[Paper-level Aggregated] PMCID: PMC12221223

Evidence Type(s): Oncogenic

Summary: Mutation: C>T | Summary: The C>T mutation contributes to tumor development in the context of NF1Mut melanomas, indicating its role as an oncogenic variant.

Gene→Variant (gene-first): NF1(4763):C>T

Genes: NF1(4763)

Variants: C>T

[Paper-level Aggregated] PMCID: PMC12221223

Evidence Type(s): Diagnostic

Summary: Mutation: C>T | Summary: The C>T mutation is characterized as a well-established feature defining cutaneous melanoma, indicating its role in classifying the disease.

Gene→Variant (gene-first): NF1(4763):C>T

Genes: NF1(4763)

Variants: C>T

[Paper-level Aggregated] PMCID: PMC11551396

Evidence Type(s): Functional

Summary: Mutation: N771insSVD | Summary: The N771insSVD variant alters the molecular function of EGFR, as it is involved in drug sensitivity and resistance mechanisms compared to wild-type EGFR.

Evidence Type: Functional Mutation: L858R | Summary: The L858R mutation alters the enzyme kinetic parameters of EGFR, demonstrating a significant increase in catalytic efficiency compared to wild-type EGFR.

Evidence Type: Functional Mutation: T790M | Summary: The T790M mutation is associated with altered enzyme kinetics, showing increased catalytic rates compared to wild-type EGFR, and is also studied in the context of cocrystal structures with various inhibitors, indicating an alteration in molecular or biochemical function.

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

Evidence Type: Functional Mutation: C797 | Summary: The C797 mutation forms a covalent bond with the inhibitor, indicating an alteration in molecular function related to drug binding.

Gene→Variant (gene-first): EGFR(1956):N771insSVD EGFR(1956):L858R EGFR(1956):T790M EGFR(1956):V948R EGFR(1956):C797

Genes: EGFR(1956)

Variants: N771insSVD L858R T790M V948R C797

[Paper-level Aggregated] PMCID: PMC11551396

Evidence Type(s): Oncogenic

Summary: Mutation: L858R | Summary: The L858R mutation contributes to tumor development or progression, as indicated by its enhanced catalytic rates and sensitivity compared to other variants, and is associated with enhanced sensitivity to inhibitors compared to wild-type EGFR.

Evidence Type: Oncogenic Mutation: T790 | Summary: The T790 mutation is associated with tumor development or progression, as it is a gatekeeper residue involved in resistance mechanisms and is linked to the binding of TAK-788, indicating its role through interaction with therapeutic agents.

Evidence Type: Oncogenic Mutation: T790M | Summary: The T790M mutation is associated with an inactive kinase conformation, contributing to tumor development or progression.

Evidence Type: Oncogenic Mutation: V948R | Summary: The V948R mutation prevents the formation of the activating asymmetric dimer interaction, indicating its role in tumor development or progression.

Gene→Variant (gene-first): EGFR(1956):L858R EGFR(1956):T790 EGFR(1956):T790M EGFR(1956):V948R

Genes: EGFR(1956)

Variants: L858R T790 T790M V948R

[Paper-level Aggregated] PMCID: PMC11551396

Evidence Type(s): Predictive

Summary: Mutation: L858R | Summary: The L858R mutation is associated with a lack of sensitivity to 1st-3rd generation EGFR tyrosine kinase inhibitors (TKIs) and shows a drug-sensitizing effect, correlating with greater potency against L858R EGFR compared to wild-type EGFR. It is evaluated for its response to a diverse panel of EGFR inhibitors, indicating its potential role in predicting treatment sensitivity or resistance.

Evidence Type: Predictive Mutation: N771insSVD | Summary: The N771insSVD variant shows a lack of sensitivity to 1st-3rd generation EGFR TKIs, suggesting its predictive role in therapy response.

Evidence Type: Predictive Mutation: T790M | Summary: The T790M mutation is included in the evaluation of biochemical potencies against EGFR inhibitors, suggesting its relevance in predicting treatment response or resistance.

Gene→Variant (gene-first): EGFR(1956):L858R EGFR(1956):N771insSVD EGFR(1956):T790M

Genes: EGFR(1956)

Variants: L858R N771insSVD T790M

[Paper-level Aggregated] PMCID: PMC11272140

Evidence Type(s): Oncogenic

Summary: Mutation: G2032R | Summary: The G2032R mutation contributes to tumor development or progression in the context of ROS1+ non-small cell lung cancer and is identified as a ROS1 resistance mutation in crizotinib-pretreated patients, suggesting its role in tumor progression and resistance to therapy.

Evidence Type: Oncogenic Mutation: L2026M | Summary: The L2026M mutation is noted as a ROS1 resistance mutation in crizotinib-pretreated patients, contributing to tumor development and resistance.

Evidence Type: Oncogenic Mutation: S1986F | Summary: The S1986F mutation is classified as a ROS1 resistance mutation in crizotinib-pretreated patients, suggesting its involvement in tumor progression and resistance mechanisms.

Evidence Type: Oncogenic Mutation: G2101A | Summary: The G2101A mutation, detected in a patient with crizotinib resistance, is implicated in tumor development and progression as a ROS1 resistance mutation.

Gene→Variant (gene-first): ROS1(6098):G2032R TXK(7294):L2026M TXK(7294):S1986F NTRK1(4914):G2101A

Genes: ROS1(6098) TXK(7294) NTRK1(4914)

Variants: G2032R L2026M S1986F G2101A

[Paper-level Aggregated] PMCID: PMC11272140

Evidence Type(s): Predictive

Summary: Mutation: G2032R | Summary: The G2032R mutation is associated with a favorable response to taletrectinib, indicating a predictive value for treatment response in ROS1+ non-small cell lung cancer, with a response rate of 67% in patients. Additionally, it is linked to acquired resistance to therapy, highlighting its relevance in predicting treatment outcomes and sensitivity to taletrectinib.

Gene→Variant (gene-first): ROS1(6098):G2032R

Genes: ROS1(6098)

Variants: G2032R

[Paper-level Aggregated] PMCID: PMC11253285

Evidence Type(s): Functional

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

Gene→Variant (gene-first): PARP1(142):S4D

Genes: PARP1(142)

Variants: S4D

[Paper-level Aggregated] PMCID: PMC11253285

Evidence Type(s): Predictive

Summary: Mutation: S4D | Summary: The S4D mutation is associated with a response to SRA737 in combination with PARP inhibitors, indicating its potential predictive value for therapy response.

Gene→Variant (gene-first): PARP1(142):S4D

Genes: PARP1(142)

Variants: S4D

[Paper-level Aggregated] PMCID: PMC10805385

Evidence Type(s): Oncogenic

Summary: Mutation: G12C | Summary: The G12C mutation in KRAS is associated with tumor development, as indicated by its presence in primary KRAS-mutant tumors and patient-derived xenograft models.

Evidence Type: Oncogenic Mutation: G245V | Summary: The G245V mutation in TP53 is present in a KRAS-mutant tumor context, suggesting its contribution to tumor development and progression in the analyzed patient-derived xenograft models.

Gene→Variant (gene-first): KRAS(3845):G12C TP53(7157):G245V

Genes: KRAS(3845) TP53(7157)

Variants: G12C G245V

[Paper-level Aggregated] PMCID: PMC10690049

Evidence Type(s): Oncogenic

Summary: Mutation: G12C | Summary: The KRAS G12C mutation contributes to tumor development and progression, as indicated by its presence in various cancer cell lines and the observed effects of targeted therapies.

Evidence Type: Oncogenic Mutation: G12D | Summary: The KRAS G12D mutation is associated with tumor development or progression, as it is mentioned in the context of MEFs that are used to study cancer behavior.

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

Genes: KRAS(3845)

Variants: G12C G12D

[Paper-level Aggregated] PMCID: PMC10690049

Evidence Type(s): Predictive

Summary: Mutation: G12C | Summary: The KRAS G12C mutation is associated with sensitivity to specific therapies, demonstrated by the synergistic inhibition of cell proliferation in KRAS G12C-mutant cell lines treated with MRTX849/AMG510 and KPT9274.

Evidence Type: Predictive Mutation: G12D | Summary: The KRAS G12D mutation was tested in the context of a drug combination, indicating a potential correlation with resistance to therapy, as the KRAS G12D MEFs were refractory to growth inhibition.

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

Genes: KRAS(3845)

Variants: G12C G12D

[Paper-level Aggregated] PMCID: PMC10618648

Evidence Type(s): Oncogenic

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

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

Evidence Type: Oncogenic Mutation: T733I | Summary: The ERBB2 T733I mutation is noted to be weakly transforming in a gastroesophageal PDX model, indicating its contribution to tumor development.

Gene→Variant (gene-first): ERBB2(2064):V777L ERBB2(2064):G778A ERBB2(2064):T733I

Genes: ERBB2(2064)

Variants: V777L G778A T733I

[Paper-level Aggregated] PMCID: PMC10618648

Evidence Type(s): Predictive

Summary: Mutation: T733I | Summary: The T733I mutation is associated with resistance to lapatinib and sensitivity to adavosertib, suggesting its role in predicting treatment response.

Gene→Variant (gene-first): ERBB2(2064):T733I

Genes: ERBB2(2064)

Variants: T733I

[Paper-level Aggregated] PMCID: PMC10527017

Evidence Type(s): Functional

Summary: Mutation: V777L | Summary: The HER2V777L mutation alters the invasive phenotype of breast tumor cells and molecular function by enhancing the phosphorylation of key proteins involved in cell cycle regulation. This is indicated by changes in phosphorylation levels and gene expression in breast cancer organoids, as well as the metastatic behavior observed in vitro and in vivo.

Gene→Variant (gene-first): ERBB2(2064):V777L

Genes: ERBB2(2064)

Variants: V777L

[Paper-level Aggregated] PMCID: PMC10527017

Evidence Type(s): Oncogenic

Summary: Mutation: V777L | Summary: The HER2 V777L mutation is associated with tumor development and progression in breast cancer, as evidenced by its role in tumor formation in transgenic mice, enhanced cellular migration and invasion in breast organoids, and its contribution to lung metastases. It promotes cell proliferation and alters signaling pathways, leading to increased oncogene expression and tumorigenesis. The mutation is implicated in distinct expression programs related to cancer and is linked to resistance to the pan-HER tyrosine kinase inhibitor neratinib.

Evidence Type: Oncogenic Mutation: H1047R | Summary: The PIK3CA H1047R mutation is described as a gain-of-function allele commonly found in human breast cancers, indicating its role in tumor development and progression, particularly in specific cancer subtypes.

Gene→Variant (gene-first): ERBB2(2064):V777L PIK3CA(5290):H1047R

Genes: ERBB2(2064) PIK3CA(5290)

Variants: V777L H1047R

[Paper-level Aggregated] PMCID: PMC10527017

Evidence Type(s): Diagnostic

Summary: Mutation: H1047R | Summary: The H1047R mutation is used to classify tumors into specific subtypes, such as Luminal A and B, based on PAM50 classification, indicating its role in defining disease characteristics.

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

Genes: PIK3CA(5290)

Variants: H1047R

[Paper-level Aggregated] PMCID: PMC10527017

Evidence Type(s): Predictive

Summary: Mutation: V777L | Summary: The HER2V777L mutation is associated with resistance to the pan-HER tyrosine kinase inhibitor neratinib, indicating its predictive value for therapy response.

Gene→Variant (gene-first): ERBB2(2064):V777L

Genes: ERBB2(2064)

Variants: V777L

[Paper-level Aggregated] PMCID: PMC10524391

Evidence Type(s): Oncogenic

Summary: Mutation: T790M | Summary: The T790M mutation is associated with tumor development and progression, contributing to resistance in EGFR-mutant lung cancers and recognized as an oncogenic variant in the context of acquired resistance to EGFR-targeted therapies.

Evidence Type: Oncogenic Mutation: L858R | Summary: The L858R mutation is implicated in tumor development, as it is present in tumors alongside other mutations.

Evidence Type: Oncogenic Mutation: L747S | Summary: The L747S mutation is associated with tumor development, as it is found in a tumor with concurrent mutations.

Evidence Type: Oncogenic Mutation: C797S | Summary: The C797S mutation contributes to tumor development or progression as a resistance mutation in EGFR, particularly in the context of EGFR-mutant lung cancers.

Evidence Type: Oncogenic Mutation: V804M | Summary: The RET V804M mutation is linked to tumor development, supporting its classification as an oncogenic variant.

Evidence Type: Oncogenic Mutation: V804E | Summary: The RET V804E mutation is associated with tumor development, indicating its role as an oncogenic driver.

Evidence Type: Oncogenic Mutation: G810S | Summary: The RET G810S mutation is associated with tumor progression, reinforcing its role as an oncogenic driver in RET fusion-positive lung cancers.

Evidence Type: Oncogenic Mutation: G12S | Summary: The KRAS G12S mutation is associated with tumor development or progression, recognized for its contribution to tumor development as part of off-target resistance mechanisms.

Evidence Type: Oncogenic Mutation: V600E | Summary: The BRAF V600E mutation is identified as a hotspot mutation contributing to tumor development or progression, recognized for its role in tumor progression as part of off-target resistance mechanisms.

Gene→Variant (gene-first): EGFR(1956):T790M EGFR(1956):L858R EGFR(1956):L747S EGFR(1956):C797S RET(5979):V804M RET(5979):V804E RET(5979):G810S KRAS(3845):G12S BRAF(673):V600E

Genes: EGFR(1956) RET(5979) KRAS(3845) BRAF(673)

Variants: T790M L858R L747S C797S V804M V804E G810S G12S V600E

[Paper-level Aggregated] PMCID: PMC10524391

Evidence Type(s): Predictive

Summary: Mutation: T790M | Summary: The EGFR T790M mutation is associated with resistance to earlier generation EGFR TKIs and therapeutic EGFR engagement, indicating its predictive role in therapy response when patients are treated with osimertinib.

Evidence Type: Predictive Mutation: C797S | Summary: The C797S mutation is associated with resistance mechanisms and therapeutic EGFR engagement, indicating its potential role in treatment response, including resistance to osimertinib.

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

Genes: EGFR(1956)

Variants: T790M C797S

[Paper-level Aggregated] PMCID: PMC10390864

Evidence Type(s): Functional

Summary: Mutation: A126T | Summary: The A126T mutation was assessed in a cell-based HDR assay, indicating its influence on RAD51C HR DNA repair activity. It is described as a neutral variant that coimmunoprecipitates with RAD51D and XRCC2, indicating it does not alter the molecular function of the RAD51C complexes.

Evidence Type: Functional Mutation: C135Y | Summary: The C135Y mutation was categorized as deleterious in the HDR assay, demonstrating its impact on RAD51C HR DNA repair activity. It introduces a charged or bulky group into a tight hydrophobic pocket, potentially destabilizing the residue 130-140 helical region and influencing RAD51C function. Additionally, it exhibits dramatically reduced RAD51 foci formation, indicating it alters molecular function related to DNA damage response.

Evidence Type: Functional Mutation: D109Y | Summary: The D109Y variant induces RAD51 foci formation, indicating it alters molecular function related to DNA damage response. It is also a neutral variant that coimmunoprecipitates with RAD51D and XRCC2, suggesting it does not affect the molecular function of the RAD51C complexes.

Evidence Type: Functional Mutation: D159N | Summary: The D159N mutation was classified as intermediate in the HDR assay, suggesting it alters RAD51C HR DNA repair activity. It is classified as an intermediate variant that loses the ability to bind to XRCC3 but retains binding to RAD51D-XRCC2, indicating a change in molecular function.

Evidence Type: Functional Mutation: G125V | Summary: The G125V mutation was identified as deleterious in the HDR assay, indicating its effect on RAD51C HR DNA repair activity.

Evidence Type: Functional Mutation: G130R | Summary: The G130R variant was confirmed to have functional effects in a human cell line, indicating it alters molecular or biochemical function. It introduces a charged or bulky group into a tight hydrophobic pocket, potentially destabilizing the residue 130-140 helical region and influencing RAD51C function. Additionally, it alters molecular function by causing a significant decrease in RAD51 foci, indicating a disruption in homologous recombination repair.

Evidence Type: Functional Mutation: G153D | Summary: The G153D mutation was categorized as deleterious in the HDR assay, reflecting its influence on RAD51C HR DNA repair activity.

Evidence Type: Functional Mutation: G162E | Summary: The G162E variant is identified as a deleterious variant that loses the ability to bind to XRCC3 but can still bind to RAD51D-XRCC2, indicating an alteration in molecular function.

