[Paper-level Aggregated] PMCID: PMC11551396

Evidence Type(s): Predictive

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

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

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

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

Genes: EGFR(1956)

Variants: L858R N771insSVD T790M

[Paper-level Aggregated] PMCID: PMC11272140

Evidence Type(s): Predictive

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

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

Genes: ROS1(6098)

Variants: G2032R

[Paper-level Aggregated] PMCID: PMC11253285

Evidence Type(s): Predictive

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

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

Genes: PARP1(142)

Variants: S4D

[Paper-level Aggregated] PMCID: PMC10690049

Evidence Type(s): Predictive

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

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

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

Genes: KRAS(3845)

Variants: G12C G12D

[Paper-level Aggregated] PMCID: PMC10618648

Evidence Type(s): Predictive

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

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

Genes: ERBB2(2064)

Variants: T733I

[Paper-level Aggregated] PMCID: PMC10527017

Evidence Type(s): Predictive

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

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

Genes: ERBB2(2064)

Variants: V777L

[Paragraph-level] PMCID: PMC10527017 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Oncogenic, Predictive, Functional

Summary: Evidence Type: Oncogenic | Mutation: V777L | Summary: The HER2V777L mutation contributes to tumor development and progression in breast cancer, as evidenced by accelerated tumor formation and increased invasion in genetically engineered mice. Evidence Type: Predictive | Mutation: V777L | Summary: The HER2V777L mutation is associated with resistance to the pan-HER tyrosine kinase inhibitor neratinib, indicating its predictive value for therapy response. Evidence Type: Functional | Mutation: V777L | Summary: The HER2V777L mutation alters molecular function, as indicated by changes in gene expression and cell cycle markers in breast cancer organoids.

Gene→Variant (gene-first): 2064:V777L

Genes: 2064

Variants: V777L

[Paper-level Aggregated] PMCID: PMC10524391

Evidence Type(s): Predictive

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

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

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

Genes: EGFR(1956)

Variants: T790M C797S

[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: 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

[Paper-level Aggregated] PMCID: PMC10390864

Evidence Type(s): Predictive

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

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

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

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

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

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

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

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

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

Genes: RAD51C(5889)

Variants: E94K G306R G130R K131I T132R Q133E G302V L138F

[Paragraph-level] PMCID: PMC10390864 Section: RESULTS PassageIndex: 10

Evidence Type(s): Functional, Predictive

Summary: Evidence Type: Functional | Mutation: L138F | Summary: The L138F variant is characterized as deleterious and shows reduced HDR activity in U2OS cells, indicating that it alters molecular function related to homologous recombination. Evidence Type: Predictive | Mutation: L138F | Summary: The L138F variant is associated with sensitivity to cisplatin and olaparib in CL-V4B cells, suggesting it may correlate with response to specific therapies.

Gene→Variant (gene-first): 5889:L138F

Genes: 5889

Variants: L138F

[Paragraph-level] PMCID: PMC10390864 Section: RESULTS PassageIndex: 9

Evidence Type(s): Functional, Predictive

Summary: Evidence Type: Functional | Mutation: G130R | Summary: The G130R variant was confirmed to have functional effects in a human cell line, indicating it alters molecular or biochemical function. Evidence Type: Functional | Mutation: K131I | Summary: The K131I variant was confirmed to have functional effects in a human cell line, indicating it alters molecular or biochemical function. Evidence Type: Functional | Mutation: T132R | Summary: The T132R variant was confirmed to have functional effects in a human cell line, indicating it alters molecular or biochemical function. Evidence Type: Functional | Mutation: Q133E | Summary: The Q133E variant was confirmed to have functional effects in a human cell line, indicating it alters molecular or biochemical function. Evidence Type: Functional | Mutation: L138F | Summary: The L138F variant was confirmed to have functional effects in a human cell line, indicating it alters molecular or biochemical function. Evidence Type: Functional | Mutation: R168G | Summary: The R168G variant was confirmed to have functional effects in a human cell line, indicating it alters molecular or biochemical function. Evidence Type: Functional | Mutation: G302V | Summary: The G302V variant was confirmed to have functional effects in a human cell line, indicating it alters molecular or biochemical function. Evidence Type: Predictive | Mutation: G130R | Summary: The G130R variant showed sensitivity to olaparib compared with WT-complemented cells, indicating a correlation with response to therapy. Evidence Type: Predictive | Mutation: K131I | Summary: The K131I variant showed sensitivity to olaparib compared with WT-complemented cells, indicating a correlation with response to therapy. Evidence Type: Predictive | Mutation: T132R | Summary: The T132R variant showed sensitivity to olaparib compared with WT-complemented cells, indicating a correlation with response to therapy. Evidence Type: Predictive | Mutation: Q133E | Summary: The Q133E variant had intermediate effects on sensitivity to olaparib compared with WT-complemented cells, indicating a correlation with response to therapy. Evidence Type: Predictive | Mutation: G302V | Summary: The G302V variant had intermediate effects on sensitivity to olaparib compared with WT-complemented cells, indicating a correlation with response to therapy.

