[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: 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: 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

[Paragraph-level] PMCID: PMC11272140 Section: RESULTS PassageIndex: 10

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: G2032R | Summary: The G2032R mutation is identified as a ROS1 resistance mutation in crizotinib-pretreated patients, indicating its role in tumor progression and resistance to therapy. Evidence Type: Oncogenic | Mutation: L2026M | Summary: The L2026M mutation is also 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): 6098:G2032R 4914:G2101A 7294:L2026M 7294:S1986F

Genes: 6098 4914 7294

Variants: G2032R G2101A L2026M S1986F

[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: 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: 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: 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

[Paragraph-level] PMCID: PMC10524391 Section: ABSTRACT PassageIndex: 6

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: C797S | Summary: The C797S mutation is associated with resistance to osimertinib, indicating its predictive value in therapy response. Evidence Type: Oncogenic | Mutation: C797S | Summary: The C797S mutation contributes to tumor progression in the context of EGFR-mutant lung cancers. Evidence Type: Oncogenic | Mutation: G12S | Summary: The G12S mutation is implicated in tumor development as part of off-target resistance mechanisms. Evidence Type: Oncogenic | Mutation: G810S | Summary: The G810S mutation is associated with tumor progression in RET fusion-positive lung cancers. Evidence Type: Oncogenic | Mutation: T790M | Summary: The T790M mutation is known to contribute to tumor development and resistance in EGFR-mutant lung cancers. Evidence Type: Oncogenic | Mutation: V600E | Summary: The V600E mutation is recognized for its role in tumor progression as part of off-target resistance mechanisms.

Gene→Variant (gene-first): 1956:C797S 3845:G12S 5979:G810S 1956:T790M 673:V600E

Genes: 1956 3845 5979 673

Variants: C797S G12S G810S T790M V600E

[Paragraph-level] PMCID: PMC10524391 Section: RESULTS PassageIndex: 26

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: C797S | Summary: The EGFR C797S mutation is associated with resistance mechanisms, indicating its potential role in treatment response. Evidence Type: Oncogenic | Mutation: V600E | Summary: The BRAF V600E mutation is implicated in tumor development and progression, contributing to oncogenic processes. 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: V804M | Summary: The RET V804M mutation is also linked to tumor development, supporting its classification as an oncogenic variant. Evidence Type: Oncogenic | Mutation: G12S | Summary: The KRAS G12S mutation is recognized for its contribution to tumor development, marking it as an oncogenic variant. Evidence Type: Oncogenic | Mutation: G810S | Summary: The RET G810S mutation is associated with tumor progression, reinforcing its role as an oncogenic driver.

Gene→Variant (gene-first): 1956:C797S 3845:G12S 5979:G810S 673:V600E 5979:V804E 5979:V804M

Genes: 1956 3845 5979 673

Variants: C797S G12S G810S V600E V804E V804M

[Paragraph-level] PMCID: PMC10524391 Section: RESULTS PassageIndex: 25

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: G12S | Summary: The KRAS G12S mutation is associated with tumor development or progression as it is mentioned in the context of off-target resistance involving receptor tyrosine kinase or MAPK pathway activation. Evidence Type: Oncogenic | Mutation: V600E | Summary: The BRAF V600E mutation is identified as a hotspot mutation contributing to tumor development or progression, as indicated by its presence in cases of off-target resistance.

Gene→Variant (gene-first): 3845:G12S 673:V600E

Genes: 3845 673

Variants: G12S V600E

[Paragraph-level] PMCID: PMC10524391 Section: RESULTS PassageIndex: 24

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: G810S | Summary: The acquired RET G810S mutation is noted in the context of tumor progression, suggesting its contribution to tumor development or progression.

Gene→Variant (gene-first): 5979:G810S

Genes: 5979

Variants: G810S

[Paragraph-level] PMCID: PMC10524391 Section: RESULTS PassageIndex: 23

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: C797S | Summary: The C797S mutation is associated with resistance to therapeutic EGFR engagement, indicating its role in treatment response. Evidence Type: Predictive | Mutation: T790M | Summary: The T790M mutation is implicated in resistance to therapeutic EGFR engagement, suggesting its relevance in treatment response. Evidence Type: Oncogenic | Mutation: C797S | Summary: The C797S mutation contributes to tumor development or progression as a resistance mutation in EGFR. Evidence Type: Oncogenic | Mutation: T790M | Summary: The T790M mutation is a resistance mutation that contributes to tumor development or progression in EGFR. Evidence Type: Oncogenic | Mutation: V804M/E | Summary: The V804M/E mutations are identified as gatekeeper mutations that contribute to tumor development or progression in RET. Evidence Type: Oncogenic | Mutation: G810S | Summary: The G810S mutation is a solvent front mutation that contributes to tumor development or progression in RET.

Gene→Variant (gene-first): 1956:C797S 5979:G810S 1956:T790M 5979:V804M/E

Genes: 1956 5979

Variants: C797S G810S T790M V804M/E

[Paragraph-level] PMCID: PMC10524391 Section: RESULTS PassageIndex: 9

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: T790M | Summary: The EGFR T790M mutation is associated with resistance to earlier generation EGFR TKIs, indicating its predictive role in therapy response when patients are treated with osimertinib. Evidence Type: Oncogenic | Mutation: T790M | Summary: The EGFR T790M mutation contributes to tumor progression and is recognized as an oncogenic variant in the context of acquired resistance to EGFR-targeted therapies.