Evidence Type: Functional Mutation: G264S | Summary: The G264S mutation was classified as neutral in the HDR assay, indicating it does not significantly alter RAD51C HR DNA repair activity.

Evidence Type: Functional Mutation: G264V | Summary: The G264V mutation was categorized as neutral in the HDR assay, suggesting it does not impact RAD51C HR DNA repair activity.

Evidence Type: Functional Mutation: G306R | Summary: The variant p.Gly306Arg (G306R) exhibits altered IC50 values for cisplatin and olaparib, suggesting a functional impact on drug response. It also exhibits partially reduced RAD51 foci formation, indicating it alters molecular function related to DNA damage response.

Evidence Type: Functional Mutation: K131I | Summary: The K131I variant was confirmed to have functional effects in a human cell line, indicating it alters molecular or biochemical function. It leads to a significant decrease in RAD51 foci, which suggests a disruption in homologous recombination repair.

Evidence Type: Functional Mutation: L138F | Summary: The L138F variant is characterized as deleterious and shows reduced HDR activity in U2OS cells, indicating that it alters molecular function related to homologous recombination. It introduces a charged or bulky group into a tight hydrophobic pocket, potentially destabilizing the residue 130-140 helical region and influencing RAD51C function. Additionally, it alters molecular function, as evidenced by a decrease in RAD51 foci, suggesting a disruption in homologous recombination repair.

Evidence Type: Functional Mutation: L219S | Summary: The L219S mutation was classified as neutral in the HDR assay, indicating it does not significantly alter RAD51C HR DNA repair activity.

Evidence Type: Functional Mutation: P21S | Summary: The P21S variant induces RAD51 foci formation, indicating it alters molecular function related to DNA damage response.

Evidence Type: Functional Mutation: R168G | Summary: The R168G variant was confirmed to have functional effects in a human cell line, indicating it alters molecular or biochemical function. It impacts molecular function, leading to a significant decrease in RAD51 foci, indicating a disruption in homologous recombination repair. It also removes a positively charged residue that directly interacts with the negatively charged triphosphate group of ATP, influencing RAD51C function.

Evidence Type: Functional Mutation: R214C | Summary: The R214C mutation was reported as neutral in the HDR assay, indicating it does not affect RAD51C HR DNA repair activity.

Evidence Type: Functional Mutation: R258H | Summary: The R258H variant, observed as a homozygous variant in a FANCO patient, displays reduced binding for all complex members, indicating a change in molecular function. It was classified as intermediate in the HDR assay, suggesting it alters RAD51C HR DNA repair activity.

Evidence Type: Functional Mutation: R312W | Summary: The R312W variant was identified as deleterious in the HDR assay, demonstrating its effect on RAD51C HR DNA repair activity. It removes a positively charged residue that may weaken the interaction with the negatively charged gamma phosphate group of ATP, influencing RAD51C activity.

Evidence Type: Functional Mutation: T132R | Summary: The T132R variant was confirmed to have functional effects in a human cell line, indicating it alters molecular or biochemical function. It affects molecular function, resulting in a significant decrease in RAD51 foci, indicating a disruption in homologous recombination repair. It introduces a charged or bulky group into a tight hydrophobic pocket, potentially destabilizing the residue 130-140 helical region and influencing RAD51C function.

Evidence Type: Functional Mutation: T287A | Summary: The T287A mutation was categorized as neutral in the HDR assay, suggesting it does not impact RAD51C HR DNA repair activity.

Evidence Type: Functional Mutation: V140E | Summary: The V140E variant exhibits dramatically reduced RAD51 foci formation, indicating it alters molecular function related to DNA damage response. It introduces a charged or bulky group into a tight hydrophobic pocket, potentially destabilizing the residue 130-140 helical region and influencing RAD51C function.

Evidence Type: Functional Mutation: G302V | Summary: The G302V variant was confirmed to have functional effects in a human cell line, indicating it alters molecular or biochemical function. It is identified as a deleterious variant that loses the ability to bind to XRCC3 but can still bind to RAD51D-XRCC2, indicating an alteration in molecular function. It disrupts a hydrophobic core and may interfere with RAD51C protomer formation, influencing RAD51C function.

Evidence Type: Functional Mutation: T336P | Summary: The T336P variant is a deleterious variant that binds only to XRCC3 and not to RAD51D-XRCC2, indicating a change in molecular function.

Evidence Type: Functional

Gene→Variant (gene-first): RAD51C(5889):A126T RAD51C(5889):C135Y RAD51C(5889):D109Y RAD51C(5889):D159N RAD51C(5889):G125V RAD51C(5889):G130R RAD51C(5889):G153D RAD51C(5889):G162E RAD51C(5889):G264S RAD51C(5889):G264V RAD51C(5889):G306R RAD51C(5889):K131I RAD51C(5889):L138F RAD51C(5889):L219S RAD51C(5889):P21S RAD51C(5889):R168G RAD51C(5889):R214C RAD51C(5889):R258H RAD51C(5889):R312W RAD51C(5889):T132R RAD51C(5889):T287A RAD51C(5889):V140E RAD51C(5889):G302V RAD51C(5889):T336P

Genes: RAD51C(5889)

Variants: A126T C135Y D109Y D159N G125V G130R G153D G162E G264S G264V G306R K131I L138F L219S P21S R168G R214C R258H R312W T132R T287A V140E G302V T336P

[Paper-level Aggregated] PMCID: PMC10390864

Evidence Type(s): Oncogenic

Summary: Mutation: L138F | Summary: The L138F variant is identified as a deleterious variant that fails to coimmunoprecipitate with RAD51D and XRCC2, indicating its contribution to tumor development or progression.

Gene→Variant (gene-first): RAD51C(5889):L138F

Genes: RAD51C(5889)

Variants: L138F

[Paper-level Aggregated] PMCID: PMC10390864

Evidence Type(s): Predictive

Summary: Mutation: E94K | Summary: The variant p.Glu94Lys (E94K) shows a significant reduction in sensitivity to cisplatin and a notable decrease in sensitivity to olaparib, indicating its potential role in predicting treatment response.

Evidence Type: Predictive Mutation: G306R | Summary: The variant p.Gly306Arg (G306R) demonstrates a marked reduction in sensitivity to both cisplatin and olaparib, suggesting its predictive value for treatment response.

Evidence Type: Predictive Mutation: G130R | Summary: The G130R variant showed sensitivity to olaparib compared with WT-complemented cells, indicating a correlation with response to therapy.

Evidence Type: Predictive Mutation: K131I | Summary: The K131I variant showed sensitivity to olaparib compared with WT-complemented cells, indicating a correlation with response to therapy.

Evidence Type: Predictive Mutation: T132R | Summary: The T132R variant showed sensitivity to olaparib compared with WT-complemented cells, indicating a correlation with response to therapy.

Evidence Type: Predictive Mutation: Q133E | Summary: The Q133E variant had intermediate effects on sensitivity to olaparib compared with WT-complemented cells, indicating a correlation with response to therapy.

Evidence Type: Predictive Mutation: G302V | Summary: The G302V variant had intermediate effects on sensitivity to olaparib compared with WT-complemented cells, indicating a correlation with response to therapy.

Evidence Type: Predictive Mutation: L138F | Summary: The L138F variant is associated with sensitivity to cisplatin and olaparib in CL-V4B cells, suggesting it may correlate with response to specific therapies.

Gene→Variant (gene-first): RAD51C(5889):E94K RAD51C(5889):G306R RAD51C(5889):G130R RAD51C(5889):K131I RAD51C(5889):T132R RAD51C(5889):Q133E RAD51C(5889):G302V RAD51C(5889):L138F

Genes: RAD51C(5889)

Variants: E94K G306R G130R K131I T132R Q133E G302V L138F

[Paper-level Aggregated] PMCID: PMC10283448

Evidence Type(s): Oncogenic

Summary: Mutation: G2032R | Summary: The G2032R mutation contributes to tumor progression in ROS1+ lung cancer, is implicated in crizotinib resistance, and is part of the CD74-ROS1 rearrangement, highlighting its role as an oncogenic variant and its involvement in tumor development or progression.

Evidence Type: Oncogenic Mutation: 196_197insHP | Summary: The mutation in CEBPA (196_197insHP) was identified in a post-repotrectinib tumor biopsy, suggesting its potential role in tumor development or progression.

Evidence Type: Oncogenic Mutation: E171G | Summary: The TP53 mutation (E171G) was detected in the post-repotrectinib tumor biopsy, indicating its possible contribution to tumor progression.

Evidence Type: Oncogenic Mutation: H178Q | Summary: The TP53 mutation (H178Q) found in the post-repotrectinib tumor biopsy may play a role in tumor development or progression.

Evidence Type: Oncogenic Mutation: H179Y | Summary: The TP53 mutation (H179Y) identified in the post-repotrectinib tumor biopsy suggests its involvement in tumor progression.

Evidence Type: Oncogenic Mutation: H555R | Summary: The RB1 mutation (H555R) detected in the post-repotrectinib tumor biopsy indicates its potential role in tumor development.

Evidence Type: Oncogenic Mutation: R143Q | Summary: The ERBB2 mutation (R143Q) found in the post-repotrectinib tumor biopsy suggests its contribution to tumor progression.

Gene→Variant (gene-first): ROS1(6098):G2032R CEBPA(1050):196_197insHP TP53(7157):E171G ERBB2(2064):H178Q TP53(7157):H179Y RB1(5925):H555R ERBB2(2064):R143Q

Genes: ROS1(6098) CEBPA(1050) TP53(7157) ERBB2(2064) RB1(5925)

Variants: G2032R 196_197insHP E171G H178Q H179Y H555R R143Q

[Paper-level Aggregated] PMCID: PMC10283448

Evidence Type(s): Predictive

Summary: Mutation: G2032R | Summary: The G2032R mutation is associated with resistance to crizotinib treatment in ROS1+ lung cancer and has predictive value for treatment outcomes with various tyrosine kinase inhibitors (TKIs) such as cabozantinib and lorlatinib. It is also linked to a positive response to repotrectinib treatment in patients with ROS1-rearranged NSCLC, indicating its relevance in predicting treatment response.

Gene→Variant (gene-first): ROS1(6098):G2032R

Genes: ROS1(6098)

Variants: G2032R

[Paper-level Aggregated] PMCID: PMC10183391

Evidence Type(s): Oncogenic

Summary: Mutation: c.2262_2264delinsTCC | Summary: The ERBB2 exon 19 c.2262_2264delinsTCC mutation contributes to tumor development or progression in the context of non-small cell lung cancer (NSCLC).

Evidence Type: Oncogenic Mutation: p.L755P | Summary: The p.L755P mutation in HER2 contributes to tumor development or progression in the context of stage IV NSCLC, supporting its classification as an oncogenic variant.

Gene→Variant (gene-first): ERBB2(2064):c.2262_2264delinsTCC ERBB2(2064):p.L755P

Genes: ERBB2(2064)

Variants: c.2262_2264delinsTCC p.L755P

[Paper-level Aggregated] PMCID: PMC10183391

Evidence Type(s): Predictive

Summary: Mutation: c.2262_2264delinsTCC; p.(L755P) | Summary: The ERBB2 exon 19 c.2262_2264delinsTCC; p.(L755P) mutation is associated with a response to osimertinib treatment, indicating its predictive value for therapy effectiveness in patients with stage IV NSCLC.

Evidence Type: Predictive Mutation: p.L755P | Summary: The p.L755P mutation in HER2 is associated with a positive response to osimertinib treatment in patients with NSCLC, suggesting its potential as a predictive biomarker for targeted therapy effectiveness.

Gene→Variant (gene-first): ERBB2(2064):c.2262_2264delinsTCC ERBB2(2064):p.(L755P) ERBB2(2064):p.L755P

Genes: ERBB2(2064)

Variants: c.2262_2264delinsTCC p.(L755P) p.L755P

[Paper-level Aggregated] PMCID: PMC10161095

Evidence Type(s): Functional

Summary: Mutation: lysine-to-methionine | Summary: The H3K27M mutation alters histone modifications, impacting the function of the SWI/SNF complex and leading to changes in chromatin accessibility and gene expression.

Gene→Variant (gene-first): PBRM1(55193):lysine-to-methionine

Genes: PBRM1(55193)

Variants: lysine-to-methionine

[Paper-level Aggregated] PMCID: PMC10161095

Evidence Type(s): Oncogenic

Summary: Mutation: lysine-to-methionine | Summary: The lysine-to-methionine mutation at histone H3 lysine 27 (H3K27M) is associated with the development and progression of diffuse midline gliomas, contributing to the tumor's lethal characteristics.

Gene→Variant (gene-first): PBRM1(55193):lysine-to-methionine

Genes: PBRM1(55193)

Variants: lysine-to-methionine

[Paper-level Aggregated] PMCID: PMC10082285

Evidence Type(s): Diagnostic

Summary: Mutation: L858R | Summary: The presence of the L858R mutation is used to classify and confirm the diagnosis of EGFR-mutated NSCLC, supporting its role as a diagnostic marker.

Evidence Type: Diagnostic

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

Genes: EGFR(1956)

Variants: L858R

[Paper-level Aggregated] PMCID: PMC10082285

Evidence Type(s): Predictive

Summary: Mutation: L858R | Summary: The L858R mutation is associated with response to osimertinib therapy in patients with EGFR-mutated NSCLC, indicating its predictive value for treatment sensitivity.

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

Genes: EGFR(1956)

Variants: L858R

[Paper-level Aggregated] PMCID: PMC10015977

Evidence Type(s): Functional

Summary: Mutation: K700E | Summary: The K700E mutation is associated with distinct alternative splicing events and altered molecular functions in myelodysplastic syndromes (MDS). Splicing analysis suggests that this variant may influence molecular or biochemical functions related to splicing and mRNA processing.

Evidence Type: Functional Mutation: E862K | Summary: The SETBP1 E862K mutation is mentioned in the context of transformation, indicating a potential alteration in molecular function related to disease evolution.

Gene→Variant (gene-first): SF3B1(23451):K700E SETBP1(26040):E862K

Genes: SF3B1(23451) SETBP1(26040)

Variants: K700E E862K

[Paper-level Aggregated] PMCID: PMC10015977

Evidence Type(s): Oncogenic

Summary: Mutation: K700E | Summary: The K700E mutation in SF3B1 is associated with tumor development and progression in myelodysplastic syndromes (MDS). It is noted as the most frequent mutation in patients and contributes to improved overall survival outcomes, indicating its role in tumor development. The mutation influences alternative splicing events and is linked to specific clinical features, including a higher percentage of ring sideroblasts. Additionally, it was acquired during the transformation to AML, further suggesting its involvement in tumor progression.

Evidence Type: Oncogenic Mutation: R625 | Summary: The R625 mutation is part of recurrent non-K700E mutations associated with MDS, suggesting its contribution to tumor development or progression. The R625C variant is specifically associated with clonal evolution in patients with MDS-EB, indicating its role in tumor development.

Evidence Type: Oncogenic

Gene→Variant (gene-first): SF3B1(23451):K700E SF3B1(23451):R625

Genes: SF3B1(23451)

Variants: K700E R625

[Paper-level Aggregated] PMCID: PMC10015977

Evidence Type(s): Prognostic

Summary: Mutation: K700E | Summary: The K700E mutation in SF3B1 is associated with a favorable prognosis in myelodysplastic syndromes (MDS), correlating with significantly better overall survival (OS) outcomes compared to non-K700E mutations and SF3B1 wild-type patients. It is linked to specific clinical features, such as a higher percentage of ring sideroblasts and lower comprehensive cytogenetic scoring system (CCSS) scores, indicating its relevance in predicting disease outcomes. However, some evidence suggests that the K700E mutation may not show significant differences in OS compared to other SF3B1 mutations, indicating variability in its prognostic significance.

Evidence Type: Prognostic Mutation: R625 | Summary: The presence of the R625 mutation, as a recurrent mutation in MDS, may correlate with disease outcomes in patients, independent of therapy.

Gene→Variant (gene-first): SF3B1(23451):K700E SF3B1(23451):R625

Genes: SF3B1(23451)

Variants: K700E R625

[Paper-level Aggregated] PMCID: PMC10015977

Evidence Type(s): Diagnostic

Summary: Mutation: K700E | Summary: The K700E mutation in SF3B1 is important for diagnostic classification in myelodysplastic syndromes (MDS). It is used to refine sub-classification and risk assessment criteria, helping to define disease characteristics and classify patients based on specific clinico-pathologic features and cytogenetic aberrations. The presence of K700E aids in distinguishing between different subtypes of MDS and correlates with certain clinical features, such as a higher percentage of ring sideroblasts and ANC.

