 | Summary: The Q919R mutation is described as part of a loss to gain of function, suggesting it alters molecular or biochemical function, although specific details on its activity are not provided.

Evidence Type: Functional Mutation: H874 | Summary: The H874Y mutation exhibits constitutive activity and displays loss of function relative to wild type (WT) at higher levels of DHT, indicating an alteration in molecular function. The H874Y mutation exhibits increased constitutive activity and notable gains of function, indicating a change in molecular function that may influence receptor signaling.

Evidence Type: Functional Mutation: T877 | Summary: The T877A mutation shows a significant constitutive gain of function with a 625% increase in activity compared to WT, indicating a substantial alteration in molecular or biochemical function.

Gene→Variant (gene-first): CREBBP(1387):A234 AKT1(207):D221 AR(367):E198 FDXR(2232):G142 AR(367):G166 AR(367):L57 AR(367):M523 AR(367):M537 AR(367):P269 FDXR(2232):P340 AR(367):P390 AR(367):P514 MYBBP1A(10514):P515 AR(367):G524 AR(367):S296 AR(367):S334 AR(367):P533 NCOA2(10499):T575 NCOA2(10499):R629 NR3C1(2908):I672 NA:A586 NA:A587 NCOR1(9611):M886 NA:A748 NA:A765 NA:L744 CREBBP(1387):M749 AR(367):N756 NA:S759 NA:Y763 NA:K720 NA:V757 NA:Q798 AR(367):Q902 NA:D879 NA:Q919 NA:H874 NA:T877

Genes: CREBBP(1387) AKT1(207) AR(367) FDXR(2232) MYBBP1A(10514) NCOA2(10499) NR3C1(2908) NA NCOR1(9611)

Variants: A234 D221 E198 G142 G166 L57 M523 M537 P269 P340 P390 P514 P515 G524 S296 S334 P533 T575 R629 I672 A586 A587 M886 A748 A765 L744 M749 N756 S759 Y763 K720 V757 Q798 Q902 D879 Q919 H874 T877

[Paper-level Aggregated] PMCID: PMC3293822

Evidence Type(s): Oncogenic

Summary: Mutation: D221H | Summary: The D221H mutation is associated with a loss of function that may contribute to tumor development or progression, as indicated by its context in prostate cancer.

Evidence Type: Oncogenic Mutation: D528G | Summary: The D528G mutation is implicated in tumor development or progression, as suggested by its context in prostate cancer.

Evidence Type: Oncogenic Mutation: P340L | Summary: The P340L mutation exemplifies a loss of function that can drive prostate cancer progression through reduced growth suppression, indicating its oncogenic potential.

Evidence Type: Oncogenic Mutation: G142V | Summary: The G142V mutation shows constitutive activity in the absence of ligand and modest gain of function at all concentrations of DHT, suggesting it contributes to tumor development.

Evidence Type: Oncogenic Mutation: M523V | Summary: The M523V mutation exhibits constitutive activity in the absence of ligand and modest gain of function at all concentrations of DHT, indicating its role in tumor progression.

Evidence Type: Oncogenic Mutation: G524D | Summary: The G524D mutation demonstrates constitutive activity in the absence of ligand and modest gain of function at all concentrations of DHT, suggesting it contributes to tumor development.

Evidence Type: Oncogenic Mutation: M537V | Summary: The M537V mutation shows constitutive activity in the absence of ligand and modest gain of function at all concentrations of DHT, indicating its role in tumor progression.

Evidence Type: Oncogenic Mutation: K910R | Summary: The K910R mutation is associated with driving prostate cancer (PCa) development, despite showing only minor divergence from wild type (WT) and distinctive losses of function.

Evidence Type: Oncogenic Mutation: R726L | Summary: The R726L mutation contributes to tumor development by impairing binding interactions critical for androgen receptor function.

Evidence Type: Oncogenic Mutation: M749I | Summary: The M749I mutation has been identified in relapsed tumors and may contribute to prostate cancer progression, suggesting its role in tumor development.

Evidence Type: Oncogenic Mutation: Q798E | Summary: The Q798E mutation's constitutive activity could have significant implications for prostate cancer development, suggesting its contribution to tumor progression.

Evidence Type: Oncogenic Mutation: H874Y | Summary: The H874Y mutation is associated with constitutive activity and promiscuous ligand activation, representing a potential driver of prostate cancer progression.

Evidence Type: Oncogenic Mutation: M886I | Summary: The mutation M886I is associated with cancer progression through altered binding to co-repressors or co-regulators, indicating its role in tumor development.

Gene→Variant (gene-first): AKT1(207):D221H AR(367):D528G FDXR(2232):P340L FDXR(2232):G142V AR(367):M523V AR(367):G524D AR(367):M537V AR(367):K910R AR(367):R726L CREBBP(1387):M749I MYBBP1A(10514):Q798E AR(367):H874Y NCOR1(9611):M886I

Genes: AKT1(207) AR(367) FDXR(2232) CREBBP(1387) MYBBP1A(10514) NCOR1(9611)

Variants: D221H D528G P340L G142V M523V G524D M537V K910R R726L M749I Q798E H874Y M886I

[Paper-level Aggregated] PMCID: PMC3293822

Evidence Type(s): Predisposing

Summary: Mutation: K720E | Summary: The K720E mutation is implicated in a 6-fold increased risk of prostate cancer, indicating its role as a predisposing variant.