Gene→Variant (gene-first): 1956:T790M

Genes: 1956

Variants: T790M

[Paragraph-level] PMCID: PMC10524391 Section: RESULTS PassageIndex: 8

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: T790M | Summary: The T790M mutation is associated with tumor development and progression, as it is found in a significant proportion of tumors alongside other mutations. 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.

Gene→Variant (gene-first): 1956:L747S 1956:L858R 1956:T790M

Genes: 1956

Variants: L747S L858R T790M

[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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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

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

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: T790M | Summary: The T790M mutation is associated with a favorable clinical response to Abivertinib therapy in patients with NSCLC, indicating its predictive value for treatment efficacy. Evidence Type: Oncogenic | Mutation: T790M | Summary: The T790M mutation contributes to tumor development and progression in non-small cell lung cancer (NSCLC), highlighting its oncogenic role.

Gene→Variant (gene-first): 1956:T790M

Genes: 1956

Variants: T790M

[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

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

Evidence Type(s): Predictive, Oncogenic, Prognostic

Summary: Evidence Type: Predictive | Mutation: V600E | Summary: The BRAF V600E mutation is associated with a confirmed response to therapy, as evidenced by a high overall response rate (ORR) in patients with this mutation. Evidence Type: Oncogenic | Mutation: V600E | Summary: The BRAF V600E mutation contributes to tumor development or progression, as it is identified in patients with BRAF V600E-mutant disease. Evidence Type: Prognostic | Mutation: V600E | Summary: The presence of the BRAF V600E mutation correlates with disease outcome, as indicated by the median duration of response (DOR) in patients with this mutation.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

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

Evidence Type(s): Oncogenic, Diagnostic

Summary: Evidence Type: Oncogenic | Mutation: V600E | Summary: The BRAF V600E mutation is confirmed in a significant portion of patients with advanced thyroid cancer, indicating its role in tumor development or progression. Evidence Type: Diagnostic | Mutation: V600E | Summary: The presence of the BRAF V600E mutation is used to confirm the diagnosis of advanced thyroid cancer in the patient cohort.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[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: 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: 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: 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

[Paragraph-level] PMCID: PMC8453302 Section: ABSTRACT PassageIndex: 2

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | 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: Oncogenic | 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): 2064:G292R

Genes: 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: 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: 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: 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: 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: 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: 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: 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

[Paragraph-level] PMCID: PMC8033310 Section: RESULTS PassageIndex: 6

Evidence Type(s): Predictive, Oncogenic, Functional

Summary: Evidence Type: Predictive | Mutation: E545K | Summary: The PIK3CA E545K mutation is associated with induced resistance to chemotherapy in TNBC cells, suggesting a correlation with treatment response. Evidence Type: Oncogenic | Mutation: E545K | Summary: The PIK3CA E545K mutation contributes to tumor development and progression, as indicated by the increased tumor volume in experimental models. Evidence Type: Functional | Mutation: E545K | Summary: The PIK3CA E545K mutation alters molecular function by downregulating Caspase 3 and upregulating Xiap in tumor tissues, affecting apoptosis.

Gene→Variant (gene-first): 5290:E545K

Genes: 5290

Variants: E545K

[Paragraph-level] PMCID: PMC8033310 Section: RESULTS PassageIndex: 5

Evidence Type(s): Oncogenic, Predictive

Summary: Evidence Type: Oncogenic | Mutation: E545K | Summary: The PIK3CA E545K mutation is associated with promoting growth and inhibiting apoptosis in TNBC cell lines, indicating its role in tumor development and progression. Evidence Type: Predictive | Mutation: E545K | Summary: The presence of the PIK3CA E545K mutation correlates with decreased sensitivity to chemotherapy, suggesting it may influence treatment response in TNBC patients.

Gene→Variant (gene-first): 5290:E545K

Genes: 5290

Variants: E545K

[Paragraph-level] PMCID: PMC8033310 Section: RESULTS PassageIndex: 3

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: E545K | Summary: The PIK3CAE545K mutation was shown to alter cell viability and apoptosis in TNBC cell lines, indicating a change in molecular function related to cell proliferation and survival. Evidence Type: Oncogenic | Mutation: E545K | Summary: The PIK3CAE545K mutation contributes to tumor development by enhancing the aggressiveness and migratory phenotype of TNBC cells.

Gene→Variant (gene-first): 5290:E545K

Genes: 5290

Variants: E545K

[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): 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: 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: 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: 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: 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: 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: 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: 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: 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: 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

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

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

Summary: 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. Evidence Type: Functional | Mutation: V871I | Summary: The V871I variant alters molecular function by affecting the phosphorylation of the ERK1-2 pathway and influencing the expression of target genes related to cancer progression. Evidence Type: Prognostic | Mutation: V871I | Summary: Higher expression of EPHB4, associated with the V871I variant, correlates with advanced disease stages and poor overall survival in neuroblastoma patients. Evidence Type: Predictive | Mutation: V871I | Summary: The use of EPHB4 inhibitors, which target the effects of the V871I variant, suggests potential therapeutic strategies for neuroblastoma patients.

Gene→Variant (gene-first): 2050:V871I

Genes: 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: 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): 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

[Paragraph-level] PMCID: PMC7211323 Section: RESULTS PassageIndex: 9

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | 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): 92:1310delA 92:c.1309-1310delAA 92:c.285delA 92:p. D96Tfs*54

Genes: 92

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

[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: PMC7086303

Evidence Type(s): Oncogenic

Summary: Mutation: G598V | Summary: The G598V mutation is described as an activating mutation in EGFR, contributing to tumor development and progression in BTSC cultures.