Gene→Variant (gene-first): SF3B1(23451):K700E

Genes: SF3B1(23451)

Variants: K700E

[Paper-level Aggregated] PMCID: PMC10011885

Evidence Type(s): Functional

Summary: Mutation: A163G | Summary: The KDR A163G mutation is mentioned in the context of targeted sequencing, suggesting it may alter molecular or biochemical function.

Evidence Type: Functional Mutation: R106H | Summary: The MSH6 R106H mutation is identified in the context of targeted sequencing, indicating a potential alteration in molecular or biochemical function.

Gene→Variant (gene-first): KDR(3791):A163G SLTM(79811):R106H

Genes: KDR(3791) SLTM(79811)

Variants: A163G R106H

[Paper-level Aggregated] PMCID: PMC10011885

Evidence Type(s): Oncogenic

Summary: Mutation: V600E | Summary: The BRAF V600E mutation is associated with tumor development and progression in various cancers, including metastatic colorectal cancer. It contributes to tumor dynamics, is retained during disease progression, and is implicated as an oncogenic driver.

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

Evidence Type: Oncogenic Mutation: Q61H | Summary: The KRAS Q61H mutation is associated with the emergence of subclonal mutations contributing to tumor development and progression, as indicated by its detection prior to disease progression.

Evidence Type: Oncogenic Mutation: Q61L | Summary: The KRAS Q61L mutation is part of multiple subclonal KRAS mutations identified, which are implicated in tumor development and progression.

Evidence Type: Oncogenic Mutation: G12N | Summary: The KRAS G12N mutation is included among the subclonal mutations that contribute to tumor development and progression.

Evidence Type: Oncogenic Mutation: G13D | Summary: The KRAS G13D mutation is identified as a subclonal mutation that plays a role in tumor development and progression.

Evidence Type: Oncogenic Mutation: G12D | Summary: The NRAS G12D mutation is part of the identified mutations that contribute to tumor development and progression.

Gene→Variant (gene-first): BRAF(673):V600E NRAS(4893):G13C KRAS(3845):Q61H NRAS(4893):Q61L KRAS(3845):G12N KRAS(3845):G13D KRAS(3845):G12D

Genes: BRAF(673) NRAS(4893) KRAS(3845)

Variants: V600E G13C Q61H Q61L G12N G13D G12D

[Paper-level Aggregated] PMCID: PMC10011885

Evidence Type(s): Prognostic

Summary: Mutation: V600E | Summary: Higher levels of ctDNA for the BRAF V600E mutation at baseline are associated with inferior progression-free survival (PFS) and overall survival (OS). The mutation correlates with disease outcomes, as patients with higher week 2 and week 4 baseline ratios had inferior PFS and OS, indicating its prognostic significance.

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

Genes: BRAF(673)

Variants: V600E

[Paper-level Aggregated] PMCID: PMC10011885

Evidence Type(s): Diagnostic

Summary: Mutation: V600E | Summary: The presence of the BRAF V600E mutation is used to classify patients with selected cancers, confirming their mutation-positive status. It is also utilized to define and classify patients based on the presence of mutant ctDNA in plasma, indicating its role in diagnosing the disease.

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

Genes: BRAF(673)

Variants: V600E

[Paper-level Aggregated] PMCID: PMC10011885

Evidence Type(s): Predictive

Summary: Mutation: V600E | Summary: The BRAF V600E mutation correlates with clinical benefit and treatment response, as patients with lower ctDNA levels achieved better outcomes. It is associated with early changes in ctDNA levels that predict outcomes to combination vemurafenib and erlotinib therapy. Additionally, it serves as a predictor of progression-free survival (PFS) and overall survival (OS) based on week 2 and week 4 baseline ratios of ctDNA levels. The mutation is also linked to the development of combination therapies involving oral BRAF inhibitors and EGFR-targeting antibodies, and it is associated with treatment response to vemurafenib and erlotinib in metastatic colorectal cancer.

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

Genes: BRAF(673)

Variants: V600E

[Paper-level Aggregated] PMCID: PMC9900321

Evidence Type(s): Oncogenic

Summary: Mutation: Gly-to-Asp | Summary: The Gly-to-Asp mutation (KRASG12D) is prevalent in pancreatic ductal adenocarcinoma and contributes to tumor development and progression, as evidenced by its high occurrence in patients with this cancer type.

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

Genes: KRAS(3845)

Variants: Gly-to-Asp

[Paper-level Aggregated] PMCID: PMC9900321

Evidence Type(s): Predictive

Summary: Mutation: Gly-to-Asp | Summary: The Gly-to-Asp mutation (KRASG12D) is associated with the efficacy of the small-molecule KRASG12D inhibitor, MRTX1133, indicating a correlation with treatment response in pancreatic ductal adenocarcinoma models.

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

Genes: KRAS(3845)

Variants: Gly-to-Asp

[Paper-level Aggregated] PMCID: PMC9859631

Evidence Type(s): Oncogenic

Summary: Mutation: c.1899-880_1946+761del | Summary: The variant c.1899-880_1946+761del was detected in two patients, indicating its potential role in tumor development or progression.

Evidence Type: Oncogenic Mutation: L858R | Summary: The L858R mutation contributes to tumor development in advanced LUAD and is relevant for predicting response to osimertinib therapy.

Evidence Type: Oncogenic Mutation: L755S | Summary: The L755S mutation is suggested as a potential resistance mechanism in the context of osimertinib treatment.

Evidence Type: Oncogenic Mutation: D769Y | Summary: The D769Y mutation is indicated as a possible resistance mechanism following treatment with osimertinib.

Evidence Type: Oncogenic Mutation: c.1899-32_1909del | Summary: The c.1899-32_1909del alteration is detected as a concurrent alteration in the context of resistance mechanisms after osimertinib progression.

Evidence Type: Oncogenic Mutation: D1288N | Summary: The D1288N mutation is associated with MET TKI resistance, indicating its role in tumor development or progression.

Evidence Type: Oncogenic Mutation: L1195I | Summary: The L1195I mutation is known as a secondary mutation associated with MET TKI resistance, contributing to tumor progression.

Evidence Type: Oncogenic Mutation: L1195V | Summary: The L1195V mutation is recognized as a secondary mutation linked to MET TKI resistance, playing a role in tumor development.

Evidence Type: Oncogenic Mutation: Y1230H | Summary: The Y1230H mutation is identified as a secondary mutation associated with MET TKI resistance, indicating its contribution to tumor progression.

Gene→Variant (gene-first): ERBB2(2064):c.1899-880_1946+761del EGFR(1956):L858R ERBB2(2064):L755S ERBB2(2064):D769Y ERBB2(2064):c.1899-32_1909del NA:D1288N NA:L1195I SLTM(79811):L1195V SLTM(79811):Y1230H

Genes: ERBB2(2064) EGFR(1956) NA SLTM(79811)

Variants: c.1899-880_1946+761del L858R L755S D769Y c.1899-32_1909del D1288N L1195I L1195V Y1230H

[Paper-level Aggregated] PMCID: PMC9859631

Evidence Type(s): Predictive

Summary: Mutation: c.1899-2A>G | Summary: The variant c.1899-2A>G was identified in a patient after treatment, suggesting a correlation with treatment response or resistance.

Evidence Type: Predictive Mutation: L858R | Summary: The L858R mutation in EGFR is associated with advanced LUAD and is relevant for predicting response to osimertinib therapy.

Gene→Variant (gene-first): ERBB2(2064):c.1899-2A>G EGFR(1956):L858R

Genes: ERBB2(2064) EGFR(1956)

Variants: c.1899-2A>G L858R

[Paper-level Aggregated] PMCID: PMC9837058

Evidence Type(s): Functional

Summary: Mutation: D915N | Summary: The D915N mutation is described as a kinase dead mutation that does not cause significant changes in protein conformation or membrane binding, indicating its role in altering molecular function without affecting these properties.

Evidence Type: Functional Mutation: N345K | Summary: The N345K mutation in p110alpha is associated with altered membrane binding properties, as evidenced by HDX-MS experiments showing protection in specific regions of the protein when interacting with membranes, indicating a change in molecular function related to membrane association.

Evidence Type: Functional Mutation: E726K | Summary: The E726K mutation alters molecular or biochemical function, particularly in relation to the disengagement of the ABD and p85 from the catalytic core, suggesting conformational changes associated with this mutation.

Evidence Type: Functional Mutation: H1047R | Summary: The H1047R mutation alters molecular function by enhancing membrane binding and increasing basal ATPase activity. It is associated with alterations in molecular or biochemical function, as indicated by the analysis of perturbations in conformation observed in HDX-MS experiments, and shows unique differences in binding interactions upon pY binding.

Evidence Type: Functional Mutation: His1047 | Summary: His1047 is involved in extensive interactions within the kinase domain, indicating that it plays a role in the molecular function of the protein.

Evidence Type: Functional Mutation: Met1043 | Summary: Met1043 is mentioned as a hydrophobic residue that contributes to the structural integrity of the kinase domain, suggesting its role in the molecular function of the protein.

Evidence Type: Functional Mutation: G1049R | Summary: The G1049R mutation alters molecular function by enhancing membrane binding and increasing basal ATPase activity. It shows significantly increased ATPase activity compared to wild type, indicating an alteration in molecular function.

Evidence Type: Functional Mutation: M1043L | Summary: The M1043L mutation alters molecular function by increasing basal ATPase activity with a limited effect on membrane binding. It demonstrates significantly increased ATPase activity compared to wild type and is described in the context of kinase activity.

Evidence Type: Functional Mutation: N1068fs | Summary: The N1068fs mutation alters molecular function by increasing membrane binding without affecting basal ATPase activity and is described in the context of being a kinase dead variant.

Gene→Variant (gene-first): PIK3CA(5290):D915N PIK3CA(5290):N345K PIK3CA(5290):E726K PIK3CA(5290):H1047R PIK3CA(5290):His1047 PIK3CA(5290):Met1043 PIK3CA(5290):G1049R PIK3CA(5290):M1043L PIK3CA(5290):N1068fs

Genes: PIK3CA(5290)

Variants: D915N N345K E726K H1047R His1047 Met1043 G1049R M1043L N1068fs

[Paper-level Aggregated] PMCID: PMC9837058

Evidence Type(s): Oncogenic

Summary: Mutation: N345K | Summary: The N345K mutation is associated with increased membrane binding for oncogenic mutants, suggesting it contributes to tumor development or progression.

Evidence Type: Oncogenic Mutation: G106V | Summary: The G106V mutation is linked to increased membrane binding for oncogenic mutants, indicating its role in tumor development or progression.

Evidence Type: Oncogenic Mutation: G118D | Summary: The G118D mutation is associated with increased membrane binding for oncogenic mutants, suggesting it contributes to tumor development or progression.

Evidence Type: Oncogenic Mutation: E726K | Summary: The mutation E726K is mentioned in the context of oncogenic mutations, indicating its potential contribution to tumor development or progression, as it is part of a comparison with other missense oncogenic mutations.

Evidence Type: Oncogenic Mutation: H1047R | Summary: The H1047R mutation is described as an oncogenic mutation that contributes to tumor development by increasing membrane binding through alterations in the kinase domain structure. It also activates p110alpha, contributing to tumor development or progression by leading to activation through disruption of the inhibitory conformation of the C-terminal tail. H1047R/L is identified as the most frequent oncogenic mutation, contributing to tumor development or progression.

Evidence Type: Oncogenic Mutation: M1043L/I | Summary: M1043L/I is a frequent missense mutation that is associated with oncogenic behavior in tumor samples and is mentioned as activating p110alpha, suggesting its involvement in tumor development or progression.

Evidence Type: Oncogenic Mutation: G1049R | Summary: G1049R is noted as a frequent missense mutation that contributes to tumor development or progression. It activates p110alpha through distinct mechanisms, indicating its role in tumor development or progression, and contributes to tumor development by leading to activation through disruption of the inhibitory conformation of the C-terminal tail.

Evidence Type: Oncogenic Mutation: N1068fs | Summary: N1068fs is an activating frameshift variant that alters the C-terminus and is associated with oncogenic behavior in tumor samples.

Gene→Variant (gene-first): PIK3CA(5290):N345K PIK3CA(5290):G106V PIK3CA(5290):G118D PIK3CA(5290):E726K PIK3CA(5290):H1047R PIK3CA(5290):M1043L/I PIK3CA(5290):G1049R PIK3CA(5290):N1068fs

Genes: PIK3CA(5290)

Variants: N345K G106V G118D E726K H1047R M1043L/I G1049R N1068fs

[Paper-level Aggregated] PMCID: PMC9468105

Evidence Type(s): Oncogenic

Summary: Mutation: c.4110 + 2 T > G | Summary: The c.4110 + 2 T > G splice site mutation contributes to the somatic inactivation of the remaining wild-type NF1 allele, indicating its role in tumor development.

Evidence Type: Oncogenic Mutation: p.V600E | Summary: The BRAF p.V600E mutation is associated with pleomorphic xanthoastrocytoma, indicating its role in tumor development or progression.

Gene→Variant (gene-first): NF1(4763):c.4110 + 2 T > G BRAF(673):p.V600E

Genes: NF1(4763) BRAF(673)

Variants: c.4110 + 2 T > G p.V600E

[Paper-level Aggregated] PMCID: PMC9468105

Evidence Type(s): Predisposing

Summary: Mutation: p.R1276 | Summary: The p.R1276 mutation is described as a germline mutation associated with an autosomal dominant tumor predisposition syndrome, indicating it confers inherited risk for disease.

Evidence Type: Predisposing

Gene→Variant (gene-first): NF1(4763):p.R1276*

Genes: NF1(4763)

Variants: p.R1276*

[Paper-level Aggregated] PMCID: PMC9468105

Evidence Type(s): Prognostic

Summary: Mutation: p.V600E | Summary: Kaplan-Meier survival analysis suggests that patients with NF1-associated gliomas, including those with the p.V600E mutation, have inferior outcomes compared to other groups.

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

Genes: BRAF(673)

Variants: p.V600E

[Paper-level Aggregated] PMCID: PMC9441062

Evidence Type(s): Oncogenic

Summary: Mutation: G719C | Summary: The G719C mutation is part of a double-mutant patient cohort, indicating its contribution to tumor development in the context of acquired RET fusions.

Evidence Type: Oncogenic Mutation: L858R | Summary: The L858R mutation is identified in a significant proportion of patients, suggesting its role in tumor development in NSCLC.

Evidence Type: Oncogenic Mutation: S768I | Summary: The S768I mutation is included in a double-mutant patient cohort, indicating its contribution to tumor development in the context of acquired RET fusions.

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

Genes: EGFR(1956)

Variants: G719C L858R S768I

[Paper-level Aggregated] PMCID: PMC9441062

Evidence Type(s): Prognostic

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

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

Genes: EGFR(1956)

Variants: L858R

[Paper-level Aggregated] PMCID: PMC9441062

Evidence Type(s): Predictive

Summary: Mutation: T790M | Summary: The T790M mutation is associated with resistance to EGFR-TKIs, indicating its role in treatment response.

Evidence Type: Predictive Mutation: C797S/G | Summary: The C797S/G mutation is identified as a resistance mechanism to EGFR-TKIs, suggesting its relevance in therapy response.

Evidence Type: Predictive Mutation: L718V/Q | Summary: The L718V/Q mutation is noted as a potential resistance mechanism to EGFR-TKIs, highlighting its impact on treatment sensitivity.

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

Genes: EGFR(1956)

Variants: T790M C797S/G L718V/Q

[Paper-level Aggregated] PMCID: PMC9402235

Evidence Type(s): Functional

Summary: Mutation: c.236A>G; p.Tyr79Cys | Summary: The c.236A>G (p.Tyr79Cys) variant alters the molecular function of the ELOC gene, as the Tyr79 residue is critical for forming a hydrogen bond with the Pro154 residue within the pVHL alpha domain. It has been shown to mimic the effects of pVHL deficiency on hypoxic signaling and is associated with mosaicism, suggesting it alters molecular or biochemical function.

Evidence Type: Functional Mutation: c.261_272del (p.Thr88_Pro91del) | Summary: The c.261_272del (p.Thr88_Pro91del) variant is described as an in-frame deletion that alters molecular function, contributing to the understanding of ELOC variants in RCC.