Evidence Type: Predisposing

Gene→Variant (gene-first): NCOR1(9611):K720E

Genes: NCOR1(9611)

Variants: K720E

[Paper-level Aggregated] PMCID: PMC3288377

Evidence Type(s): Oncogenic

Summary: Mutation: p.K27M | Summary: The p.K27M mutation in H3F3A is identified as a somatic mutation that contributes to tumor development in paediatric diffuse intrinsic pontine gliomas (DIPGs).

Evidence Type: Oncogenic Mutation: p.G34R | Summary: The p.G34R mutation in H3F3A is identified as a somatic mutation that contributes to tumor development in non-brainstem paediatric glioblastomas (non-BS-PGs).

Gene→Variant (gene-first): H3-3B(3021):p.K27M H3-3B(3021):p.G34R

Genes: H3-3B(3021)

Variants: p.K27M p.G34R

[Paper-level Aggregated] PMCID: PMC3287118

Evidence Type(s): Oncogenic

Summary: 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): EGFR(1956):L858R EGFR(1956):T790M EGFR(1956):L861Q EGFR(1956):S768I

Genes: EGFR(1956)

Variants: L858R T790M L861Q S768I

[Paper-level Aggregated] PMCID: PMC3266695

Evidence Type(s): Functional

Summary: Mutation: V600E | Summary: The BRAF(V600E) mutation alters the molecular function of the BRAF protein, affecting its dimerization and signaling activity in the context of RAS activation.

Gene→Variant (gene-first): BRAF(673):V600E

Genes: BRAF(673)

Variants: V600E

[Paper-level Aggregated] PMCID: PMC3266695

Evidence Type(s): Oncogenic

Summary: Mutation: V600E | Summary: The BRAF(V600E) mutation contributes to tumor development and progression in melanoma, demonstrating its oncogenic potential.

Gene→Variant (gene-first): BRAF(673):V600E

Genes: BRAF(673)

Variants: V600E

[Paper-level Aggregated] PMCID: PMC3266695

Evidence Type(s): Predictive

Summary: Mutation: V600E | Summary: The BRAF(V600E) mutation is associated with sensitivity to RAF inhibitors in melanoma, indicating its predictive value for therapeutic response.

Gene→Variant (gene-first): BRAF(673):V600E

Genes: BRAF(673)

Variants: V600E

[Paper-level Aggregated] PMCID: PMC3260002

Evidence Type(s): Oncogenic

Summary: Mutation: R882H | Summary: The R882H mutation in DNMT3A is associated with tumor development or progression in AML patients.

Evidence Type: Oncogenic Mutation: R882C | Summary: The R882C mutation in DNMT3A is associated with tumor development or progression in AML patients.

Evidence Type: Oncogenic Mutation: R882P | Summary: The R882P mutation in DNMT3A is associated with tumor development or progression in AML patients.

Evidence Type: Oncogenic Mutation: W893S | Summary: The W893S mutation in DNMT3A is associated with tumor development or progression in AML patients.

Gene→Variant (gene-first): DNMT3A(1788):R882H DNMT3A(1788):R882C DNMT3A(1788):R882P DNMT3A(1788):W893S

Genes: DNMT3A(1788)

Variants: R882H R882C R882P W893S

[Paper-level Aggregated] PMCID: PMC3244026

Evidence Type(s): Functional

Summary: Mutation: Y103fs | Summary: The Y103fs mutation leads to the expression of N-terminal truncated protein products and results in a functionally inactive ETV6 mutant, with no transcriptional repression activity and exhibiting dominant-negative activity compared to wild-type ETV6.

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, leading to a functionally inactive ETV6 mutant that shows no transcriptional repression activity and exhibits dominant-negative activity compared to wild-type ETV6.

Evidence Type: Functional Mutation: V345fs | Summary: The V345fs mutation causes the expression of C-terminal truncated polypeptides, resulting in a functionally inactive ETV6 mutant that shows no transcriptional repression activity and exhibits dominant-negative activity compared to wild-type ETV6.

Evidence Type: Functional Mutation: N356fs | Summary: The N356fs mutation results in the expression of C-terminal truncated ETV6 proteins, leading to a functionally inactive ETV6 mutant that demonstrates a lack of transcriptional repression activity and exhibits dominant-negative activity compared to wild-type ETV6.

Gene→Variant (gene-first): ETV6(2120):Y103fs ETV6(2120):S105fs ETV6(2120):V345fs ETV6(2120):N356fs

Genes: ETV6(2120)

Variants: Y103fs S105fs V345fs N356fs

[Paper-level Aggregated] PMCID: PMC3219854

Evidence Type(s): Functional

Summary: Mutation: Trp557Gly | Summary: The Trp557Gly mutation alters the molecular function of the KIT protein, which is implicated in the pathogenesis of neurofibromatosis type 1-related gastrointestinal stromal tumors (GISTs).

Gene→Variant (gene-first): KIT(3815):Trp557Gly

Genes: KIT(3815)

Variants: Trp557Gly

[Paper-level Aggregated] PMCID: PMC3219854

Evidence Type(s): Oncogenic

Summary: Mutation: Trp557Gly | Summary: The Trp557Gly mutation in KIT is identified as a missense point mutation associated with neurofibromatosis type 1-related gastrointestinal stromal tumors (GISTs), indicating its contribution to tumor development.

Gene→Variant (gene-first): KIT(3815):Trp557Gly

Genes: KIT(3815)

Variants: Trp557Gly