Gene→Variant (gene-first): EGFR(1956):G598V

Genes: EGFR(1956)

Variants: G598V

[Paper-level Aggregated] PMCID: PMC7081042

Evidence Type(s): Oncogenic

Summary: Mutation: L755S | Summary: The L755S mutation in HER2 is associated with resistance to trastuzumab, indicating its role in oncogenic processes related to tumor progression.

Evidence Type: Oncogenic Mutation: V842I | Summary: The V842I mutation in HER2 is linked to resistance to trastuzumab, suggesting its contribution to oncogenic behavior in tumor development.

Evidence Type: Oncogenic Mutation: K753I | Summary: The K753I mutation in HER2 is associated with resistance to trastuzumab, indicating its role in oncogenic processes related to tumor progression.

Evidence Type: Oncogenic Mutation: D769Y | Summary: The D769Y mutation in HER2 is linked to resistance to trastuzumab, suggesting its contribution to oncogenic behavior in tumor development.

Gene→Variant (gene-first): ERBB2(2064):L755S ERBB2(2064):V842I EGFR(1956):K753I ERBB2(2064):D769Y

Genes: ERBB2(2064) EGFR(1956)

Variants: L755S V842I K753I D769Y

[Paper-level Aggregated] PMCID: PMC7068240

Evidence Type(s): Oncogenic

Summary: Mutation: V600E | Summary: The BRAF V600E mutation is associated with tumor development and progression in colorectal cancer (CRC), including its presence in CRC specimens and its correlation with miR-31 expression levels. It contributes to tumor development in non-MSI tumors and is recognized as an oncogenic variant in this cancer type.

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

Genes: BRAF(673)

Variants: V600E

[Paper-level Aggregated] PMCID: PMC7064492

Evidence Type(s): Oncogenic

Summary: Mutation: p.K57N | Summary: The MAP2K1 mutation p.K57N is associated with the development of arteriovenous malformation (AVM) through its presence in endothelial cells, indicating its role in tumor progression. This mutation was found in tissue adjacent to the cartilage in patients with auricular AVM, further suggesting its potential role in tumor development or progression.

Gene→Variant (gene-first): MAP2K1(5604):p.K57N

Genes: MAP2K1(5604)

Variants: p.K57N

[Paragraph-level] PMCID: PMC7064492 Section: RESULTS PassageIndex: 2

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: p.K57N | Summary: The MAP2K1 (p.K57N) mutation was found in the tissue adjacent to the cartilage in patients with auricular AVM, indicating its potential role in tumor development or progression. Evidence Type: Functional | Mutation: p.K57N | Summary: The presence of the MAP2K1 (p.K57N) mutation suggests alterations in molecular or biochemical function, as indicated by its enrichment in endothelial cells compared to non-endothelial cells.

Gene→Variant (gene-first): 5604:p.K57N

Genes: 5604

Variants: p.K57N

[Paper-level Aggregated] PMCID: PMC6938308

Evidence Type(s): Oncogenic

Summary: Mutation: p.12G | Summary: The somatic mutation p.12G in KRAS has been linked to brain AVMs, indicating its contribution to tumor development.

Evidence Type: Oncogenic Mutation: p.600V | Summary: The somatic mutation p.600V in BRAF has been linked to brain AVMs, indicating its contribution to tumor development.

Evidence Type: Oncogenic Mutation: p.G12D | Summary: The somatic mutation p.G12D in KRAS has been identified in multiple AVM specimens, suggesting its role in tumor progression. The G12D mutation is also a somatic variant that contributes to tumor development or progression, as indicated by its presence in specimens with confirmed mutations.

Evidence Type: Oncogenic Mutation: p.G12V | Summary: The somatic mutation p.G12V in KRAS has been identified in multiple AVM specimens, suggesting its role in tumor progression. The G12V mutation is also a somatic variant that contributes to tumor development or progression, as indicated by its presence in specimens with confirmed mutations.

Evidence Type: Oncogenic Mutation: p.Q636X | Summary: The somatic mutation p.Q636X in BRAF has been linked to brain AVMs, indicating its contribution to tumor development. The Q636X mutation is also a somatic variant that contributes to tumor development or progression, as indicated by its presence in specimens with confirmed mutations.

Evidence Type: Oncogenic Mutation: p.V600E | Summary: The somatic mutation p.V600E in BRAF has been linked to brain AVMs, indicating its contribution to tumor development. The V600E mutation is also a somatic variant that contributes to tumor development or progression, as indicated by its presence in specimens with confirmed mutations.

Gene→Variant (gene-first): KRAS(3845):p.12G BRAF(673):p.600V KRAS(3845):p.G12D KRAS(3845):p.G12V BRAF(673):p.Q636X BRAF(673):p.V600E

Genes: KRAS(3845) BRAF(673)

Variants: p.12G p.600V p.G12D p.G12V p.Q636X p.V600E

[Paper-level Aggregated] PMCID: PMC6843359

Evidence Type(s): Oncogenic

Summary: Mutation: S310F | Summary: The S310F mutation is associated with tumor development or progression, as it alters the molecular function of HER2, contributes to receptor activation, and is involved in the formation of active heterodimers with EGFR. Its expression in bladder cancer cell lines suggests a role in tumor development, and it is implicated in altered reactivity to therapeutic antibodies.