Gene→Variant (gene-first): HIF1A(3091):c.236A>G HIF1A(3091):p.Tyr79Cys NA:c.261_272del (p.Thr88_Pro91del)

Genes: HIF1A(3091) NA

Variants: c.236A>G p.Tyr79Cys c.261_272del (p.Thr88_Pro91del)

[Paper-level Aggregated] PMCID: PMC9402235

Evidence Type(s): Oncogenic

Summary: Mutation: c.236A>G; p.Tyr79Cys | Summary: The c.236A>G (p.Tyr79Cys) variant is noted as a mutational hotspot in sporadic VHL-competent renal cell carcinoma (RCC) and is implicated in tumor development due to its location in the tetramerization domain of the ELOC gene, which is essential for its function in the context of VHL disease. It is also described as a somatic variant in RCCs, contributing to tumor development in VHL-independent renal tumorigenesis.

Evidence Type: Oncogenic Mutation: c.274G>A; p.Glu92Lys | Summary: The c.274G>A (p.Glu92Lys) variant is identified as a somatic variant in RCC, contributing to tumor development.

Evidence Type: Oncogenic Mutation: c.74A>T; p.Asp25Val | Summary: The c.74A>T (p.Asp25Val) variant is reported as a somatic variant in RCC, indicating its role in tumor development.

Evidence Type: Oncogenic Mutation: c.311T>A; p.Leu104Gln | Summary: The c.311T>A (p.Leu104Gln) variant is noted as a somatic variant in RCC, suggesting its involvement in tumor progression.

Gene→Variant (gene-first): HIF1A(3091):c.236A>G HIF1A(3091):p.Tyr79Cys RET(5979):c.274G>A VAV1(7409):p.Glu92Lys KRT7(3855):c.74A>T KRT7(3855):p.Asp25Val ELOC(6921):c.311T>A ELOC(6921):p.Leu104Gln

Genes: HIF1A(3091) RET(5979) VAV1(7409) KRT7(3855) ELOC(6921)

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

[Paper-level Aggregated] PMCID: PMC9402235

Evidence Type(s): Predisposing

Summary: Mutation: c.236A>G; p.Tyr79Cys | Summary: The variant is described as a de novo pathogenic variant identified in a proband with VHL disease, indicating it may confer inherited risk for the disease.

Gene→Variant (gene-first): HIF1A(3091):c.236A>G HIF1A(3091):p.Tyr79Cys

Genes: HIF1A(3091)

Variants: c.236A>G p.Tyr79Cys

[Paper-level Aggregated] PMCID: PMC9398166

Evidence Type(s): Functional

Summary: Mutation: I1171N/S/T | Summary: The I1171N/S/T mutations are described in the context of their impact on the potency of TPX-0131, indicating that these mutations alter the molecular function related to drug response.

Gene→Variant (gene-first): NA:I1171N/S/T

Genes: NA

Variants: I1171N/S/T

[Paper-level Aggregated] PMCID: PMC9398166

Evidence Type(s): Oncogenic

Summary: Mutation: G1202 | Summary: The G1202 mutation contributes to tumor development by obstructing binding of ALK inhibitors, which is characteristic of oncogenic behavior in cancer progression.

Evidence Type: Oncogenic Mutation: G1202R | Summary: The G1202R mutation is part of the EML4-ALK oncogenic fusion proteins and is described as a major resistance mechanism to first-generation ALK inhibitors, contributing to tumor development and progression. It is also noted as a solvent front mutation that demonstrates potent inhibition of cell proliferation against cells harboring this mutation.

Evidence Type: Oncogenic Mutation: L1196M | Summary: The L1196M mutation is identified as a gatekeeper mutation and a significant resistance mechanism to first-generation ALK inhibitors, contributing to tumor development. It is included in the EML4-ALK oncogenic fusion context, indicating its role in tumor progression, with TPX-0131 showing significantly greater potency against this mutation compared to previous ALK inhibitors.

Evidence Type: Oncogenic Mutation: L1198F | Summary: The L1198F mutation is characterized as a hinge region mutation and is part of the EML4-ALK oncogenic fusion proteins, suggesting its role in tumor progression. TPX-0131 exhibits high potency against this mutation.

Evidence Type: Oncogenic Mutation: G1269A | Summary: The G1269A mutation is noted as a resistance mutation, with TPX-0131 showing moderate potency against cells harboring this mutation.

Gene→Variant (gene-first): ALK(238):G1202 ALK(238):G1202R ALK(238):L1196M ALK(238):L1198F ALK(238):G1269A

Genes: ALK(238)

Variants: G1202 G1202R L1196M L1198F G1269A

[Paper-level Aggregated] PMCID: PMC9398166

Evidence Type(s): Predictive

Summary: Mutation: G1202 | Summary: The G1202 mutation is associated with resistance to second-generation ALK inhibitors, indicating its relevance in predicting treatment response and resistance to specific therapies.

Evidence Type: Predictive Mutation: C1156Y | Summary: C1156Y is inhibited by TPX-0131 with an IC50 of <1 nmol/L, indicating a correlation with response to this specific therapy.

Evidence Type: Predictive Mutation: E1210K | Summary: E1210K is inhibited by TPX-0131 with an IC50 of <1 nmol/L, suggesting it correlates with response to this specific therapy.

Evidence Type: Predictive Mutation: S1206C | Summary: S1206C is inhibited by TPX-0131 with an IC50 of <1 nmol/L, indicating a correlation with response to this specific therapy.

Evidence Type: Predictive Mutation: L1198F | Summary: The L1198F mutation, in conjunction with G1202R, demonstrates resistance to lorlatinib, highlighting its predictive value for treatment response to TPX-0131. Additionally, the L1198F mutation in the EML4-ALK fusion shows a complete tumor regression in response to TPX-0131 treatment in a CDX model.

Evidence Type: Predictive Mutation: L1196M | Summary: The L1196M mutation, when combined with G1202R, shows a similar resistance pattern to lorlatinib, indicating its role in treatment response to TPX-0131. It is also part of the compound mutation G1202R/L1196M, which shows a correlation with response to TPX-0131 treatment, indicating its predictive value in therapy.

Evidence Type: Predictive Mutation: T1151M | Summary: T1151M is inhibited by TPX-0131 with an IC50 of 1 to 2 nmol/L, suggesting it correlates with response to this specific therapy.

Evidence Type: Predictive Mutation: F1174L | Summary: F1174L is inhibited by TPX-0131 with an IC50 of <1 nmol/L, indicating a correlation with response to this specific therapy.

Evidence Type: Predictive Mutation: F1245C | Summary: F1245C is inhibited by TPX-0131 with an IC50 of <1 nmol/L, suggesting it correlates with response to this specific therapy.

Evidence Type: Predictive Mutation: R1275Q | Summary: R1275Q is inhibited by TPX-0131 with an IC50 of <1 nmol/L, indicating a correlation with response to this specific therapy.

Evidence Type: Predictive Mutation: G1202R | Summary: The G1202R mutation is associated with a response to TPX-0131 treatment, demonstrating dose-dependent tumor growth inhibition (TGI) in a CDX model. It is also associated with resistance to lorlatinib, as indicated by the higher IC50 values, suggesting that it correlates with treatment response to TPX-0131. Additionally, the G1202R mutation in the EML4-ALK fusion is associated with a response to TPX-0131 treatment, as evidenced by the correlation of tumor growth inhibition with TPX-0131 exposure and suppression of ALK phosphorylation.

Evidence Type: Predictive Mutation: G1269A | Summary: The G1269A mutation is linked to the response to TPX-0131, suggesting it may predict sensitivity to this specific therapy.

Evidence Type: Predictive Mutation: L1204V | Summary: The L1204V mutation shows a correlation with the response to TPX-0131, indicating its predictive role in therapy effectiveness.

Gene→Variant (gene-first): ALK(238):G1202 ALK(238):C1156Y ALK(238):E1210K ALK(238):S1206C ALK(238):L1198F ALK(238):L1196M ALK(238):T1151M ALK(238):F1174L ALK(238):F1245C ALK(238):R1275Q ALK(238):G1202R ALK(238):G1269A ALK(238):L1204V

Genes: ALK(238)

Variants: G1202 C1156Y E1210K S1206C L1198F L1196M T1151M F1174L F1245C R1275Q G1202R G1269A L1204V

[Paper-level Aggregated] PMCID: PMC9365372

Evidence Type(s): Oncogenic

Summary: Mutation: T790M | Summary: The T790M mutation is associated with tumor development and progression in non-small cell lung cancer (NSCLC), highlighting its oncogenic role and contributing to the oncogenic characteristics of the cancer.

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

Genes: EGFR(1956)

Variants: T790M

[Paper-level Aggregated] PMCID: PMC9365372

Evidence Type(s): Diagnostic

Summary: Mutation: T790M | Summary: The T790M mutation is used to classify patients as T790M-negative, which is a significant reason for exclusion from treatment in the study.

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

Genes: EGFR(1956)

Variants: T790M

[Paper-level Aggregated] PMCID: PMC9365372

Evidence Type(s): Predictive

Summary: Mutation: T790M | Summary: The T790M mutation is associated with screening failure for treatment and correlates with treatment responses to abivertinib, indicating its predictive value for therapy effectiveness and objective response rate (ORR). It is linked to resistance against prior EGFR inhibitors and is evaluated for its role in determining the efficacy of abivertinib in patients with non-small cell lung cancer (NSCLC). Additionally, the presence of the T790M mutation is associated with a favorable clinical response to abivertinib therapy in NSCLC patients.

Evidence Type: Predictive Mutation: Thr790Met | Summary: The Thr790Met mutation is linked to resistance against previous EGFR inhibitors and is being assessed for its impact on the response to abivertinib in non-small cell lung cancer patients.

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

Genes: EGFR(1956)

Variants: T790M Thr790Met

[Paper-level Aggregated] PMCID: PMC9338780

Evidence Type(s): Oncogenic

Summary: Mutation: V600E | Summary: The BRAF V600E mutation contributes to tumor development and progression in anaplastic thyroid cancer (ATC) and is confirmed in a significant portion of patients with advanced thyroid cancer, indicating its oncogenic potential and role in tumor progression.

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

Genes: BRAF(673)

Variants: V600E

[Paper-level Aggregated] PMCID: PMC9338780

Evidence Type(s): Prognostic

Summary: Mutation: V600E | Summary: The presence of the BRAF V600E mutation correlates with improved long-term survival and disease outcome in patients treated with dabrafenib plus trametinib, as indicated by the median duration of response (DOR).

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

Genes: BRAF(673)

Variants: V600E

[Paper-level Aggregated] PMCID: PMC9338780

Evidence Type(s): Diagnostic

Summary: Mutation: V600E | Summary: The presence of the BRAF V600E mutation is used to define and classify anaplastic thyroid cancer and confirm the diagnosis of advanced thyroid cancer, supporting its role as a diagnostic marker for this disease subtype.

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

Genes: BRAF(673)

Variants: V600E

[Paper-level Aggregated] PMCID: PMC9338780

Evidence Type(s): Predictive

Summary: Mutation: V600E | Summary: The BRAF V600E mutation is associated with response to combined therapy with dabrafenib and trametinib in anaplastic thyroid cancer, indicating its predictive value for treatment efficacy. It is evaluated in the context of a study assessing the response to this combination, showing substantial clinical benefit and a high overall response rate (ORR) in patients with this mutation.

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

Genes: BRAF(673)

Variants: V600E

[Paper-level Aggregated] PMCID: PMC8887939

Evidence Type(s): Predictive

Summary: Mutation: A775dupYVMA | Summary: The HER2 A775dupYVMA mutation is associated with an overall response rate (ORR) of 20.0%, indicating its potential predictive value for therapy response.

Evidence Type: Predictive Mutation: G776delinsVC | Summary: The G776delinsVC mutation shows an ORR of 27.3%, suggesting it may also have predictive implications for treatment response.

Gene→Variant (gene-first): ERBB2(2064):A775dupYVMA ERBB2(2064):G776delinsVC

Genes: ERBB2(2064)

Variants: A775dupYVMA G776delinsVC

[Paper-level Aggregated] PMCID: PMC8881279

Evidence Type(s): Functional

Summary: Mutation: E401G | Summary: The ERBB2 E401G variant alters molecular function by enhancing C-terminal phosphorylation, stabilizing the dimer interface of the HER2-EGFR complex, and activating the MAPK pathway, contributing to changes in proliferative and invasive capacities of cancer cells. It is associated with increased phosphorylation of HER2 and ERK, and does not contribute to the formation of disulfide-linked dimers.

Evidence Type: Functional Mutation: S310F | Summary: The ERBB2 S310F variant alters molecular function by enhancing C-terminal phosphorylation, stabilizing the dimer interface of the HER2-EGFR complex, and activating the MAPK pathway, leading to a significantly higher proliferation rate in cancer cells. It does not show increases in HER2 dimers.

Evidence Type: Functional Mutation: E321G | Summary: The ERBB2 E321G variant alters molecular function by forming disulfide-linked dimers and is involved in activation mechanisms related to dimer formation and C-terminal phosphorylation.

Evidence Type: Functional Mutation: D845A | Summary: The ERBB2 D845A variant is described as a kinase domain inactivating variant and is part of the evaluation of functional properties related to activation mechanisms.

Gene→Variant (gene-first): FANCC(2176):E401G ERBB2(2064):S310F TP53(7157):E321G ERBB2(2064):D845A

Genes: FANCC(2176) ERBB2(2064) TP53(7157)

Variants: E401G S310F E321G D845A

[Paper-level Aggregated] PMCID: PMC8881279

Evidence Type(s): Oncogenic

Summary: Mutation: E401G | Summary: The ERBB2 E401G variant is identified as a somatic mutation that contributes to tumor development, associated with high allele fraction and ERBB2 gene amplification. It is linked to increased phosphorylation levels of HER2 and EGFR, and is described as an activating mutation, indicating its role in tumor growth and progression.

Evidence Type: Oncogenic Mutation: S310F | Summary: The HER2 S310F mutation is associated with increased phosphorylation levels of HER2 and EGFR, and is classified as an activating mutation, suggesting its contribution to tumor development or progression.

Evidence Type: Oncogenic Mutation: E321G | Summary: The E321G variant is classified as an activating mutation, suggesting its contribution to tumor development or progression.

Gene→Variant (gene-first): FANCC(2176):E401G ERBB2(2064):S310F TP53(7157):E321G

Genes: FANCC(2176) ERBB2(2064) TP53(7157)

Variants: E401G S310F E321G

[Paper-level Aggregated] PMCID: PMC8881279

Evidence Type(s): Diagnostic

Summary: Mutation: E401G | Summary: The ERBB2 E401G variant is detected in a patient with cancer of unknown primary (CUP), suggesting its role in defining or classifying the disease.

Gene→Variant (gene-first): FANCC(2176):E401G

Genes: FANCC(2176)

Variants: E401G

[Paper-level Aggregated] PMCID: PMC8727519

Evidence Type(s): Oncogenic

Summary: Mutation: L858R | Summary: The L858R mutation in EGFR is associated with lung adenocarcinoma and contributes to tumor development.

Evidence Type: Oncogenic Mutation: T790M | Summary: The T790M mutation contributes to tumor development and progression in the context of EGFR-mutated non-small cell lung cancer (NSCLC) and is identified as a potential resistance mechanism to icotinib treatment.

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

Genes: EGFR(1956)

Variants: L858R T790M

[Paper-level Aggregated] PMCID: PMC8727519

Evidence Type(s): Predictive

Summary: Mutation: T790M | Summary: The T790M mutation is associated with resistance to first-generation EGFR tyrosine kinase inhibitors, suggesting its role in predicting treatment response in NSCLC patients.

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

Genes: EGFR(1956)

Variants: T790M

[Paper-level Aggregated] PMCID: PMC8700411

Evidence Type(s): Functional

Summary: Mutation: G770 | Summary: The G770 mutation alters molecular or biochemical function as it is associated with changes in the EGFR protein due to the insertion mutations. The preclinical characterization of an EGFR Exon 20 Insertion Mutant with a G770 equivalence indicates that this variant alters molecular or biochemical function.

Evidence Type: Functional Mutation: V769dupASV | Summary: The V769dupASV mutation affects the biochemical function of EGFR, as evidenced by the differential inhibition of phosphorylated EGFR in response to dacomitinib. Additionally, this mutation shows sensitivity to mobocertinib and poziotinib, suggesting functional alterations in response to these therapies.

Evidence Type: Functional Mutation: Y764insFQEA | Summary: The Y764insFQEA mutation is described as pan-sensitive to all EGFR TKIs tested, indicating a functional alteration in response to these therapies.