Gene→Variant (gene-first): 5889:G130R 5889:G302V 5889:K131I 5889:L138F 5889:Q133E 5889:R168G 5889:T132R

Genes: 5889

Variants: G130R G302V K131I L138F Q133E R168G T132R

[Paragraph-level] PMCID: PMC10390864 Section: RESULTS PassageIndex: 5

Evidence Type(s): Predictive, Functional

Summary: Evidence Type: Predictive | Mutation: E94K | Summary: The variant p.Glu94Lys (E94K) shows a significant reduction in sensitivity to cisplatin and a notable decrease in sensitivity to olaparib, indicating its potential role in predicting treatment response. Evidence Type: Predictive | Mutation: G306R | Summary: The variant p.Gly306Arg (G306R) demonstrates a marked reduction in sensitivity to both cisplatin and olaparib, suggesting its predictive value for treatment response. Evidence Type: Functional | Mutation: E94K | Summary: The variant p.Glu94Lys (E94K) is associated with altered IC50 values for cisplatin and olaparib, indicating a change in molecular function. Evidence Type: Functional | Mutation: G306R | Summary: The variant p.Gly306Arg (G306R) exhibits altered IC50 values for cisplatin and olaparib, suggesting a functional impact on drug response.

Gene→Variant (gene-first): 5889:E94K 5889:G306R 5889:p.Glu94Lys 5889:p.Gly306Arg

Genes: 5889

Variants: E94K G306R p.Glu94Lys p.Gly306Arg

[Paper-level Aggregated] PMCID: PMC10283448

Evidence Type(s): Predictive

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

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

Genes: ROS1(6098)

Variants: G2032R

[Paragraph-level] PMCID: PMC10283448 Section: RESULTS PassageIndex: 12

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: G2032R | Summary: The G2032R mutation is associated with a positive response to repotrectinib treatment in a patient with ROS1-rearranged NSCLC, indicating its predictive value for therapy response. Evidence Type: Oncogenic | Mutation: G2032R | Summary: The G2032R mutation is part of the CD74-ROS1 rearrangement, which contributes to tumor development in the context of ROS1-rearranged non-small cell lung cancer (NSCLC).

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

Genes: 6098

Variants: G2032R

[Paragraph-level] PMCID: PMC10283448 Section: RESULTS PassageIndex: 10

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: G2032R | Summary: The ROS1-G2032R mutation is associated with varying responses to different tyrosine kinase inhibitors (TKIs), indicating its predictive value for treatment outcomes with cabozantinib and lorlatinib. Evidence Type: Oncogenic | Mutation: G2032R | Summary: The ROS1-G2032R mutation contributes to tumor growth in the YU1079 model, demonstrating its role in oncogenic processes.

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

Genes: 6098

Variants: G2032R

[Paragraph-level] PMCID: PMC10283448 Section: RESULTS PassageIndex: 9

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: G2032R | Summary: The G2032R mutation is associated with resistance to crizotinib, and the passage indicates that repotrectinib can overcome this resistance, suggesting a predictive relationship with therapy response. Evidence Type: Oncogenic | Mutation: G2032R | Summary: The G2032R mutation in ROS1 is implicated in crizotinib resistance, indicating its role in tumor development or progression, thus supporting its classification as oncogenic.