Evidence Type: Oncogenic Mutation: G309A | Summary: The G309A mutation is associated with receptor activation in the HER2 extracellular domain, indicating its role in tumor development.

Evidence Type: Oncogenic Mutation: G309E | Summary: The G309E mutation contributes to receptor activation in the HER2 extracellular domain, suggesting its involvement in tumor progression.

Evidence Type: Oncogenic Mutation: S310 | Summary: The S310 mutation is implicated in receptor activation within the HER2 extracellular domain, indicating its potential role in oncogenesis.

Evidence Type: Oncogenic Mutation: S310Y | Summary: The S310Y mutation is associated with receptor activation in the HER2 extracellular domain, indicating its role in tumor progression.

Gene→Variant (gene-first): ERBB2(2064):S310F ERBB2(2064):G309A ERBB2(2064):G309E ERBB2(2064):S310 ERBB2(2064):S310Y

Genes: ERBB2(2064)

Variants: S310F G309A G309E S310 S310Y

[Paper-level Aggregated] PMCID: PMC6627713

Evidence Type(s): Oncogenic

Summary: Mutation: c.275_276insGGCC | Summary: The variant c.275_276insGGCC in TP53 is associated with tumor development or progression, contributing to oncogenic behavior.

Evidence Type: Oncogenic Mutation: c.837_838InsG | Summary: The variant c.837_838InsG in TP53 is implicated in tumor development or progression, indicating its oncogenic potential.

Evidence Type: Oncogenic Mutation: c.4467_4468insCATTTTG | Summary: The variant c.4467_4468insCATTTTG in APC is associated with tumor development or progression, suggesting it has oncogenic properties.

Evidence Type: Oncogenic Mutation: c.4098_4099delTCinsAT | Summary: The variant c.4098_4099delTCinsAT in APC contributes to tumor development or progression, indicating its role as an oncogenic variant.

Evidence Type: Oncogenic Mutation: c.589_590insGAGTT | Summary: The variant c.589_590insGAGTT in APC is linked to tumor development or progression, supporting its classification as an oncogenic variant.

Evidence Type: Oncogenic Mutation: c.183A>T; p.Gln61His | Summary: The KRAS variant (c.183A>T; p.Gln61His) was identified in tumor tissue, indicating its potential role in tumor development or progression.

Evidence Type: Oncogenic Mutation: c.169A>G; p.Lys57Glu | Summary: The variant c.169A>G is associated with a gain of function in the MEK1 protein, indicating its contribution to tumor development or progression.

Evidence Type: Oncogenic Mutation: c.638_639insA | Summary: The insertion mutation in NF1 leads to a premature stop codon, contributing to tumor development through loss of function and increased activation of the RAS signaling pathway.

Evidence Type: Oncogenic Mutation: c.5101A>T | Summary: The SNV in NF1 results in a premature stop codon, which is associated with tumor progression due to loss of function and enhanced RAS signaling.

Evidence Type: Oncogenic Mutation: c.1513C>T (p.Arg505Cys) | Summary: The c.1513C>T variant has been reported in several cancer types and is associated with loss of function of the protein, suggesting both oncogenic potential and functional impact.

Evidence Type: Oncogenic Mutation: c.1268G>T; p.Gly423Val | Summary: The presence of the FBXW7 variant c.1268G>T; p.Gly423Val suggests a role in tumor development or progression, supporting its classification as oncogenic.

Evidence Type: Oncogenic Mutation: c.199G>A | Summary: The c.199G>A variant contributes to tumor development or progression as it is associated with acquired resistance to anti-EGFR MoAbs.

Evidence Type: Oncogenic Mutation: c.169A>G | Summary: The c.169A>G variant contributes to tumor development or progression as it is associated with acquired resistance to anti-EGFR MoAbs.

Gene→Variant (gene-first): TP53(7157):c.275_276insGGCC APC(324):c.837_838InsG APC(324):c.4467_4468insCATTTTG APC(324):c.4098_4099delTCinsAT APC(324):c.589_590insGAGTT KRAS(3845):c.183A>T KRAS(3845):p.Gln61His MAP2K1(5604):c.169A>G MAP2K1(5604):p.Lys57Glu NF1(4763):c.638_639insA NF1(4763):c.5101A>T NA:c.1513C>T (p.Arg505Cys) FBXW7(55294):c.1268G>T FBXW7(55294):p.Gly423Val MAP2K1(5604):c.199G>A

Genes: TP53(7157) APC(324) KRAS(3845) MAP2K1(5604) NF1(4763) NA FBXW7(55294)

Variants: c.275_276insGGCC c.837_838InsG c.4467_4468insCATTTTG c.4098_4099delTCinsAT c.589_590insGAGTT c.183A>T p.Gln61His c.169A>G p.Lys57Glu c.638_639insA c.5101A>T c.1513C>T (p.Arg505Cys) c.1268G>T p.Gly423Val c.199G>A

[Paper-level Aggregated] PMCID: PMC6594036

Evidence Type(s): Oncogenic

Summary: Mutation: 2690A > G | Summary: The mutation 2690A > G in the TEK gene is associated with tumor development or progression.

Evidence Type: Oncogenic Mutation: c.2752A > G | Summary: The mutation c.2752A > G in the TEK gene is associated with tumor development or progression.