Gene→Variant (gene-first): EGFR(1956):G770 EGFR(1956):V769dupASV EGFR(1956):Y764insFQEA

Genes: EGFR(1956)

Variants: G770 V769dupASV Y764insFQEA

[Paper-level Aggregated] PMCID: PMC8700411

Evidence Type(s): Oncogenic

Summary: Mutation: G770 | Summary: The G770 mutation is part of the EGFR exon 20 insertion mutations, which are known to contribute to tumor development or progression in advanced lung cancers. It is implicated in tumor development and is associated with a lack of response to certain EGFR TKIs, supporting its classification as oncogenic.

Evidence Type: Oncogenic Mutation: V769dupASV | Summary: The V769dupASV mutation is implicated in driving proliferation in Ba/F3 cells, suggesting its role in tumor development or progression.

Gene→Variant (gene-first): EGFR(1956):G770 EGFR(1956):V769dupASV

Genes: EGFR(1956)

Variants: G770 V769dupASV

[Paper-level Aggregated] PMCID: PMC8700411

Evidence Type(s): Diagnostic

Summary: Mutation: G770 | Summary: The G770 mutation is associated with advanced lung cancers and is used to classify or define a specific subtype of lung cancer related to EGFR Exon 20 insertion mutations.

Gene→Variant (gene-first): EGFR(1956):G770

Genes: EGFR(1956)

Variants: G770

[Paper-level Aggregated] PMCID: PMC8700411

Evidence Type(s): Predictive

Summary: Mutation: D770_N771insSVD | Summary: The D770_N771insSVD mutation is associated with sensitivity to mobocertinib and poziotinib, indicating its predictive value for response to these therapies.

Evidence Type: Predictive Mutation: V769dupASV | Summary: The V769dupASV mutation shows sensitivity to mobocertinib and poziotinib, but is also associated with a higher IC50 for afatinib and dacomitinib, indicating a correlation with resistance to these therapies. Additionally, it shows altered sensitivity to dacomitinib, suggesting implications for treatment response.

Evidence Type: Predictive Mutation: G770 | Summary: The G770 mutation is associated with sensitivity to EGFR TKIs such as dacomitinib, afatinib, and mobocertinib, as well as with a lack of response to certain EGFR TKIs. It is also correlated with radiographic responses to therapies like poziotinib and mobocertinib, indicating its predictive value for treatment outcomes in patients with advanced lung cancers.

Evidence Type: Predictive Mutation: D770 | Summary: The EGFR-D770 mutation is associated with sensitivity to specific 2nd generation EGFR-TKIs, such as afatinib and dacomitinib, indicating its predictive value for therapy response.

Evidence Type: Predictive Mutation: Y764insFQEA | Summary: The EGFR-Y764insFQEA insertion mutation is responsive to approved EGFR TKIs, highlighting its predictive significance for treatment outcomes.

Gene→Variant (gene-first): EGFR(1956):D770_N771insSVD EGFR(1956):V769dupASV EGFR(1956):G770 EGFR(1956):D770 EGFR(1956):Y764insFQEA

Genes: EGFR(1956)

Variants: D770_N771insSVD V769dupASV G770 D770 Y764insFQEA

[Paper-level Aggregated] PMCID: PMC8688876

Evidence Type(s): Functional

Summary: Mutation: G12 | Summary: The G12 mutation is associated with alterations in the biochemical properties of the GTPase encoded by KRAS, affecting functions such as GTP binding, nucleotide exchange, and distinct vulnerabilities to the enzyme. It is also linked to changes in molecular function, particularly in relation to GAP-mediated hydrolysis and GTP-binding domain activity.

Evidence Type: Functional Mutation: G13 | Summary: The G13 mutation exhibits higher induction with higher variance and is linked to changes in biochemical properties that affect RAF affinity and may influence downstream signaling mechanisms. It is also associated with alterations in molecular function.

Evidence Type: Functional Mutation: Q61 | Summary: The Q61 mutation affects the biochemical properties of the KRAS GTPase, impacting functions such as GTP binding and nucleotide exchange. It is part of the broader distribution of KRAS hotspot variants and is implicated in functional differences related to GTP hydrolysis and signaling pathways.

Evidence Type: Functional Mutation: G12V | Summary: The G12V mutation is specifically noted for having all six biochemical measurements, indicating its significant impact on the functional properties of the KRAS GTPase. Its RAF affinity profile indicates a change in molecular function.

Evidence Type: Functional Mutation: A146T | Summary: The A146T variant is associated with increased GTP binding and is suggested to alter molecular function by modulating GAP binding and changing the probability of locally unfolded conformations, impacting GAP-mediated hydrolysis rates.

Evidence Type: Functional Mutation: A146V | Summary: The A146V mutation is associated with alterations in local stability and may modulate local unfolding, indicating a change in molecular function. It is also predicted to have an intermediate decrease in RAF affinity.

Evidence Type: Functional Mutation: A59T | Summary: The A59T variant has a distinct profile among the mutants, indicating a potential alteration in molecular function. It is predicted to have an intermediate decrease in RAF affinity.

Evidence Type: Functional Mutation: G12A/R | Summary: The G12A/R variant is part of a cluster that shows similarities with other variants, suggesting functional implications and is associated with comparable effects to G12S, implicating it in altering molecular function related to GAP-mediated hydrolysis.

Evidence Type: Functional Mutation: G12D | Summary: The G12D mutation has been shown to have a specific level of downstream activity, indicating an alteration in molecular or biochemical function. It is discussed in the context of conflicting reports regarding its effects, suggesting it may alter molecular function.

Evidence Type: Functional Mutation: G12S | Summary: The G12S variant is indicated to have comparable effects to G12A/R and is involved in altering molecular function related to GAP-mediated hydrolysis. It is predicted to have a decreased RAF affinity.

Evidence Type: Functional Mutation: G13C | Summary: The G13C variant is part of a group of variants that relate to local stability and may affect local unfolding, suggesting a functional impact. It is also predicted to have RAF affinity comparable to wild-type, indicating no significant alteration in molecular function.

Evidence Type: Functional Mutation: G13V | Summary: The G13V mutation is included in a cluster of variants that influence local stability and local unfolding probabilities, indicating a functional alteration. It is also indicated to have a significant effect on GAP-mediated hydrolysis and is predicted to have an intermediate decrease in RAF affinity.

Evidence Type: Functional Mutation: K117N | Summary: The K117N mutation is identified as a non-hotspot variant that may affect local stability and local unfolding, suggesting a change in molecular function. It is noted to have comparable effects to G13D and Q61H, indicating a potential alteration in molecular function.

Evidence Type: Functional Mutation: T74 | Summary: The T74 mutation is associated with alterations in the biochemical properties of the KRAS GTPase, influencing functions like GTP binding and nucleotide exchange. The T74P variant alters RAF affinity, indicating a change in molecular function related to tumor development.

Evidence Type: Functional Mutation: R164Q | Summary: The R164Q variant behaves like wild-type KRAS, indicating a potential alteration in molecular function. Its RAF affinity profile suggests it alters molecular function in a manner similar to other variants.

Evidence Type: Functional Mutation: Q22K | Summary: The Q22K variant is associated with increased GTP binding and shows a similar RAF affinity profile to other variants, suggesting an alteration in molecular function.

Evidence Type: Functional Mutation: L19F | Summary: The L19F variant shows similarities with hotspot variants, suggesting functional relevance. It is compared to G13D and Q61H, indicating a potential alteration in molecular function and is predicted to have RAF affinity comparable to wild-type.

Evidence Type: Functional Mutation: Q61H | Summary: The Q61H variant is associated with increased GTP binding and is mentioned in relation to its effects on GAP-mediated hydrolysis, suggesting it may alter molecular function. It shows relatively smaller changes in RAF affinity, suggesting a minor alteration in molecular function.

Evidence Type: Functional Mutation: Q61L/P | Summary: The Q61L/P variant is included in a cluster that suggests functional implications.

Evidence Type: Functional Mutation: Q61R | Summary: The Q61R variant shows a distinct RAF affinity profile, indicating a change in molecular function and is predicted to have RAF affinity comparable to wild-type, indicating no significant alteration in molecular function.

Gene→Variant (gene-first): KRAS(3845):G12 KRAS(3845):G13 KRAS(3845):Q61 KRAS(3845):G12V KRAS(3845):A146T HRAS(3265):A146V HRAS(3265):A59T KRAS(3845):G12A/R KRAS(3845):G12D KRAS(3845):G12S KRAS(3845):G13C HRAS(3265):G13V KRAS(3845):K117N ZHX2(22882):T74 KRAS(3845):R164Q KRAS(3845):Q22K KRAS(3845):L19F KRAS(3845):Q61H KRAS(3845):Q61L/P NRAS(4893):Q61R

Genes: KRAS(3845) HRAS(3265) ZHX2(22882) NRAS(4893)

Variants: G12 G13 Q61 G12V A146T A146V A59T G12A/R G12D G12S G13C G13V K117N T74 R164Q Q22K L19F Q61H Q61L/P Q61R

[Paper-level Aggregated] PMCID: PMC8453302

Evidence Type(s): Oncogenic

Summary: Mutation: G292R | Summary: The G292R mutation in HER2 is implicated in tumor development or progression in cervical cancer, supporting its classification as an oncogenic variant.

Gene→Variant (gene-first): ERBB2(2064):G292R

Genes: ERBB2(2064)

Variants: G292R

[Paper-level Aggregated] PMCID: PMC8453302

Evidence Type(s): Predictive

Summary: Mutation: G292R | Summary: The G292R mutation in HER2 is associated with a positive response to pyrotinib in a metastatic cervical adenocarcinoma patient, indicating its predictive value for treatment efficacy.

Evidence Type: Predictive

Gene→Variant (gene-first): ERBB2(2064):G292R

Genes: ERBB2(2064)

Variants: G292R

[Paper-level Aggregated] PMCID: PMC8307492

Evidence Type(s): Oncogenic

Summary: Mutation: L858R | Summary: The L858R mutation is identified as a classical, actionable EGFR mutation that contributes to tumor development or progression in a significant proportion of patients. It is associated with worse outcomes compared to other variants in the context of overall survival analysis and is used to classify and confirm the presence of a specific EGFR mutation in patients.

Evidence Type: Oncogenic Mutation: T790M | Summary: The T790M mutation contributes to tumor development or progression as it is a mechanism of resistance that arises in patients treated with EGFR inhibitors, specifically indicating resistance to the third-generation EGFR inhibitor osimertinib.

Evidence Type: Oncogenic Mutation: G719S | Summary: The G719S mutation is part of a composite mutation that is implicated in tumor development or progression.

Evidence Type: Oncogenic Mutation: L861X | Summary: The L861X mutation is noted as an uncommon but actionable EGFR mutation that may also contribute to tumor development or progression, particularly in patients tested with multi-gene assays.

Evidence Type: Oncogenic Mutation: L861Q | Summary: The L861Q mutation is part of a composite mutation that is implicated in tumor development or progression.

Gene→Variant (gene-first): EGFR(1956):L858R EGFR(1956):T790M EGFR(1956):G719S EGFR(1956):L861X EGFR(1956):L861Q

Genes: EGFR(1956)

Variants: L858R T790M G719S L861X L861Q

[Paper-level Aggregated] PMCID: PMC8307492

Evidence Type(s): Prognostic

Summary: Mutation: L858R | Summary: The L858R mutation correlates with overall survival outcomes in non-small-cell lung cancer (NSCLC) patients, independent of therapy. It is associated with a median overall survival (OS) of 16.7 months and 18.3 months for patients treated with first-line targeted therapy. Patients with this mutation have a comparable prognosis to those with uncommon actionable variants when adjusted for age, sex, and year of diagnosis, indicating its relevance in disease prognosis.

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

Genes: EGFR(1956)

Variants: L858R

[Paper-level Aggregated] PMCID: PMC8307492

Evidence Type(s): Diagnostic

Summary: Mutation: L858R | Summary: The L858R mutation is used to classify and confirm the presence of a specific EGFR mutation in patients, aiding in the diagnosis of the disease.

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

Genes: EGFR(1956)

Variants: L858R

[Paper-level Aggregated] PMCID: PMC8307492

Evidence Type(s): Predictive

Summary: Mutation: L858R | Summary: The L858R mutation is associated with response to first-line EGFR inhibitors and targeted therapy, with survival outcomes indicating it may not perform as well as exon 19 deletions in terms of overall survival (OS).

Evidence Type: Predictive Mutation: T790M | Summary: The T790M mutation is associated with resistance to EGFR inhibitors, specifically indicating a mechanism of resistance to the third-generation EGFR inhibitor osimertinib.

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

Genes: EGFR(1956)

Variants: L858R T790M

[Paper-level Aggregated] PMCID: PMC8285406

Evidence Type(s): Oncogenic

Summary: Mutation: K656E | Summary: The K656E mutation in the FGFR1 tyrosine kinase domain is reported as an oncogenic mutation frequently discovered in glioma.

Evidence Type: Oncogenic Mutation: N546K | Summary: The N546K mutation in the FGFR1 tyrosine kinase domain is identified as an oncogenic mutation commonly found in glioma.

Evidence Type: Oncogenic Mutation: S252W | Summary: The S252W mutation in FGFR2, located in the ligand-binding region, is recognized as an oncogenic hotspot mutation in endometrial cancers.

Evidence Type: Oncogenic Mutation: S249C | Summary: The S249C mutation in FGFR3 is associated with transforming activities in cancer cells, indicating its role in tumor development. It is noted as an oncogenic hotspot mutation in bladder cancer and is identified as the most frequent mutation of FGFR3.

Evidence Type: Oncogenic Mutation: V550L | Summary: The V550L mutation in FGFR4, located in the tyrosine kinase domain, is reported as an oncogenic mutation in rhabdomyosarcoma.

Evidence Type: Oncogenic Mutation: N549H | Summary: The N549H variant in FGFR2 exhibits significant transforming activity, indicating its role in tumor development.

Evidence Type: Oncogenic Mutation: K659E | Summary: The K659E variant in FGFR2 shows significant transforming activity, contributing to tumor progression.

Evidence Type: Oncogenic Mutation: W290C | Summary: The W290C variant in FGFR2 demonstrates significant oncogenic potential compared to wild-type FGFR2.

Evidence Type: Oncogenic Mutation: S342F | Summary: The S342F variant in FGFR4 exhibits significant oncogenicity, indicating its contribution to tumor development.

Evidence Type: Oncogenic Mutation: R248C | Summary: The R248C variant in FGFR3 is located in the ligand binding site and is associated with oncogenic mutations.

Evidence Type: Oncogenic Mutation: G370C | Summary: The G370C variant in FGFR3 is located in the transmembrane domain and is associated with oncogenic mutations.

Evidence Type: Oncogenic Mutation: S371C | Summary: The S371C variant in FGFR3 is located in the transmembrane domain and contributes to oncogenic behavior.

Evidence Type: Oncogenic Mutation: Y373C | Summary: The Y373C variant in FGFR3 is located in the transmembrane domain and is associated with oncogenic mutations.

Evidence Type: Oncogenic Mutation: G380E/R | Summary: The G380E/R variant in FGFR3 is located in the transmembrane domain and contributes to oncogenic behavior.

Evidence Type: Oncogenic Mutation: K650E/M | Summary: The K650E/M variant in FGFR3 is located in the kinase domain and is associated with oncogenic mutations.

Evidence Type: Oncogenic Mutation: K650E | Summary: The K650E mutation, when combined with S249C, shows stronger transforming activities than each single mutation, suggesting its contribution to tumor progression.

Evidence Type: Oncogenic Mutation: K650M | Summary: The K650M mutation, in combination with S249C, exhibits enhanced transforming activities, supporting its role in oncogenesis.

Evidence Type: Oncogenic Mutation: E542K | Summary: The mutation E542K is described as an oncogenic mutation that contributes to tumor development or progression when co-mutated with PIK3CA.

Evidence Type: Oncogenic Mutation: E545K | Summary: The mutation E545K is identified as an oncogenic mutation that plays a role in tumor development or progression in conjunction with PIK3CA.

Evidence Type: Oncogenic Mutation: H1047R | Summary: The mutation H1047R is classified as an oncogenic mutation, indicating its contribution to tumor development or progression when occurring alongside PIK3CA.