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

Genes: 6098

Variants: G2032R

[Paper-level Aggregated] PMCID: PMC10183391

Evidence Type(s): Predictive

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

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

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

Genes: ERBB2(2064)

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

[Paragraph-level] PMCID: PMC10183391 Section: ABSTRACT PassageIndex: 6

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: p.L755P | Summary: The p.L755P mutation in HER2 is associated with a response to osimertinib in a patient with NSCLC, suggesting its potential as a predictive biomarker for targeted treatment. Evidence Type: Oncogenic | Mutation: p.L755P | Summary: The p.L755P mutation contributes to tumor development or progression in the context of NSCLC, indicating its oncogenic potential.

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

Genes: 2064

Variants: p.L755P

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

Evidence Type(s): Oncogenic, Predictive

Summary: Evidence Type: Oncogenic | Mutation: c.2262_2264delinsTCC | Summary: The ERBB2 exon 19 mutation is associated with tumor development or progression in the context of stage IV NSCLC. Evidence Type: Predictive | Mutation: c.2262_2264delinsTCC | Summary: The mutation correlates with the patient's response to osimertinib treatment, indicating its predictive value for therapy sensitivity. Evidence Type: Oncogenic | Mutation: p.(L755P) | Summary: The p.(L755P) mutation in ERBB2 is implicated in contributing to tumor development or progression in NSCLC. Evidence Type: Predictive | Mutation: p.(L755P) | Summary: This mutation is associated with the patient's response to osimertinib, suggesting its predictive role in therapy sensitivity.

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

Genes: 2064

Variants: c.2262_2264delinsTCC p.(L755P)

[Paper-level Aggregated] PMCID: PMC10082285

Evidence Type(s): Predictive

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

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

Genes: EGFR(1956)

Variants: L858R

[Paragraph-level] PMCID: PMC10082285 Section: ABSTRACT PassageIndex: 5

Evidence Type(s): Predictive, Diagnostic

Summary: Evidence Type: Predictive | Mutation: L858R | Summary: The L858R mutation is associated with response to osimertinib therapy in patients with EGFR-mutated NSCLC, indicating its predictive value for treatment sensitivity. Evidence Type: Diagnostic | Mutation: L858R | Summary: The presence of the L858R mutation is used to classify and confirm the diagnosis of EGFR-mutated NSCLC, supporting its role as a diagnostic marker.

Gene→Variant (gene-first): 1956:L858R

Genes: 1956

Variants: L858R

[Paper-level Aggregated] PMCID: PMC10011885

Evidence Type(s): Predictive

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

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

Genes: BRAF(673)

Variants: V600E

[Paragraph-level] PMCID: PMC10011885 Section: ABSTRACT PassageIndex: 7

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: V600E | Summary: The BRAF V600E mutation in metastatic colorectal cancer is associated with treatment response to vemurafenib and erlotinib, indicating its predictive value for therapy efficacy. Evidence Type: Oncogenic | Mutation: V600E | Summary: The BRAF V600E mutation is implicated in tumor development and progression in metastatic colorectal cancer, supporting its classification as an oncogenic variant.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

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

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: V600E | Summary: The BRAF V600E mutation is associated with the development of combination therapies involving oral BRAF inhibitors and EGFR-targeting antibodies, indicating its potential role in predicting response to these therapies. Evidence Type: Oncogenic | Mutation: V600E | Summary: The BRAF V600E mutation is implicated in the progression of metastatic colorectal cancer, suggesting its role as an oncogenic driver in tumor development.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paper-level Aggregated] PMCID: PMC9900321

Evidence Type(s): Predictive

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

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

Genes: KRAS(3845)

Variants: Gly-to-Asp

[Paper-level Aggregated] PMCID: PMC9859631

Evidence Type(s): Predictive

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

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

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

Genes: ERBB2(2064) EGFR(1956)

Variants: c.1899-2A>G L858R

[Paragraph-level] PMCID: PMC9859631 Section: RESULTS PassageIndex: 11

Evidence Type(s): Predictive, Oncogenic

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

Gene→Variant (gene-first): 2064:D769Y 2064:L755S 1956:L858R 2064:c.1899-32_1909del