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

Genes: TEK(7010)

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

[Paper-level Aggregated] PMCID: PMC6549573

Evidence Type(s): Oncogenic

Summary: Mutation: G12D | Summary: The KRAS G12D mutation contributes to tumor development and progression in non-small-cell lung cancer (NSCLC) models and is associated with lung adenocarcinoma, particularly in patients with stage IV disease. It is implicated in the development of lung cancers and supports its classification as an oncogenic variant.

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

Genes: KRAS(3845)

Variants: G12D

[Paragraph-level] PMCID: PMC6549573 Section: RESULTS PassageIndex: 12

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: G12D | Summary: The KRAS G12D mutation is identified as contributing to tumor development or progression, particularly in the context of patients with KRAS G12D-mutant disease.

Gene→Variant (gene-first): 3845:G12D

Genes: 3845

Variants: G12D

[Paragraph-level] PMCID: PMC6549573 Section: RESULTS PassageIndex: 11

Evidence Type(s): Prognostic, Oncogenic

Summary: Evidence Type: Prognostic | Mutation: G12D | Summary: The KRAS G12D mutation is associated with prolonged survival in models with p53 deficiency, indicating a correlation with disease outcome independent of therapy. Evidence Type: Oncogenic | Mutation: G12D | Summary: The KRAS G12D mutation contributes to tumor development or progression, as evidenced by its presence in tumor models.

Gene→Variant (gene-first): 3845:G12D

Genes: 3845

Variants: G12D

[Paragraph-level] PMCID: PMC6549573 Section: RESULTS PassageIndex: 8

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: G12D | Summary: The KRAS G12D mutation was associated with a lack of response to bortezomib in the majority of patients, indicating its potential predictive value regarding therapy response. Evidence Type: Oncogenic | Mutation: G12D | Summary: The KRAS G12D mutation is implicated in the development and progression of lung adenocarcinoma, supporting its classification as an oncogenic variant.

Gene→Variant (gene-first): 3845:G12D

Genes: 3845

Variants: G12D

[Paragraph-level] PMCID: PMC6549573 Section: RESULTS PassageIndex: 4

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: G12D | Summary: The KRAS G12D mutation is associated with response evaluation to bortezomib therapy in lung cancer patients, indicating its potential predictive value for treatment response. Evidence Type: Oncogenic | Mutation: G12D | Summary: The KRAS G12D mutation is implicated in the development of lung cancers, supporting its classification as an oncogenic variant.

Gene→Variant (gene-first): 3845:G12D

Genes: 3845

Variants: G12D

[Paragraph-level] PMCID: PMC6549573 Section: RESULTS PassageIndex: 3

Evidence Type(s): Oncogenic, Predictive

Summary: Evidence Type: Oncogenic | Mutation: G12D | Summary: The KRAS G12D mutation is associated with lung adenocarcinoma and contributes to tumor development in patients with stage IV disease. Evidence Type: Predictive | Mutation: G12D | Summary: The presence of the KRAS G12D mutation in patients with lung cancer may correlate with response to treatment with bortezomib, indicating its predictive value for therapy outcomes.

Gene→Variant (gene-first): 3845:G12D

Genes: 3845

Variants: G12D

[Paper-level Aggregated] PMCID: PMC6547725

Evidence Type(s): Oncogenic

Summary: Mutation: p.G12A | Summary: The p.G12A mutation is described as affecting a classical position in the P-loop of KRAS, indicating its contribution to tumor development or progression.

Evidence Type: Oncogenic Mutation: p.G13H | Summary: The p.G13H mutation is noted to affect a classical position in the P-loop of KRAS, suggesting its role in tumor development or progression.

Evidence Type: Oncogenic Mutation: p.Q61L | Summary: The p.Q61L mutation is described as a classic pathogenic missense mutation, suggesting its contribution to tumor development or progression.

Evidence Type: Oncogenic Mutation: p.G12V | Summary: The p.G12V variant is classified as a classical oncogenic variant, indicating its role in tumor development or progression. It alters the intrinsic dissociation rate of the nucleotide and enhances signaling capabilities, as evidenced by increased levels of phosphorylated ERK and AKT in transfected cells.

Evidence Type: Oncogenic Mutation: Gln61 | Summary: The mention of insertions in tumor samples at Gln61 suggests that these variants contribute to tumor development or progression, classifying them as oncogenic.

Gene→Variant (gene-first): KRAS(3845):p.G12A KRAS(3845):p.G13H NRAS(4893):p.Q61L KRAS(3845):p.G12V RASA1(5921):Gln61

Genes: KRAS(3845) NRAS(4893) RASA1(5921)

Variants: p.G12A p.G13H p.Q61L p.G12V Gln61

[Paper-level Aggregated] PMCID: PMC6547681

Evidence Type(s): Oncogenic

Summary: Mutation: G101V | Summary: The G101V mutation in BCL-2 contributes to tumor progression by conferring resistance to therapy and altering drug binding characteristics, which may influence tumor development or progression.

Gene→Variant (gene-first): BCL2(596):G101V

Genes: BCL2(596)

Variants: G101V

[Paper-level Aggregated] PMCID: PMC6478919

Evidence Type(s): Oncogenic

Summary: Mutation: + 21 T > C | Summary: The transition from C to T at location 21 of BCL2 contributes to tumor development or progression by leading to increased BCL2 protein levels, which are associated with resistance to paclitaxel treatment in ovarian cancer patients.