Gene→Variant (gene-first): FGFR1(2260):K656E FGFR1(2260):N546K FGFR2(2263):S252W FGFR3(2261):S249C FGFR2(2263):V550L FGFR2(2263):N549H FGFR2(2263):K659E FGFR2(2263):W290C TACC1(6867):S342F FGFR3(2261):R248C FGFR3(2261):G370C FGFR3(2261):S371C FGFR3(2261):Y373C FGFR3(2261):G380E/R FGFR3(2261):K650E/M FGFR3(2261):K650E FGFR3(2261):K650M PIK3CA(5290):E542K PIK3CA(5290):E545K PIK3CA(5290):H1047R

Genes: FGFR1(2260) FGFR2(2263) FGFR3(2261) TACC1(6867) PIK3CA(5290)

Variants: K656E N546K S252W S249C V550L N549H K659E W290C S342F R248C G370C S371C Y373C G380E/R K650E/M K650E K650M E542K E545K H1047R

[Paper-level Aggregated] PMCID: PMC8285406

Evidence Type(s): Predictive

Summary: Mutation: N546K | Summary: The N546K variant is associated with resistance to FGFR TKIs and is included in a cluster that is relatively resistant to all FGFR inhibitors, suggesting its predictive significance in treatment response.

Evidence Type: Predictive Mutation: N549D/K | Summary: The N549D/K variants show relative resistance to FGFR TKIs and are part of a cluster that demonstrates resistance to all FGFR inhibitors, highlighting their predictive value in therapy response.

Evidence Type: Predictive Mutation: N535K | Summary: The N535K variant is sensitive to the FGFR4 inhibitor H3B-6527, indicating its predictive role in therapy response.

Evidence Type: Predictive Mutation: N549D | Summary: The N549D variant in FGFR2 is associated with different drug sensitivities to FGFR inhibitors, indicating a correlation with treatment response.

Evidence Type: Predictive Mutation: N549H | Summary: The N549H variant in FGFR2 shows varying drug sensitivities to FGFR inhibitors, suggesting its role in influencing treatment response.

Evidence Type: Predictive Mutation: K656E | Summary: The K656E variant in FGFR3 is linked to different sensitivities to FGFR inhibitors, indicating its potential impact on treatment response.

Evidence Type: Predictive Mutation: K656M | Summary: The K656M variant in FGFR3 demonstrates varying drug sensitivities to FGFR inhibitors, suggesting its relevance in treatment response.

Evidence Type: Predictive Mutation: K656N | Summary: The K656N variant in FGFR3 is associated with different drug sensitivities to FGFR inhibitors, indicating its role in influencing treatment response.

Evidence Type: Predictive Mutation: G12V | Summary: The KRAS G12V variant is associated with resistance to all FGFR inhibitors, indicating its predictive role in therapy response.

Evidence Type: Predictive Mutation: K650M | Summary: The K650M mutation in FGFR3 shows a correlation with response to the FGFR TKI E7090, and the drug responses of tumors with this variant were similar to those recorded in vitro, suggesting a correlation with therapy effectiveness.

Evidence Type: Predictive Mutation: K650N | Summary: The K650N mutation in FGFR3 demonstrates decreased phosphorylation at lower concentrations of the FGFR TKI E7090 and was associated with significantly decreased tumor volumes in response to both E7090 and erdafitinib, indicating a favorable response to these therapies.

Evidence Type: Predictive Mutation: N549K | Summary: Tumors with the FGFR2 N549K variant exhibited a better response to treatment with E7090 compared to erdafitinib, suggesting a correlation with therapy effectiveness.

Evidence Type: Predictive Mutation: R248C | Summary: The FGFR3 R248C variant showed significant antitumor activity against tumors treated with E7090, indicating a potential sensitivity to this therapy.

Evidence Type: Predictive Mutation: Y373C | Summary: The Y373C mutation, when combined with S249C, does not significantly affect sensitivity to E7090 and erdafitinib, indicating its potential role in treatment response dynamics.

Evidence Type: Predictive Mutation: S249C | Summary: The S249C mutation in FGFR3 is associated with a partial or complete response to treatment with FGFR TKIs, indicating its correlation with drug efficacy.

Gene→Variant (gene-first): FGFR1(2260):N546K FGFR2(2263):N549D/K FGFR4(2264):N535K NA:N549D FGFR2(2263):N549H FGFR1(2260):K656E NA:K656M NA:K656N KRAS(3845):G12V FGFR3(2261):K650M FGFR3(2261):K650N FGFR2(2263):N549K FGFR3(2261):R248C FGFR3(2261):Y373C FGFR3(2261):S249C

Genes: FGFR1(2260) FGFR2(2263) FGFR4(2264) NA KRAS(3845) FGFR3(2261)

Variants: N546K N549D/K N535K N549D N549H K656E K656M K656N G12V K650M K650N N549K R248C Y373C S249C

[Paper-level Aggregated] PMCID: PMC8255005

Evidence Type(s): Oncogenic

Summary: Mutation: D835Y | Summary: The D835Y mutation is part of the FLT3-TKD mutations that contribute to tumor development and progression in acute myeloid leukemia (AML).

Evidence Type: Oncogenic Mutation: F691 | Summary: The F691 mutation is implicated in the resistance to FLT3 inhibitors and contributes to tumor progression in acute myeloid leukemia (AML).

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

Genes: FLT3(2322)

Variants: D835Y F691

[Paper-level Aggregated] PMCID: PMC8255005

Evidence Type(s): Prognostic

Summary: Mutation: D835 | Summary: The D835 mutation is associated with poor prognosis in acute myeloid leukemia (AML).

Evidence Type: Prognostic Mutation: D835Y | Summary: The D835Y mutation is associated with poor prognosis in acute myeloid leukemia (AML).

Evidence Type: Prognostic

Gene→Variant (gene-first): FLT3(2322):D835 FLT3(2322):D835Y

Genes: FLT3(2322)

Variants: D835 D835Y

[Paper-level Aggregated] PMCID: PMC8255005

Evidence Type(s): Predictive

Summary: Mutation: F691L | Summary: The F691L mutation is described as a "gatekeeper" mutation that is resistant to most available FLT3 inhibitors, indicating its role in treatment resistance.

Evidence Type: Predictive Mutation: F691 | Summary: The F691 mutation is implicated in the resistance to FLT3 inhibitors and contributes to tumor progression in AML.

Gene→Variant (gene-first): FLT3(2322):F691L FLT3(2322):F691

Genes: FLT3(2322)

Variants: F691L F691

[Paper-level Aggregated] PMCID: PMC8203843

Evidence Type(s): Oncogenic

Summary: Mutation: R132H | Summary: The R132H variant contributes to tumor development and progression, particularly in the context of glioma, as it is implicated in cancer-related pathways.

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

Genes: IDH1(3417)

Variants: R132H

[Paper-level Aggregated] PMCID: PMC8203843

Evidence Type(s): Predictive

Summary: Mutation: R132H | Summary: The R132H variant is associated with sensitivity to PARP inhibitors, indicating a correlation with treatment response.

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

Genes: IDH1(3417)

Variants: R132H

[Paper-level Aggregated] PMCID: PMC8078423

Evidence Type(s): Oncogenic

Summary: Mutation: V600E | Summary: The BRAF V600E mutation is implicated in tumor development and progression in colorectal cancer and contributes to tumor development and progression in metastatic colorectal cancer.

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

Genes: BRAF(673)

Variants: V600E

[Paper-level Aggregated] PMCID: PMC8078423

Evidence Type(s): Prognostic

Summary: Mutation: BRAFV600E | Summary: The presence of the BRAFV600E mutation correlates with improved overall survival and objective response rate in patients with metastatic colorectal cancer undergoing treatment.

Evidence Type: Prognostic Mutation: V600E | Summary: The presence of the BRAF V600E mutation correlates with overall survival (OS) outcomes in patients with metastatic colorectal cancer, independent of the therapy received.

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

Genes: BRAF(673)

Variants: BRAFV600E V600E

[Paper-level Aggregated] PMCID: PMC8078423

Evidence Type(s): Predictive

Summary: Mutation: BRAFV600E | Summary: The BRAFV600E mutation is associated with response to targeted therapies such as encorafenib and cetuximab in patients with metastatic colorectal cancer.

Evidence Type: Predictive Mutation: V600E | Summary: The BRAF V600E mutation is associated with treatment response in patients with metastatic colorectal cancer (mCRC), including improved overall survival, objective response rate, and progression-free survival when treated with encorafenib plus cetuximab.

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

Genes: BRAF(673)

Variants: BRAFV600E V600E

[Paper-level Aggregated] PMCID: PMC8077124

Evidence Type(s): Oncogenic

Summary: Mutation: p.K656E | Summary: The p.K656E mutation in FGFR1 is described as a known hotspot mutation that is both activating and transforming, indicating its role in tumor development and progression.

Evidence Type: Oncogenic Mutation: p.R132H | Summary: The IDH1 p.R132H mutation is associated with tumor development or progression in gliomas, although this specific tumor was noted to be IDH1 negative.

Evidence Type: Oncogenic Mutation: p.V561M | Summary: The p.V561M mutation in FGFR1 is identified as an activating somatic mutation that contributes to tumor development.

Gene→Variant (gene-first): FGFR1(2260):p.K656E IDH1(3417):p.R132H FGFR1(2260):p.V561M

Genes: FGFR1(2260) IDH1(3417)

Variants: p.K656E p.R132H p.V561M

[Paper-level Aggregated] PMCID: PMC8077124

Evidence Type(s): Predictive

Summary: Mutation: p.V561M | Summary: The p.V561M mutation is characterized as a gatekeeper mutation that imparts resistance to FGFR inhibitors and is associated with the potential response to FGFR inhibitors, indicating its importance in therapeutic strategies for the patient's pilomyxoid astrocytoma.

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

Gene→Variant (gene-first): FGFR1(2260):p.V561M FGFR1(2260):p.K656E

Genes: FGFR1(2260)

Variants: p.V561M p.K656E

[Paper-level Aggregated] PMCID: PMC8040738

Evidence Type(s): Functional

Summary: Mutation: p.T599dup | Summary: The BRAF p.T599dup mutation is likely to alter molecular or biochemical function, as it is associated with a specific tumor type and was detected through deep, targeted sequencing of tumor DNA.

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

Genes: BRAF(673)

Variants: p.T599dup

[Paper-level Aggregated] PMCID: PMC8040738

Evidence Type(s): Oncogenic

Summary: Mutation: p.T599dup | Summary: The BRAF p.T599dup mutation contributes to tumor development or progression, as evidenced by its identification in a low-grade glioma and the patient's diagnosis of a ganglioglioma, indicating the need for targeted therapy due to tumor growth. Its presence in tumor-extracted DNA from the patient's resection further supports its role in tumor development.

Evidence Type: Oncogenic Mutation: p.V600E | Summary: The BRAF p.V600E mutation is known to be oncogenic, as it is indicated for tumors that respond to targeted therapies, highlighting its role in tumor development.

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

Genes: BRAF(673)

Variants: p.T599dup p.V600E

[Paper-level Aggregated] PMCID: PMC8040738

Evidence Type(s): Predictive

Summary: Mutation: p.T599dup | Summary: The BRAF p.T599dup mutation is associated with the patient's response to combination targeted therapy with a selective BRAF inhibitor (dabrafenib) and MEK inhibitor (trametinib), indicating its predictive value for treatment efficacy.

Evidence Type: Predictive Mutation: p.V600E | Summary: Although the patient does not have a BRAF p.V600E mutation, the report discusses the efficacy of BRAF and MEK inhibitors in tumors harboring BRAF alterations, suggesting predictive implications for treatment strategies.

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

Genes: BRAF(673)

Variants: p.T599dup p.V600E

[Paper-level Aggregated] PMCID: PMC8033310

Evidence Type(s): Functional

Summary: Mutation: E545K | Summary: The PIK3CA E545K mutation alters cell viability and apoptosis in TNBC cell lines, indicating a change in molecular function related to cell proliferation and survival. It also downregulates Caspase 3 and upregulates Xiap in tumor tissues, affecting apoptosis.

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

Genes: PIK3CA(5290)

Variants: E545K

[Paper-level Aggregated] PMCID: PMC8033310

Evidence Type(s): Oncogenic

Summary: Mutation: E545K | Summary: The E545K mutation in the PIK3CA gene is associated with tumor development and progression in TNBC cell lines, contributing to increased tumor volume, enhanced aggressiveness, and a migratory phenotype. It promotes growth and inhibits apoptosis, indicating its significant role in tumorigenesis.

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

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

Genes: PIK3CA(5290)

Variants: E545K H1047R

[Paper-level Aggregated] PMCID: PMC8033310

Evidence Type(s): Diagnostic

Summary: Mutation: E545K | Summary: The E545K mutation is associated with the diagnosis of invasive cancer in patients with PIK3CA mutations, as indicated by its presence in the cohort studied.

Evidence Type: Diagnostic Mutation: H1047R | Summary: The H1047R mutation is also linked to the diagnosis of invasive cancer in patients with PIK3CA mutations, as observed in the cohort analyzed.

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

Genes: PIK3CA(5290)

Variants: E545K H1047R

[Paper-level Aggregated] PMCID: PMC8033310

Evidence Type(s): Predictive

Summary: Mutation: E545K | Summary: The presence of the PIK3CA E545K mutation correlates with decreased sensitivity to chemotherapy and is associated with induced resistance to chemotherapy in TNBC cells, suggesting it may influence treatment response in TNBC patients.

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

Genes: PIK3CA(5290)

Variants: E545K

[Paper-level Aggregated] PMCID: PMC8008494

Evidence Type(s): Functional

Summary: Mutation: 2619 from Trp to Gly | Summary: Variants that change residue 2619 from Trp to Gly, Ser, or Cys all resulted in loss of function, indicating a critical role for this residue in molecular function.

Evidence Type: Functional Mutation: 2723 from Asp to Asn | Summary: Variants that change residue 2723 from Asp to Asn, His, Tyr, Ala, Gly, and Val consistently resulted in loss of function, suggesting a negatively charged amino acid is required at this position.

Evidence Type: Functional Mutation: Leu3180 | Summary: Differential effects on function were observed for two alterations in residue Leu3180, where a Pro substitution resulted in loss of function but an Arg substitution resulted in a functional protein.

Evidence Type: Functional Mutation: p.Gly2508Ser | Summary: The variant p.Gly2508Ser is associated with loss of function, indicating its critical role in the molecular function of the protein.

Evidence Type: Functional Mutation: p.Gly2508Arg | Summary: The variant p.Gly2508Arg is associated with loss of function, indicating its critical role in the molecular function of the protein.

Evidence Type: Functional Mutation: p.Ala2603Ser | Summary: The variant p.Ala2603Ser is associated with loss of function, indicating its critical role in the molecular function of the protein.

Evidence Type: Functional Mutation: p.Arg2625Lys | Summary: The variant p.Arg2625Lys is associated with loss of function, indicating its critical role in the molecular function of the protein.

Evidence Type: Functional Mutation: p.Ile2627Val | Summary: The variant p.Ile2627Val is associated with loss of function, indicating its critical role in the molecular function of the protein.

Evidence Type: Functional Mutation: p.Asn3124His | Summary: The variant p.Asn3124His is associated with loss of function, indicating its critical role in the molecular function of the protein.

Evidence Type: Functional Mutation: c.8723T>G | Summary: The variant c.8723T>G (p.Val2908Gly) was evaluated in a functional study and demonstrated sensitivity to multiple drugs, indicating an alteration in molecular function.

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

Gene→Variant (gene-first): NA:2619 from Trp to Gly BRCA2(675):2723 from Asp to Asn NA:Leu3180 BRCA2(675):p.Gly2508Ser APRT(353):p.Gly2508Arg BRCA2(675):p.Ala2603Ser BRCA2(675):p.Arg2625Lys BRCA2(675):p.Ile2627Val BRCA2(675):p.Asn3124His BRCA2(675):c.8723T>G BRCA2(675):c.8905G>A

Genes: NA BRCA2(675) APRT(353)

Variants: 2619 from Trp to Gly 2723 from Asp to Asn Leu3180 p.Gly2508Ser p.Gly2508Arg p.Ala2603Ser p.Arg2625Lys p.Ile2627Val p.Asn3124His c.8723T>G c.8905G>A

[Paper-level Aggregated] PMCID: PMC7820803

Evidence Type(s): Functional

Summary: Mutation: p.Ala636Pro | Summary: The p.Ala636Pro variant is associated with a destabilizing effect on MSH2 protein expression and alters the molecular function of the MMR machinery. It restores 6-TG sensitivity in a functional assay and is linked to a significant depletion of deleterious scores, indicating alterations in molecular or biochemical function.