Genes: 2064 1956

Variants: D769Y L755S L858R c.1899-32_1909del

[Paragraph-level] PMCID: PMC9859631 Section: RESULTS PassageIndex: 5

Evidence Type(s): Oncogenic, Predictive

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

Gene→Variant (gene-first): 2064:c.1899-2A>G 2064:c.1899-880_1946+761del

Genes: 2064

Variants: c.1899-2A>G c.1899-880_1946+761del

[Paper-level Aggregated] PMCID: PMC9441062

Evidence Type(s): Predictive

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

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

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

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

Genes: EGFR(1956)

Variants: T790M C797S/G L718V/Q

[Paper-level Aggregated] PMCID: PMC9398166

Evidence Type(s): Predictive

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Genes: ALK(238)

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

[Paper-level Aggregated] PMCID: PMC9365372

Evidence Type(s): Predictive

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

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

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

Genes: EGFR(1956)

Variants: T790M Thr790Met

[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

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

Evidence Type(s): Predictive

Summary: Evidence Type: Predictive | Mutation: T790M | Summary: The T790M mutation is associated with resistance to prior EGFR inhibitors and is evaluated for its role in determining the efficacy of abivertinib in patients with non-small cell lung cancer. Evidence Type: Predictive | Mutation: Thr790Met | Summary: The Thr790Met mutation is linked to resistance against previous EGFR inhibitors and is being assessed for its impact on the response to abivertinib in non-small cell lung cancer patients.

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

Genes: 1956

Variants: T790M Thr790Met

[Paper-level Aggregated] PMCID: PMC9338780

Evidence Type(s): Predictive

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

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

Genes: BRAF(673)

Variants: V600E

[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

[Paper-level Aggregated] PMCID: PMC8887939

Evidence Type(s): Predictive

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

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

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

Genes: ERBB2(2064)

Variants: A775dupYVMA G776delinsVC

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

Evidence Type(s): Predictive

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

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

Genes: 2064

Variants: A775dupYVMA G776delinsVC

[Paper-level Aggregated] PMCID: PMC8727519

Evidence Type(s): Predictive

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

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

Genes: EGFR(1956)

Variants: T790M

[Paper-level Aggregated] PMCID: PMC8700411

Evidence Type(s): Predictive

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

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

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

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

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

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

Genes: EGFR(1956)

Variants: D770_N771insSVD V769dupASV G770 D770 Y764insFQEA

[Paper-level Aggregated] PMCID: PMC8453302

Evidence Type(s): Predictive

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

Evidence Type: Predictive

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

Genes: ERBB2(2064)

Variants: G292R

[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): Predictive

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

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

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

Genes: EGFR(1956)

Variants: L858R T790M

[Paragraph-level] PMCID: PMC8307492 Section: RESULTS PassageIndex: 18

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: T790M | Summary: The T790M mutation is associated with resistance to EGFR inhibitors, specifically indicating a mechanism of resistance to the third-generation EGFR inhibitor osimertinib. 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. Evidence Type: Oncogenic | Mutation: L858R | Summary: The L858R mutation is known to contribute to tumor development or progression in the context of EGFR mutations. 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: L861Q | Summary: The L861Q mutation is part of a composite mutation that is implicated in tumor development or progression.

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

Genes: 1956

Variants: G719S L858R L861Q T790M

[Paragraph-level] PMCID: PMC8307492 Section: RESULTS PassageIndex: 16

Evidence Type(s): Predictive, Prognostic

Summary: Evidence Type: Predictive | Mutation: L858R | Summary: The L858R mutation correlates with response to first-line targeted therapy, as indicated by the proportion of patients receiving this therapy. Evidence Type: Prognostic | Mutation: L858R | Summary: The L858R mutation is associated with median overall survival (OS) outcomes, with a median OS of 18.3 months for patients treated with first-line targeted therapy.

Gene→Variant (gene-first): 1956:L858R

Genes: 1956

Variants: L858R

[Paper-level Aggregated] PMCID: PMC8285406

Evidence Type(s): Predictive

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[Paragraph-level] PMCID: PMC8285406 Section: RESULTS PassageIndex: 22

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: S249C | Summary: The S249C mutation in FGFR3 is associated with a partial or complete response to treatment with FGFR TKIs, indicating its correlation with drug efficacy. Evidence Type: Oncogenic | Mutation: S249C | Summary: The S249C mutation is identified as the most frequent mutation of FGFR3, suggesting its role in tumor development or progression.