Gene→Variant (gene-first): BCL2(596):+ 21 T > C

Genes: BCL2(596)

Variants: + 21 T > C

[Paper-level Aggregated] PMCID: PMC6368247

Evidence Type(s): Oncogenic

Summary: Mutation: Y537S | Summary: The Y537S mutation in ESR1 is associated with the emergence of new driver mutations during treatment and contributes to tumor development or progression, as it is positively selected during treatment.

Evidence Type: Oncogenic Mutation: p.Q257X | Summary: The p.Q257X mutation in RB1 is associated with resistance to treatment and the development of resistance to palbociclib and fulvestrant, indicating its role in tumor progression.

Evidence Type: Oncogenic Mutation: p.N519fs | Summary: The p.N519fs mutation in RB1 is linked to the emergence of a resistant subclone, suggesting its contribution to tumor development or progression.

Evidence Type: Oncogenic Mutation: p.K569E | Summary: The p.K569E mutation in FGFR2 is described as an activating mutation that contributes to tumor development, particularly in the context of resistance to treatment with palbociclib plus fulvestrant.

Evidence Type: Oncogenic Mutation: D538G | Summary: The D538G mutation in ESR1 was negatively selected during treatment, indicating its role in tumor progression and response to therapy, thus supporting its oncogenic potential.

Evidence Type: Oncogenic Mutation: E542K | Summary: The E542K mutation shows limited evidence for positive selection, indicating its potential role in tumor development or progression.

Evidence Type: Oncogenic Mutation: E545K | Summary: The E545K mutation is one of the most common acquired variants, suggesting its contribution to tumor development or progression.

Evidence Type: Oncogenic Mutation: H1047L | Summary: The H1047L mutation is validated as an acquired variant, indicating its potential role in tumor development or progression.

Evidence Type: Oncogenic Mutation: H1047R | Summary: The H1047R mutation is validated as an acquired variant, indicating its potential role in tumor development or progression.

Gene→Variant (gene-first): PTEN(5728):Y537S RB1(5925):p.Q257X RB1(5925):p.N519fs FGFR2(2263):p.K569E FGFR2(2263):D538G PIK3CA(5290):E542K PIK3CA(5290):E545K PIK3CA(5290):H1047L PIK3CA(5290):H1047R

Genes: PTEN(5728) RB1(5925) FGFR2(2263) PIK3CA(5290)

Variants: Y537S p.Q257X p.N519fs p.K569E D538G E542K E545K H1047L H1047R

[Paper-level Aggregated] PMCID: PMC6333965

Evidence Type(s): Oncogenic

Summary: Mutation: E545K | Summary: The PIK3CA E545K mutation is noted as a potentially targetable alteration and is established as a canonical mutation contributing to tumor development.

Evidence Type: Oncogenic Mutation: R58X | Summary: The CDKN2A R58X mutation is mentioned as a potentially targetable alteration and is associated with tumor development due to its role in cell cycle regulation.

Evidence Type: Oncogenic Mutation: R209Q/W | Summary: The TP53 inactivating mutations R209Q/W are implicated in cell cycle deregulation, contributing to tumor progression.

Evidence Type: Oncogenic Mutation: R243W/Q | Summary: The TP53 inactivating mutations R243W/Q are associated with cell cycle deregulation, indicating their role in tumor development.

Gene→Variant (gene-first): PIK3CA(5290):E545K CDKN2A(1029):R58X TP53(7157):R209Q/W TP53(7157):R243W/Q

Genes: PIK3CA(5290) CDKN2A(1029) TP53(7157)

Variants: E545K R58X R209Q/W R243W/Q

[Paper-level Aggregated] PMCID: PMC6173734

Evidence Type(s): Oncogenic

Summary: Mutation: c.422G>A; p.Cys141Tyr | Summary: The TP53 missense variant c.422G>A (p.Cys141Tyr) is described as pathogenic and contributes to tumor development or progression, indicating its oncogenic potential.

Gene→Variant (gene-first): TP53(7157):c.422G>A TP53(7157):p.Cys141Tyr

Genes: TP53(7157)

Variants: c.422G>A p.Cys141Tyr

[Paragraph-level] PMCID: PMC6173734 Section: RESULTS PassageIndex: 2

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: c.422G>A; p.Cys141Tyr | Summary: The TP53 missense variant c.422G>A (p.Cys141Tyr) is described as pathogenic and contributes to tumor development or progression, indicating its oncogenic potential.

Gene→Variant (gene-first): 7157:c.422G>A 7157:p.Cys141Tyr

Genes: 7157

Variants: c.422G>A p.Cys141Tyr

[Paper-level Aggregated] PMCID: PMC5873857

Evidence Type(s): Oncogenic

Summary: Mutation: c.159_173del | Summary: The variant c.159_173del is part of a cluster of pathogenic variants identified in MAP2K1, contributing to the development of arteriovenous malformations (AVMs) and indicating its role in tumor progression within the RAS/MAPK signaling pathway.

Evidence Type: Oncogenic Mutation: BRAFV600E | Summary: The BRAFV600E mutation contributes to tumor development by leading to disordered vessel formation and impaired blood flow in zebrafish models, recapitulating clinical features of vascular malformations.