Gene→Variant (gene-first): MSH2(4436):p.Ala636Pro

Genes: MSH2(4436)

Variants: p.Ala636Pro

[Paper-level Aggregated] PMCID: PMC7820803

Evidence Type(s): Oncogenic

Summary: Mutation: p.Ala636Pro | Summary: The p.Ala636Pro variant is described as a pathogenic founder allele and is associated with MMR deficiency, contributing to tumor development or progression. Its enrichment in mixed cultures and selected cell pools under selective conditions suggests a significant role in tumorigenesis, particularly in the context of bi-allelic MMR loss related to pediatric-onset cancer syndromes such as Lynch syndrome.

Gene→Variant (gene-first): MSH2(4436):p.Ala636Pro

Genes: MSH2(4436)

Variants: p.Ala636Pro

[Paper-level Aggregated] PMCID: PMC7785563

Evidence Type(s): Functional

Summary: Mutation: MSH6 | Summary: The tumor cell-specific loss of MSH6 expression in one case suggests that the mutation alters the molecular function of the MMR pathway, contributing to tumorigenesis.

Gene→Variant (gene-first): NA:MSH6

Genes: NA

Variants: MSH6

[Paper-level Aggregated] PMCID: PMC7785563

Evidence Type(s): Oncogenic

Summary: Mutation: R132H | Summary: The IDH1-R132H mutation is associated with conventional supratentorial IDH-mutant astrocytomas, indicating its role in tumor development or progression.

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

Genes: IDH1(3417)

Variants: R132H

[Paper-level Aggregated] PMCID: PMC7785563

Evidence Type(s): Predisposing

Summary: Mutation: MSH2 (germline) | Summary: The presence of a known deleterious germline MSH2 mutation in cases diagnosed with Lynch syndrome suggests an inherited risk for colorectal cancer.

Evidence Type: Predisposing Mutation: MSH6 (germline) | Summary: The identification of germline mutations in MSH6 in several tumors indicates a hereditary predisposition to MMR-deficiency syndromes, including Lynch syndrome.

Gene→Variant (gene-first): NA:MSH2 (germline) NA:MSH6 (germline)

Genes: NA

Variants: MSH2 (germline) MSH6 (germline)

[Paper-level Aggregated] PMCID: PMC7612475

Evidence Type(s): Functional

Summary: Mutation: K700E | Summary: The SF3B1 K700E mutation alters molecular function by compromising homologous recombination efficiency, inducing unscheduled R-loop formation, and causing replication fork stalling and degradation. It impacts the resolution of Rad51 foci, decreases sister chromatid exchanges, and affects replication fork restart following a transient replication block, leading to increased basal DNA damage and impaired DNA repair processes.

Evidence Type: Functional Mutation: D210N | Summary: The D210N substitution in RNaseH1 alters its ability to resolve R-loops, leading to their accumulation, which is assessed through fluorescence microscopy.

Gene→Variant (gene-first): SF3B1(23451):K700E RNASEH1(246243):D210N

Genes: SF3B1(23451) RNASEH1(246243)

Variants: K700E D210N

[Paper-level Aggregated] PMCID: PMC7612475

Evidence Type(s): Oncogenic

Summary: Mutation: K700E | Summary: The SF3B1 K700E mutation contributes to tumor development by inducing a BRCA-like cellular phenotype, impairing the repair of DNA double-strand breaks, and compromising replication fork stability. It is associated with defects in homologous recombination, increased DNA damage, and slower growth rates of xenografts compared to wild-type. The mutation also confers synthetic lethality to DNA damaging agents and PARP inhibitors, indicating its role in tumor progression.

Evidence Type: Oncogenic Mutation: D210N | Summary: The D210N mutation contributes to the accumulation of R-loops, leading to increased genome instability, which is associated with tumor development.

Gene→Variant (gene-first): SF3B1(23451):K700E RNASEH1(246243):D210N

Genes: SF3B1(23451) RNASEH1(246243)

Variants: K700E D210N

[Paper-level Aggregated] PMCID: PMC7612475

Evidence Type(s): Predictive

Summary: Mutation: K700E | Summary: The K700E mutation in SF3B1 increases cellular sensitivity to ionising radiation and various chemotherapeutic agents, including PARP inhibitors, suggesting a correlation with treatment response. Additionally, the SF3B1K700E mutation is hypothesized to be therapeutically exploitable, as treatment with etoposide or olaparib significantly reduced the volume of tumours with this mutation compared to wild-type tumours.

Gene→Variant (gene-first): SF3B1(23451):K700E

Genes: SF3B1(23451)

Variants: K700E

[Paper-level Aggregated] PMCID: PMC7612117

Evidence Type(s): Functional

Summary: Mutation: p.L1363P | Summary: The Brca1 p.L1363P variant alters molecular or biochemical function by disrupting the interaction with PALB2, impairing homologous recombination repair (HRR), and leading to defects in RAD51 foci formation in response to gamma-radiation. It has been shown to cause general growth defects in embryos and is functionally important as it compromises BRCA1-mediated HRR.

Evidence Type: Functional Mutation: p.L1407P | Summary: The p.L1407P variant disrupts the interaction of BRCA1 with PALB2 and is predicted to disable the alpha-helical structure of the coiled-coil domain, indicating a functional alteration. It is analyzed in the context of its potential phenocopy of p.L1363P, suggesting it may also affect molecular interactions and functions related to BRCA1.

Gene→Variant (gene-first): TP53BP1(7158):p.L1363P BRCA1(672):p.L1407P

Genes: TP53BP1(7158) BRCA1(672)

Variants: p.L1363P p.L1407P

[Paper-level Aggregated] PMCID: PMC7612117

Evidence Type(s): Oncogenic

Summary: Mutation: p.L1363P | Summary: The homozygous Brca1 p.L1363P variant is associated with embryonic lethality and contributes to tumor development or progression, as evidenced by the absence of viable Brca1LP/LP mice, growth defects, and accelerated tumor formation in mouse models. It is implicated in mammary tumor suppression defects and is associated with mammary tumors exhibiting EMT-like phenotypes. Additionally, the p.L1363P variant is linked to the development of carcinosarcomas, indicating its role in oncogenesis and increasing the risk of developing breast cancer.

Gene→Variant (gene-first): TP53BP1(7158):p.L1363P

Genes: TP53BP1(7158)

Variants: p.L1363P

[Paper-level Aggregated] PMCID: PMC7612117

Evidence Type(s): Prognostic

Summary: Mutation: p.L1363P | Summary: The presence of the BRCA1 p.L1363P variant is associated with distinct histopathological features and stable DNA copy number profiles in tumors, which may correlate with disease outcome.

Gene→Variant (gene-first): TP53BP1(7158):p.L1363P

Genes: TP53BP1(7158)

Variants: p.L1363P

[Paper-level Aggregated] PMCID: PMC7612117

Evidence Type(s): Diagnostic

Summary: Mutation: L1363P | Summary: The presence of the KB1(L1363P)P mutation helps define and classify the tumors as carcinosarcomas, distinguishing them from adenocarcinomas based on their histological characteristics.

Gene→Variant (gene-first): TP53BP1(7158):L1363P

Genes: TP53BP1(7158)

Variants: L1363P

[Paper-level Aggregated] PMCID: PMC7612117

Evidence Type(s): Predictive

Summary: Mutation: p.L1363P | Summary: The mutation p.L1363P correlates with increased sensitivity to cisplatin and PARP inhibition, indicating a potential predictive value for therapy response. It is associated with a better response to cisplatin and the PARP inhibitor AZD2461 compared to other tumor types, further supporting its predictive value for therapy response.

Evidence Type: Predictive Mutation: p.L1407P | Summary: The analysis of p.L1407P in relation to p.L1363P implies a similar sensitivity to therapies, indicating a predictive aspect for treatment response.

Gene→Variant (gene-first): TP53BP1(7158):p.L1363P BRCA1(672):p.L1407P

Genes: TP53BP1(7158) BRCA1(672)

Variants: p.L1363P p.L1407P

[Paper-level Aggregated] PMCID: PMC7611203

Evidence Type(s): Oncogenic

Summary: Mutation: c.7355delA | Summary: The mutation c.7355delA in BRCA2 is described as a pathogenic mutation, indicating its contribution to tumor development or progression.

Evidence Type: Oncogenic Mutation: p.C61S | Summary: The BRCA1:p.C61S missense mutation is described as pathogenic, indicating it contributes to tumor development or progression.

Evidence Type: Oncogenic Mutation: p.M1I | Summary: The BRCA1:p.M1I pathogenic mutation is noted to result in loss of the translation start site, suggesting it contributes to tumor development or progression.

Evidence Type: Oncogenic Mutation: c.5946delT | Summary: The BRCA2:c.5946delT mutation is described as pathogenic and is associated with the presentation of neoantigens, indicating its contribution to tumor development.

Evidence Type: Oncogenic Mutation: c.68_69delAG | Summary: The BRCA1:c.68_69delAG mutation is identified as pathogenic and is linked to the generation of neoantigens, suggesting its role in tumor progression.

Evidence Type: Oncogenic Mutation: c.5266dupC | Summary: The BRCA1:c.5266dupC mutation is classified as pathogenic and is associated with neoantigen presentation, indicating its involvement in tumor development.

Gene→Variant (gene-first): BRCA2(675):c.7355delA BRCA1(672):p.C61S BRCA1(672):p.M1I BRCA2(675):c.5946delT BRCA1(672):c.68_69delAG BRCA1(672):c.5266dupC

Genes: BRCA2(675) BRCA1(672)

Variants: c.7355delA p.C61S p.M1I c.5946delT c.68_69delAG c.5266dupC

[Paper-level Aggregated] PMCID: PMC7611203

Evidence Type(s): Diagnostic

Summary: Mutation: c.185delAG | Summary: The BRCA1:c.185delAG mutation is mentioned as a pathogenic mutation used to classify patients in the dataset, indicating its role in defining a disease subtype.

Evidence Type: Diagnostic Mutation: c.5946delT | Summary: The BRCA2:c.5946delT mutation is identified as a common founder mutation in multiple patients, supporting its use in disease classification.

Evidence Type: Diagnostic Mutation: c.6174delT | Summary: The BRCA2:c.6174delT mutation is noted as a pathogenic mutation represented by multiple patients, indicating its role in defining a disease subtype.

Gene→Variant (gene-first): BRCA1(672):c.185delAG BRCA2(675):c.5946delT BRCA2(675):c.6174delT

Genes: BRCA1(672) BRCA2(675)

Variants: c.185delAG c.5946delT c.6174delT

[Paper-level Aggregated] PMCID: PMC7568619

Evidence Type(s): Oncogenic

Summary: Mutation: L1196Q | Summary: The L1196Q mutation is associated with the development of resistance to ALK inhibitors, indicating its role in tumor progression in the context of inflammatory myofibroblastic tumors. This mutation was identified after alectinib resistance developed, leading to the prescription of a newer ALK inhibitor, ceritinib, which resulted in a partial response in the patient.

Gene→Variant (gene-first): ALK(238):L1196Q

Genes: ALK(238)

Variants: L1196Q

[Paper-level Aggregated] PMCID: PMC7568619

Evidence Type(s): Predictive

Summary: Mutation: L1196Q | Summary: The L1196Q mutation in ALK was identified after alectinib resistance developed, leading to the prescription of a newer ALK inhibitor, ceritinib, which resulted in a partial response in the patient.

Gene→Variant (gene-first): ALK(238):L1196Q

Genes: ALK(238)

Variants: L1196Q

[Paper-level Aggregated] PMCID: PMC7545690

Evidence Type(s): Functional

Summary: Mutation: rs3786362 | Summary: The rs3786362 variant is associated with altered expression levels of the TYMS gene, suggesting a functional impact on molecular or biochemical activity in colorectal cancer (CRC) tissues compared to normal tissues.

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

Genes: TYMS(7298)

Variants: rs3786362

[Paper-level Aggregated] PMCID: PMC7545690

Evidence Type(s): Prognostic

Summary: Mutation: rs3786362 | Summary: The SNP rs3786362 in TYMS is correlated with reduced progression-free survival (PFS) and overall survival (OS) in metastatic colorectal cancer (mCRC) patients. The AG genotype is associated with worse outcomes compared to the AA genotype, and carriers of the G allele are prone to shorter survival times. This variant indicates its potential role as a prognostic marker for disease outcome independent of therapy, particularly in specific subgroups of mCRC patients.

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

Genes: TYMS(7298)

Variants: rs3786362

[Paper-level Aggregated] PMCID: PMC7545690

Evidence Type(s): Predictive

Summary: Mutation: rs3786362 | Summary: The variant rs3786362 in TYMS correlates with the disease control rate (DCR) in metastatic colorectal cancer (mCRC) patients, with the G allele associated with reduced DCR in those undergoing first-line chemotherapy. It may serve as a predictive biomarker for survival in mCRC patients, particularly in certain subgroups, suggesting a correlation with treatment response or outcomes.

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

Genes: TYMS(7298)

Variants: rs3786362

[Paper-level Aggregated] PMCID: PMC7499606

Evidence Type(s): Oncogenic

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

Gene→Variant (gene-first): TP53(7157):Y220C

Genes: TP53(7157)

Variants: Y220C

[Paper-level Aggregated] PMCID: PMC7472556

Evidence Type(s): nan

Summary: No positive paragraphs to aggregate.

Gene→Variant (gene-first):

Genes:

Variants:

[Paper-level Aggregated] PMCID: PMC7467277

Evidence Type(s): Oncogenic

Summary: Mutation: chr8:208343-27992852 | Summary: The deletion observed on chromosome 8p, specifically spanning the region chr8:208343-27992852, is classified as a somatic copy number alteration (CNA) that contributes to tumor development or progression.

Gene→Variant (gene-first): NA:chr8:208343-27992852

Genes: NA

Variants: chr8:208343-27992852

[Paper-level Aggregated] PMCID: PMC7362646

Evidence Type(s): Oncogenic

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

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

Genes: IDH1(3417)

Variants: p.R132H

[Paper-level Aggregated] PMCID: PMC7342819

Evidence Type(s): Oncogenic

Summary: Mutation: p.G12V | Summary: The KRAS p.G12V mutation is identified as a common driver mutation contributing to tumor development in the context of pancreatic adenocarcinoma (PAAD).

Evidence Type: Oncogenic Mutation: c.2514+1G>C | Summary: The somatic mutation c.2514+1G>C in PALB2 is associated with tumor development or progression, contributing to the patient's pancreatic cancer and is noted as likely contributing to tumor progression, associated with a deficiency in DNA homologous recombination.

Gene→Variant (gene-first): KRAS(3845):p.G12V PALB2(79728):c.2514+1G>C

Genes: KRAS(3845) PALB2(79728)

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

[Paper-level Aggregated] PMCID: PMC7342819

Evidence Type(s): Predisposing

Summary: Mutation: c.3114-1G>A | Summary: The PALB2 c.3114-1G>A mutation is described as a germline mutation detected in peripheral blood cells, indicating an inherited risk for disease and a predisposition to cancer in this patient.

Gene→Variant (gene-first): PALB2(79728):c.3114-1G>A

Genes: PALB2(79728)

Variants: c.3114-1G>A

[Paper-level Aggregated] PMCID: PMC7325368

Evidence Type(s): Oncogenic

Summary: Mutation: B-RAFV600E | Summary: The B-RAFV600E mutation contributes to tumor development and progression in various cancers, including melanoma and thyroid cancer, as indicated by its presence in these cancer types and the observed treatment responses in patients.

Evidence Type: Oncogenic Mutation: G13D | Summary: The K-RAS G13D mutation contributes to tumor development or progression, as it is part of the K-RAS mutations observed in patients with endometrial cancer and NSCLC.

Gene→Variant (gene-first): BRAF(673):B-RAFV600E KRAS(3845):G13D

Genes: BRAF(673) KRAS(3845)

Variants: B-RAFV600E G13D

[Paper-level Aggregated] PMCID: PMC7325368

Evidence Type(s): Predictive

Summary: Mutation: B-RAFV600E | Summary: The B-RAFV600E mutation is associated with responses to therapy, including partial responses (PR) and stable disease (SD) in clinical studies. It is also linked to treatment sensitivity in patients with B-RAF-mutated solid tumors, including melanoma, thyroid cancer, and low-grade serous ovarian cancer.

Evidence Type: Predictive Mutation: G13D | Summary: The K-RAS G13D mutation is associated with treatment response, as patients with K-RAS mutations, including G13D, had confirmed responses and stable disease (SD) in the context of therapy.