Gene→Variant (gene-first): 2261:S249C

Genes: 2261

Variants: S249C

[Paragraph-level] PMCID: PMC8285406 Section: RESULTS PassageIndex: 20

Evidence Type(s): Oncogenic, Predictive

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

Gene→Variant (gene-first): 2261:K650E 2261:K650M 2261:S249C 2261:Y373C

Genes: 2261

Variants: K650E K650M S249C Y373C

[Paragraph-level] PMCID: PMC8285406 Section: RESULTS PassageIndex: 16

Evidence Type(s): Predictive

Summary: Evidence Type: Predictive | Mutation: N546K | Summary: The variant FGFR1 N546K was associated with a lack of effectiveness of E7090 and erdafitinib in suppressing tumor growth, indicating a potential resistance to these therapies. Evidence Type: Predictive | Mutation: N549K | Summary: Tumors with the FGFR2 N549K variant exhibited a better response to treatment with E7090 compared to erdafitinib, suggesting a correlation with therapy effectiveness. Evidence Type: Predictive | Mutation: R248C | Summary: The FGFR3 R248C variant showed significant antitumor activity against tumors treated with E7090, indicating a potential sensitivity to this therapy. Evidence Type: Predictive | Mutation: K650N | Summary: The FGFR3 K650N variant was associated with significantly decreased tumor volumes in response to both E7090 and erdafitinib, indicating a favorable response to these therapies. Evidence Type: Predictive | Mutation: K650M | Summary: The drug responses of tumors with the FGFR3 K650M variant were similar to those recorded in vitro, suggesting a correlation with therapy effectiveness.

Gene→Variant (gene-first): 2261:K650M 2261:K650N 2260:N546K 2263:N549K 2261:R248C

Genes: 2261 2260 2263

Variants: K650M K650N N546K N549K R248C

[Paragraph-level] PMCID: PMC8285406 Section: RESULTS PassageIndex: 14

Evidence Type(s): Predictive

Summary: Evidence Type: Predictive | Mutation: K650M | Summary: The K650M mutation in FGFR3 shows a correlation with response to the FGFR TKI E7090, indicating its predictive value for therapy response. Evidence Type: Predictive | Mutation: K650N | Summary: The K650N mutation in FGFR3 demonstrates decreased phosphorylation at lower concentrations of the FGFR TKI E7090, suggesting its predictive relevance for therapy response.

Gene→Variant (gene-first): 2261:K650M 2261:K650N

Genes: 2261

Variants: K650M K650N

[Paragraph-level] PMCID: PMC8285406 Section: RESULTS PassageIndex: 13

Evidence Type(s): Predictive

Summary: Evidence Type: Predictive | Mutation: G12V | Summary: The KRAS G12V variant is associated with resistance to all FGFR inhibitors, indicating its predictive role in therapy response. Evidence Type: Predictive | Mutation: N546K | Summary: The FGFR1 N546K variant is included in a cluster that is relatively resistant to all FGFR inhibitors, suggesting its predictive significance in treatment response. Evidence Type: Predictive | Mutation: N549D/K | Summary: The FGFR N549D/K variants are part of a cluster that shows resistance to all FGFR inhibitors, highlighting their predictive value in therapy response.

Gene→Variant (gene-first): 3845:G12V 2260:N546K 2263:N549D/K

Genes: 3845 2260 2263

Variants: G12V N546K N549D/K

[Paragraph-level] PMCID: PMC8285406 Section: RESULTS PassageIndex: 12

Evidence Type(s): Predictive

Summary: Evidence Type: Predictive | Mutation: N549D | Summary: The N549D variant in FGFR2 is associated with different drug sensitivities to FGFR inhibitors, indicating a correlation with treatment response. Evidence Type: Predictive | Mutation: N549H | Summary: The N549H variant in FGFR2 shows varying drug sensitivities to FGFR inhibitors, suggesting its role in influencing treatment response. Evidence Type: Predictive | Mutation: K656E | Summary: The K656E variant in FGFR3 is linked to different sensitivities to FGFR inhibitors, indicating its potential impact on treatment response. Evidence Type: Predictive | Mutation: K656M | Summary: The K656M variant in FGFR3 demonstrates varying drug sensitivities to FGFR inhibitors, suggesting its relevance in treatment response. Evidence Type: Predictive | Mutation: K656N | Summary: The K656N variant in FGFR3 is associated with different drug sensitivities to FGFR inhibitors, indicating its role in influencing treatment response.