Gene→Variant (gene-first): MAP2K1(5604):c.159_173del BRAF(673):BRAFV600E

Genes: MAP2K1(5604) BRAF(673)

Variants: c.159_173del BRAFV600E

[Paper-level Aggregated] PMCID: PMC5822176

Evidence Type(s): Oncogenic

Summary: Mutation: K27M | Summary: The H3 K27M mutation contributes to tumor development and progression, as it is implicated in various types of gliomas, including pediatric diffuse intrinsic pontine gliomas and adult midline diffuse gliomas. It is associated with the transformation of low-grade gliomas to glioblastoma and a lower frequency of ATRX mutation/loss in tumors, indicating its significant role in tumorigenesis.

Gene→Variant (gene-first): IDH1(3417):K27M

Genes: IDH1(3417)

Variants: K27M

[Paper-level Aggregated] PMCID: PMC5820258

Evidence Type(s): Oncogenic

Summary: Mutation: p.K601E | Summary: The BRAF p.K601E mutation is described as oncogenic and contributes to tumor development and progression, making it a target for therapies such as MEK inhibitors. It was retained in the subclone that emerged during venetoclax therapy.

Evidence Type: Oncogenic Mutation: p.Q36H | Summary: The BTG1 missense mutation p.Q36H may contribute to tumor development or progression in CLL cells under targeted BCL2-inhibition, providing a survival advantage. It is part of a branch observed only in the relapse sample, suggesting its contribution to tumor evolution and progression.

Evidence Type: Oncogenic Mutation: p.E46K | Summary: The p.E46K mutation in BTG1 contributes to tumor evolution and is selected as a dominant clone, indicating its role in tumor progression. It may also contribute to tumor development or progression in CLL cells under targeted BCL2-inhibition.

Evidence Type: Oncogenic Mutation: p.S321fs | Summary: The mutation p.S321fs in MLL3 is implicated in tumor development, as it was present in the subclone that persisted through treatment.

Evidence Type: Oncogenic Mutation: p.Q547fs | Summary: The frameshift deletion p.Q547fs in BIRC3 is recognized as a driver mutation in CLL, contributing to tumorigenesis.

Evidence Type: Oncogenic Mutation: c.1996A > C | Summary: The SF3B1 mutation c.1996A > C was identified in cancer cell subclones that evolved during venetoclax exposure, indicating its contribution to tumor development and progression.

Evidence Type: Oncogenic Mutation: c.1997A > C | Summary: The SF3B1 mutation c.1997A > C was found in subclones that emerged during treatment with venetoclax, suggesting its role in tumor development and progression.

Evidence Type: Oncogenic Mutation: p.K666Q | Summary: The mutation p.K666Q was detected in small subclones before treatment and evolved during venetoclax therapy, indicating its involvement in oncogenic processes.

Evidence Type: Oncogenic Mutation: p.K666T | Summary: The mutation p.K666T was present in subclones that evolved during venetoclax exposure, supporting its role in tumor development and progression.

Evidence Type: Oncogenic Mutation: BRAFV600E | Summary: The BRAFV600E mutation contributes to tumor development and progression, as evidenced by its role in inducing venetoclax resistance in cell lines.

Gene→Variant (gene-first): BRAF(673):p.K601E BTG1(694):p.Q36H TP53(7157):p.E46K KMT2C(58508):p.S321fs BIRC3(330):p.Q547fs SF3B1(23451):c.1996A > C SF3B1(23451):c.1997A > C SF3B1(23451):p.K666Q SF3B1(23451):p.K666T BRAF(673):BRAFV600E

Genes: BRAF(673) BTG1(694) TP53(7157) KMT2C(58508) BIRC3(330) SF3B1(23451)

Variants: p.K601E p.Q36H p.E46K p.S321fs p.Q547fs c.1996A > C c.1997A > C p.K666Q p.K666T BRAFV600E

[Paper-level Aggregated] PMCID: PMC5792548

Evidence Type(s): Oncogenic

Summary: Mutation: T790M | Summary: The EGFR T790M mutation contributes to tumor development and progression, as it is implicated in acquired resistance to EGFR tyrosine kinase inhibitors and is maintained in osimertinib-resistant cells. It is also associated with gefitinib resistance in lung adenocarcinoma.

Evidence Type: Oncogenic Mutation: 19del | Summary: The EGFR exon 19 deletion (19del) is associated with tumor development and progression in lung cancer, as indicated by its presence in both naive and acquired gefitinib-resistant cell lines. It is also linked to gefitinib resistance in lung adenocarcinoma.

Evidence Type: Oncogenic Mutation: C797S | Summary: The C797S mutation contributes to tumor progression by conferring resistance to EGFR-TKIs, which is a characteristic of oncogenic behavior.

Gene→Variant (gene-first): EGFR(1956):T790M EGFR(1956):19del EGFR(1956):C797S

Genes: EGFR(1956)

Variants: T790M 19del C797S

[Paper-level Aggregated] PMCID: PMC5762309

Evidence Type(s): Oncogenic

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

Evidence Type: Oncogenic Mutation: L576P | Summary: The L576P mutation is mentioned as a primary mutant in the context of selective inhibition, indicating its role in tumor progression.

Evidence Type: Oncogenic Mutation: T670I | Summary: The T670I mutation is classified as a secondary mutant, contributing to tumor development in the context of selective inhibition.

Evidence Type: Oncogenic Mutation: V654A | Summary: The V654A mutation is noted as a secondary mutant involved in tumor progression, as indicated by its context in selective inhibition.

Evidence Type: Oncogenic Mutation: N822K | Summary: The N822K mutation is mentioned in the context of activation loop mutations, suggesting its contribution to tumor development.