Gene→Variant (gene-first): BRAF(673):B-RAFV600E KRAS(3845):G13D

Genes: BRAF(673) KRAS(3845)

Variants: B-RAFV600E G13D

[Paper-level Aggregated] PMCID: PMC7302243

Evidence Type(s): Oncogenic

Summary: Mutation: T790M | Summary: The T790M mutation contributes to tumor progression by conferring resistance to targeted therapies in the context of EGFR-driven cancer, indicating its role in treatment response.

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

Genes: EGFR(1956)

Variants: T790M

[Paper-level Aggregated] PMCID: PMC7302243

Evidence Type(s): Predictive

Summary: Mutation: T790M | Summary: The T790M mutation is associated with acquired resistance to EGFR-TKI therapy in PC9/GR cells, indicating its role in treatment response.

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

Genes: EGFR(1956)

Variants: T790M

[Paper-level Aggregated] PMCID: PMC7294133

Evidence Type(s): Functional

Summary: Mutation: V871I | Summary: The EPHB4-V871I variant does not impair EPHB4 expression at the mRNA and protein levels, but alters molecular function related to cellular proliferation and migration in neuroblastoma (NB) cell lines. It is associated with increased propagation rates, enhanced migration properties in wound-healing experiments, and a higher number of colonies formed in soft agar assays compared to wild type and empty vector controls. Additionally, the variant increases the expression of downstream target genes and enhances phosphorylation of the ERK1-2 pathway, indicating a significant alteration in molecular or biochemical processes.

Gene→Variant (gene-first): EPHB4(2050):V871I

Genes: EPHB4(2050)

Variants: V871I

[Paper-level Aggregated] PMCID: PMC7294133

Evidence Type(s): Oncogenic

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

Evidence Type: Oncogenic Mutation: V871I | Summary: The V871I variant in the EPHB4 gene contributes to tumor development and progression in neuroblastoma by increasing proliferation, migration, and invasion properties in cancer cell lines. It is associated with a high pathogenic score and impacts downstream signaling pathways and gene expression, indicating its role in tumor development or progression.

Gene→Variant (gene-first): ALK(238):F1174L EPHB4(2050):V871I

Genes: ALK(238) EPHB4(2050)

Variants: F1174L V871I

[Paper-level Aggregated] PMCID: PMC7294133

Evidence Type(s): Prognostic

Summary: Mutation: V871I | Summary: Higher expression of EPHB4, associated with the V871I variant, correlates with advanced disease stages and poor overall survival in neuroblastoma patients.

Gene→Variant (gene-first): EPHB4(2050):V871I

Genes: EPHB4(2050)

Variants: V871I

[Paper-level Aggregated] PMCID: PMC7294133

Evidence Type(s): Diagnostic

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

Gene→Variant (gene-first): EPHB4(2050):V871I

Genes: EPHB4(2050)

Variants: V871I

[Paper-level Aggregated] PMCID: PMC7294133

Evidence Type(s): Predictive

Summary: Mutation: V871I | Summary: The variant EPHB4-V871I is associated with a response to treatment with TK inhibitors, indicating its predictive value in therapy sensitivity. Additionally, the use of EPHB4 inhibitors, which target the effects of the V871I variant, suggests potential therapeutic strategies for neuroblastoma patients.

Gene→Variant (gene-first): EPHB4(2050):V871I

Genes: EPHB4(2050)

Variants: V871I

[Paper-level Aggregated] PMCID: PMC7293710

Evidence Type(s): Oncogenic

Summary: Mutation: G12V | Summary: The KRASG12V mutation contributes to tumor development and progression, as it is involved in the context of cancer cell viability and response to therapy.

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

Genes: KRAS(3845)

Variants: G12V

[Paper-level Aggregated] PMCID: PMC7293710

Evidence Type(s): Predictive

Summary: Mutation: G12V | Summary: The KRASG12V mutation is associated with increased sensitivity to the antiproliferation therapy of metformin in colorectal cancer cell lines, indicating a predictive relationship with treatment response.

Evidence Type: Predictive

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

Genes: KRAS(3845)

Variants: G12V

[Paper-level Aggregated] PMCID: PMC7226056

Evidence Type(s): Oncogenic

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

Gene→Variant (gene-first): NA:TERT mutation

Genes: NA

Variants: TERT mutation

[Paper-level Aggregated] PMCID: PMC7211323

Evidence Type(s): Functional

Summary: Mutation: c.285delA | Summary: The mutation c.285delA results in no detectable protein band, indicating that it alters the molecular function of the ACVR2A gene product, likely leading to degradation through nonsense-mediated decay.

Evidence Type: Functional Mutation: 1310AA | Summary: The mutation 1310AA is associated with the production of truncated ACVR2A protein, suggesting that it alters the molecular function of the ACVR2A gene product.

Gene→Variant (gene-first): ACVR2A(92):c.285delA ACVR2A(92):1310AA

Genes: ACVR2A(92)

Variants: c.285delA 1310AA

[Paper-level Aggregated] PMCID: PMC7211323

Evidence Type(s): Oncogenic

Summary: Mutation: 1310delA | Summary: The mutation 1310delA is identified as a hotspot mutation in the ACVR2A gene, contributing to tumor development in gastric cancer patients.

Evidence Type: Oncogenic Mutation: c.1309-1310delAA | Summary: The mutation c.1309-1310delAA is a hotspot mutation in the ACVR2A gene, associated with tumor progression in gastric cancer.

Evidence Type: Oncogenic Mutation: c.285delA | Summary: The mutation c.285delA is recognized as a hotspot mutation in the ACVR2A gene, playing a role in the development of gastric cancer.

Evidence Type: Oncogenic Mutation: p. D96Tfs54 | Summary: The mutation p. D96Tfs54 is a frameshift mutation in the ACVR2A gene, contributing to oncogenic processes in gastric cancer.

Gene→Variant (gene-first): ACVR2A(92):1310delA ACVR2A(92):c.1309-1310delAA ACVR2A(92):c.285delA ACVR2A(92):p. D96Tfs*54

Genes: ACVR2A(92)

Variants: 1310delA c.1309-1310delAA c.285delA p. D96Tfs*54

[Paper-level Aggregated] PMCID: PMC7211323

Evidence Type(s): Diagnostic

Summary: Mutation: 1309-1310delAA | Summary: The mutation 1309-1310delAA is associated with the MSI-H subtype of gastric cancers, indicating its role in classifying the disease.

Evidence Type: Diagnostic Mutation: c.1310delA | Summary: The mutation c.1310delA is linked to the MSI-H subtype of gastric cancers, supporting its use in disease classification.

Evidence Type: Diagnostic Mutation: c.285delA | Summary: The mutation c.285delA is associated with the MSI-H subtype of gastric cancers, indicating its relevance in disease classification.

Gene→Variant (gene-first): ACVR2A(92):1309-1310delAA ACVR2A(92):c.1310delA ACVR2A(92):c.285delA

Genes: ACVR2A(92)

Variants: 1309-1310delAA c.1310delA c.285delA

[Paper-level Aggregated] PMCID: PMC7190743

Evidence Type(s): Functional

Summary: Mutation: C124S | Summary: The C124S variant is characterized as catalytically inactive for both protein and lipid phosphatase functions, showing complete loss of function (LoF) indistinguishable from GFP controls in terms of PSD95 density. It alters molecular function by raising pAKT/AKT levels, consistent with a dominant negative phenotype, and is involved in genetic interactions that alter PI3P metabolism, indicating a significant alteration in molecular function.

Evidence Type: Functional Mutation: G129E | Summary: The G129E variant is described as a lipid phosphatase-dead variant and alters molecular function by raising pAKT/AKT levels, consistent with a dominant negative phenotype. It exhibited eclosion significantly faster than the empty vector control, suggesting a functional change in its activity.

Evidence Type: Functional Mutation: Y138L | Summary: Y138L is identified as a protein phosphatase-dead variant, indicating a change in the molecular function of the PTEN protein.

Evidence Type: Functional Mutation: N117S | Summary: The N117S variant slowed the developmental rate further than the wild-type, indicating a functional alteration in its role.

Evidence Type: Functional Mutation: Q298E | Summary: The Q298E variant also slowed the developmental rate further than the wild-type, suggesting a functional change in its activity.

Evidence Type: Functional Mutation: A79T | Summary: The A79T variant exhibited a gain-of-function (GoF) phenotype in axonal growth and altered PSD95 density and dendrite length, indicating a change in molecular function. It retained wild-type-like function in the context of chemotaxis assays in C. elegans.

Evidence Type: Functional Mutation: I101T | Summary: The I101T variant, along with C124S, increased soma size more than GFP, suggesting a change in molecular function related to neuronal growth.

Evidence Type: Functional Mutation: G132D | Summary: The G132D variant exhibited stronger negative chemotaxis than daf-18 mutants and increased soma size more than GFP, indicating a functional alteration associated with neuronal growth.

Evidence Type: Functional Mutation: D268E | Summary: The D268E variant showed partial loss of function (LoF) in the chemotaxis assays in daf-18 mutant worms and appeared wild-type-like in all measures of growth and synaptogenesis, suggesting it does not alter molecular function significantly.

Evidence Type: Functional Mutation: T167N | Summary: The T167N variant showed partial loss of function (LoF) in the chemotaxis assays in daf-18 mutant worms.

Evidence Type: Functional Mutation: Y176C | Summary: The Y176C variant showed partial loss of function (LoF) in the chemotaxis assays in daf-18 mutant worms.

Evidence Type: Functional Mutation: H93Y | Summary: The H93Y variant is associated with altered molecular function, specifically reduced protein stability compared to wild-type PTEN.

Evidence Type: Functional Mutation: P354Q | Summary: The P354Q variant retained wild-type-like function in the context of chemotaxis assays in C. elegans and does not show significant differences in protein stability compared to wild-type PTEN, indicating it may not alter molecular function.

Evidence Type: Functional Mutation: R130L | Summary: The R130L variant alters molecular function by exhibiting a change in stability between parental and PTEN-KO cells, suggesting its interaction with endogenous PTEN has minimal influence and does not show significant differences in protein stability compared to wild-type PTEN.

Evidence Type: Functional Mutation: R14G | Summary: The R14G variant does not show significant differences in protein stability compared to wild-type PTEN, indicating it may not alter molecular function.

Evidence Type: Functional Mutation: R15S | Summary: The R15S variant does not show significant differences in protein stability compared to wild-type PTEN, indicating it may not alter molecular function.

Evidence Type: Functional Mutation: T78A | Summary: The T78A variant does not show significant differences in protein stability compared to wild-type PTEN, indicating it may not alter molecular function.

Evidence Type: Functional Mutation: A126D | Summary: The A126D variant alters molecular function by exhibiting a change in stability between parental and PTEN-KO cells, suggesting its interaction with endogenous PTEN has minimal influence.

Evidence Type: Functional Mutation: A126P | Summary: The A126P variant alters molecular function by exhibiting a change in stability between parental and PTEN-KO cells, indicating its interaction with endogenous PTEN has minimal influence.

Evidence Type: Functional Mutation: H123Q | Summary: The H123Q variant alters molecular function by exhibiting a change in stability between parental and PTEN-KO cells, suggesting its interaction with endogenous PTEN has minimal influence.

Evidence Type: Functional Mutation: P38H | Summary: The P38H variant alters molecular function by exhibiting a change in stability between parental and PTEN-KO cells, indicating its interaction with endogenous PTEN has minimal influence.

Evidence Type: Functional Mutation: R130Q | Summary: The R130Q variant alters molecular function by exhibiting a change in stability between parental and PTEN-KO cells, indicating its interaction with endogenous PTEN has minimal influence.

Gene→Variant (gene-first): PTEN(5728):C124S PTEN(5728):G129E PTEN(5728):Y138L PTEN(5728):N117S PTEN(5728):Q298E PTEN(5728):A79T PTEN(5728):I101T PTEN(5728):G132D PTEN(5728):D268E PTEN(5728):T167N PTEN(5728):Y176C PTEN(5728):H93Y PTEN(5728):P354Q PTEN(5728):R130L PTEN(5728):R14G PTEN(5728):R15S PTEN(5728):T78A PTEN(5728):A126D PTEN(5728):A126P PTEN(5728):H123Q PTEN(5728):P38H PTEN(5728):R130Q

Genes: PTEN(5728)

Variants: C124S G129E Y138L N117S Q298E A79T I101T G132D D268E T167N Y176C H93Y P354Q R130L R14G R15S T78A A126D A126P H123Q P38H R130Q

[Paper-level Aggregated] PMCID: PMC7190743

Evidence Type(s): Oncogenic

Summary: Mutation: C124S | Summary: C124S has been found in somatic cancer, suggesting it contributes to tumor development or progression.

Evidence Type: Oncogenic Mutation: R130X | Summary: R130X is associated with somatic cancer, indicating its role in tumor development or progression.

Evidence Type: Oncogenic Mutation: R335X | Summary: R335X is commonly associated with somatic cancer, suggesting it contributes to tumor development or progression.

Evidence Type: Oncogenic Mutation: P354Q | Summary: The variant P354Q is classified as Pathogenic, indicating it contributes to tumor development or progression.

Evidence Type: Oncogenic Mutation: T202I | Summary: The variant T202I is classified as Pathogenic, indicating it contributes to tumor development or progression.

Evidence Type: Oncogenic Mutation: T78A | Summary: The variant T78A is classified as Pathogenic, indicating it contributes to tumor development or progression.

Evidence Type: Oncogenic Mutation: I135V | Summary: The variant I135V is classified as Likely Pathogenic, indicating it contributes to tumor development or progression.

Evidence Type: Oncogenic Mutation: N340H | Summary: The variant N340H is classified as Likely Pathogenic, indicating it contributes to tumor development or progression.

Evidence Type: Oncogenic Mutation: N356D | Summary: The variant N356D is classified as Likely Pathogenic, indicating it contributes to tumor development or progression.

Evidence Type: Oncogenic Mutation: K402N | Summary: The variant K402N is classified as Likely Pathogenic, indicating it contributes to tumor development or progression.

Evidence Type: Oncogenic Mutation: N117S | Summary: The variant N117S is classified as Likely Pathogenic, indicating it contributes to tumor development or progression.

Evidence Type: Oncogenic Mutation: Y180H | Summary: The variant Y180H is classified as Likely Pathogenic, indicating it contributes to tumor development or progression.

Evidence Type: Oncogenic Mutation: I203V | Summary: The variant I203V is classified as Likely Pathogenic, indicating it contributes to tumor development or progression.

Evidence Type: Oncogenic Mutation: Q298E | Summary: The variant Q298E is classified as Likely Pathogenic, indicating it contributes to tumor development or progression.

Evidence Type: Oncogenic Mutation: N340D | Summary: The variant N340D is classified as Likely Pathogenic, indicating it contributes to tumor development or progression.

Evidence Type: Oncogenic Mutation: K342N | Summary: The variant K342N is classified as Likely Pathogenic, indicating it contributes to tumor development or progression.

Evidence Type: Oncogenic Mutation: L345V | Summary: The variant L345V is classified as Likely Pathogenic, indicating it contributes to tumor development or progression.

Evidence Type: Oncogenic Mutation: I400V | Summary: The variant I400V is classified as Likely Pathogenic, indicating it contributes to tumor development or progression.

Gene→Variant (gene-first): PTEN(5728):C124S PTEN(5728):R130X PTEN(5728):R335X PTEN(5728):P354Q PTEN(5728):T202I PTEN(5728):T78A PTEN(5728):I135V PTEN(5728):N340H PTEN(5728):N356D PTEN(5728):K402N PTEN(5728):N117S PTEN(5728):Y180H PTEN(5728):I203V PTEN(5728):Q298E PTEN(5728):N340D PTEN(5728):K342N PTEN(5728):L345V PTEN(5728):I400V

Genes: PTEN(5728)

Variants: C124S R130X R335X P354Q T202I T78A I135V N340H N356D K402N N117S Y180H I203V Q298E N340D K342N L345V I400V

[Paper-level Aggregated] PMCID: PMC7182441

Evidence Type(s): Functional

Summary: Mutation: S6 | Summary: The variant S6 is involved in the molecular function related to mTOR signaling and autophagy in response to amino acid starvation, as indicated by the effects of alpha-MT on the phosphorylation status of S6 kinase in LS174T cells.

Gene→Variant (gene-first): RPS6KB1(6198):S6

Genes: RPS6KB1(6198)

Variants: S6