Gene→Variant (gene-first): 2263:K656 2263:K656E/M 2263:N549 2263:N549D/H

Genes: 2263

Variants: K656 K656E/M N549 N549D/H

[Paragraph-level] PMCID: PMC8285406 Section: RESULTS PassageIndex: 11

Evidence Type(s): Predictive

Summary: Evidence Type: Predictive | Mutation: N546K | Summary: The N546K variant is associated with resistance to FGFR TKIs, indicating its role in predicting drug sensitivity. Evidence Type: Predictive | Mutation: N549D/K | Summary: The N549D/K variant shows relative resistance to FGFR TKIs, suggesting its predictive value for treatment response. Evidence Type: Predictive | Mutation: N535K | Summary: The N535K variant is sensitive to the FGFR4 inhibitor H3B-6527, indicating its predictive role in therapy response.

Gene→Variant (gene-first): 2264:N535K 2260:N546K 2263:N549D/K 2263:V550L

Genes: 2264 2260 2263

Variants: N535K N546K N549D/K V550L

[Paper-level Aggregated] PMCID: PMC8255005

Evidence Type(s): Predictive

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

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

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

Genes: FLT3(2322)

Variants: F691L F691

[Paragraph-level] PMCID: PMC8255005 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Prognostic, Predictive, Oncogenic

Summary: Evidence Type: Prognostic | Mutation: D835 | Summary: The D835 mutation is associated with poor prognosis in acute myeloid leukemia (AML). Evidence Type: Predictive | Mutation: F691L | Summary: The F691L mutation is described as a "gatekeeper" mutation that is resistant to most available FLT3 inhibitors, indicating its role in treatment resistance. Evidence Type: Oncogenic | Mutation: D835Y | Summary: The D835Y mutation is part of the FLT3-TKD mutations that contribute to tumor development and progression in AML. Evidence Type: Oncogenic | Mutation: F691 | Summary: The F691 mutation is implicated in the resistance to FLT3 inhibitors and contributes to tumor progression in AML.

Gene→Variant (gene-first): 2322:D835 2322:D835Y 2322:F691 2322:F691L

Genes: 2322

Variants: D835 D835Y F691 F691L

[Paper-level Aggregated] PMCID: PMC8203843

Evidence Type(s): Predictive

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

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

Genes: IDH1(3417)

Variants: R132H

[Paragraph-level] PMCID: PMC8203843 Section: RESULTS PassageIndex: 11

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: R132H | Summary: The IDH1 R132H mutation is associated with sensitivity to PARP inhibitors, indicating a correlation with treatment response. Evidence Type: Oncogenic | Mutation: R132H | Summary: The IDH1 R132H mutation contributes to tumor development and progression, particularly in the context of glioma.

Gene→Variant (gene-first): 3417:R132H

Genes: 3417

Variants: R132H

[Paragraph-level] PMCID: PMC8203843 Section: ABSTRACT PassageIndex: 4

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: R132H | Summary: The R132H variant is associated with sensitivity to PARP inhibitors, indicating a correlation with treatment response. Evidence Type: Oncogenic | Mutation: R132H | Summary: The R132H variant contributes to tumor development or progression, as it is implicated in cancer-related pathways.