Evidence Type: Oncogenic Mutation: D816V | Summary: The D816V mutation is described as an activation loop mutation, indicating its role in tumor progression.

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

Genes: KIT(3815)

Variants: V559D L576P T670I V654A N822K D816V

[Paper-level Aggregated] PMCID: PMC5652823

Evidence Type(s): Oncogenic

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

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

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

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

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

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

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

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

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

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

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

[Paper-level Aggregated] PMCID: PMC5629366

Evidence Type(s): Oncogenic

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

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

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

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

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

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

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

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

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

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

[Paragraph-level] PMCID: PMC5629366 Section: RESULTS PassageIndex: 18

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: R132H | Summary: The R132H mutation in IDH1 is associated with treatment response to BAY1436032, indicating a correlation with sensitivity to this specific therapy. Evidence Type: Oncogenic | Mutation: R132H | Summary: The R132H mutation contributes to tumor development or progression in human AML cells, as indicated by its presence in the context of IDH1/IDH2 mutations.

Gene→Variant (gene-first): 3417:R132H

Genes: 3417

Variants: R132H

[Paper-level Aggregated] PMCID: PMC5615879

Evidence Type(s): Oncogenic

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Genes: KIT(3815) POTEF(728378)

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

[Paragraph-level] PMCID: PMC5615879 Section: ABSTRACT PassageIndex: 6

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: c.1666C>G | Summary: The mutation p.Q556E (c.1666C>G) is associated with tumor development or progression as part of the KIT mutations observed in the study. Evidence Type: Oncogenic | Mutation: c.1666_1668dupCAG | Summary: The mutation p.Q556dup (c.1666_1668dupCAG) contributes to tumor development or progression, as it is one of the common KIT mutations identified. Evidence Type: Oncogenic | Mutation: c.1672_1677delAAGGTTinsAGT | Summary: The mutation p.K558_V559delinsS (c.1672_1677delAAGGTTinsAGT) is implicated in tumor development or progression, being part of the KIT mutations found in the cases. Evidence Type: Oncogenic | Mutation: c.1509_1510insACCTAT | Summary: The mutation p.Y503_F504insTY (c.1509_1510insACCTAT) is associated with tumor development or progression, as it is one of the identified KIT mutations. Evidence Type: Oncogenic | Mutation: c.1925A>G | Summary: The mutation p.K642R (c.1925A>G) is linked to tumor development or progression, as it is part of the KIT mutations observed in the study.

Gene→Variant (gene-first): 3815:Ala-Tyr 3815:c.1509_1510insACCTAT 728378:c.1666C>G 3815:c.1666_1668dupCAG 3815:c.1672_1677delAAGGTTinsAGT 5156:c.1925A>G 3815:p.K558_V559delinsS 728378:p.K642R 728378:p.Q556E 3815:p.Q556dup 3815:p.Y503_F504insTY

Genes: 3815 728378 5156

Variants: Ala-Tyr c.1509_1510insACCTAT c.1666C>G c.1666_1668dupCAG c.1672_1677delAAGGTTinsAGT c.1925A>G p.K558_V559delinsS p.K642R p.Q556E p.Q556dup p.Y503_F504insTY

[Paper-level Aggregated] PMCID: PMC5509015

Evidence Type(s): Oncogenic

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

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

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

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

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

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

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

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

Genes: VHL(7428)

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

[Paper-level Aggregated] PMCID: PMC5481739

Evidence Type(s): Oncogenic

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

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

Genes: DNMT3A(1788)

Variants: V716F

[Paper-level Aggregated] PMCID: PMC5355930

Evidence Type(s): Oncogenic

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

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

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

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

Genes: PIK3CA(5290)

Variants: H1047R E545K E542K

[Paper-level Aggregated] PMCID: PMC5122709

Evidence Type(s): Oncogenic

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

Evidence Type: Oncogenic Mutation: BRAFV600E | Summary: The BRAFV600E mutation contributes to tumor development in metastatic melanoma, supporting its classification as an oncogenic variant.

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

Genes: BRAF(673) NA

Variants: V600E BRAFV600E

[Paper-level Aggregated] PMCID: PMC5111006

Evidence Type(s): Oncogenic

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

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

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

Genes: EGFR(1956) CHEK2(11200)

Variants: L858R p.R474C

[Paper-level Aggregated] PMCID: PMC5029699

Evidence Type(s): Oncogenic

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

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

Evidence Type: Oncogenic Mutation: N540 | Summary: The N540 mutation in FGFR3 contributes to tumor development and is noted in the context of cancer.

Evidence Type: Oncogenic Mutation: N540K | Summary: The N540K mutation is frequently observed in cancer, linked to a transformed phenotype and anchorage independent growth in cell lines, indicating its contribution to tumor progression.

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

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

Evidence Type: Oncogenic Mutation: R675G | Summary: The R675G variant in FGFR1 KD shows higher activity compared to wild type, indicating its potential role in tumor development or progression.

Evidence Type: Oncogenic Mutation: V555M | Summary: The V555M mutation in FGFR3 is described as a gatekeeper mutation that reduces drug binding, indicating its role in tumor development or progression.

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

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

Genes: FGFR3(2261) FGFR1(2260)

Variants: K650 G697 N540 N540K R669 K650E R675G V555M R669G

[Paper-level Aggregated] PMCID: PMC5019182

Evidence Type(s): Oncogenic

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Genes: PIK3CA(5290) TSC2(7249)

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