Gene→Variant (gene-first): 3417:R132H

Genes: 3417

Variants: R132H

[Paper-level Aggregated] PMCID: PMC8078423

Evidence Type(s): Predictive

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

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

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

Genes: BRAF(673)

Variants: BRAFV600E V600E

[Paper-level Aggregated] PMCID: PMC8077124

Evidence Type(s): Predictive

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

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

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

Genes: FGFR1(2260)

Variants: p.V561M p.K656E

[Paper-level Aggregated] PMCID: PMC8040738

Evidence Type(s): Predictive

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

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

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

Genes: BRAF(673)

Variants: p.T599dup p.V600E

[Paper-level Aggregated] PMCID: PMC8033310

Evidence Type(s): Predictive

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

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

Genes: PIK3CA(5290)

Variants: E545K

[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

[Paper-level Aggregated] PMCID: PMC7612475

Evidence Type(s): Predictive

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

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

Genes: SF3B1(23451)

Variants: K700E

[Paper-level Aggregated] PMCID: PMC7612117

Evidence Type(s): Predictive

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

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

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

Genes: TP53BP1(7158) BRCA1(672)

Variants: p.L1363P p.L1407P

[Paper-level Aggregated] PMCID: PMC7568619

Evidence Type(s): Predictive

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

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

Genes: ALK(238)

Variants: L1196Q

[Paragraph-level] PMCID: PMC7568619 Section: ABSTRACT PassageIndex: 2

Evidence Type(s): Predictive, Oncogenic

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

Gene→Variant (gene-first): 238:L1196Q

Genes: 238

Variants: L1196Q

[Paper-level Aggregated] PMCID: PMC7545690

Evidence Type(s): Predictive

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

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

Genes: TYMS(7298)

Variants: rs3786362

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

Evidence Type(s): Prognostic, Predictive

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

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

Genes: 7298

Variants: rs3786362

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

Evidence Type(s): Predictive

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

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

Genes: 7298

Variants: rs3786362

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

Evidence Type(s): Predictive

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

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

Genes: 7298

Variants: rs3786362

[Paper-level Aggregated] PMCID: PMC7325368

Evidence Type(s): Predictive

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

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

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

Genes: BRAF(673) KRAS(3845)

Variants: B-RAFV600E G13D

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

Evidence Type(s): Predictive, Oncogenic

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

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

Genes: 673

Variants: B-RAFV600E

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

Evidence Type(s): Predictive, Oncogenic

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

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

Genes: 673

Variants: B-RAFV600E

[Paper-level Aggregated] PMCID: PMC7302243

Evidence Type(s): Predictive

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

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

Genes: EGFR(1956)

Variants: T790M

[Paper-level Aggregated] PMCID: PMC7294133

Evidence Type(s): Predictive

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

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

Genes: EPHB4(2050)

Variants: V871I

[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): Predictive

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

Evidence Type: Predictive

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

Genes: KRAS(3845)

Variants: G12V

[Paper-level Aggregated] PMCID: PMC7099049

Evidence Type(s): Predictive

Summary: No supporting paragraph-level outputs for evidence type Predictive.

Gene→Variant (gene-first):

Genes:

Variants:

[Paper-level Aggregated] PMCID: PMC7086303

Evidence Type(s): Predictive

Summary: Mutation: G598V | Summary: The G598V mutation in EGFR is associated with increased sensitivity to the EGFR inhibitor afatinib, indicating a correlation with treatment response.

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

Genes: EGFR(1956)

Variants: G598V

[Paragraph-level] PMCID: PMC7086303 Section: RESULTS PassageIndex: 3

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: G598V | Summary: The G598V mutation in EGFR is associated with increased sensitivity to the EGFR inhibitor afatinib, indicating a correlation with treatment response. Evidence Type: Oncogenic | 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): 1956:G598V

Genes: 1956

Variants: G598V

[Paper-level Aggregated] PMCID: PMC7081042

Evidence Type(s): Predictive

Summary: Mutation: S310F | Summary: The S310F mutation in HER2 is associated with favorable outcomes and a good response to anti-HER2 therapy, indicating its predictive value for treatment efficacy.

Evidence Type: Predictive Mutation: S310Y | Summary: The S310Y mutation in HER2 is linked to favorable outcomes and a good response to anti-HER2 therapy, suggesting it may serve as a predictive biomarker for treatment.

Evidence Type: Predictive Mutation: R678Q | Summary: The R678Q mutation in HER2 appears to correlate with favorable outcomes and a good response to anti-HER2 therapy, indicating its predictive potential for treatment response.

Evidence Type: Predictive Mutation: D769H | Summary: The D769H mutation in HER2 is associated with favorable outcomes and a good response to anti-HER2 therapy, supporting its role as a predictive marker for treatment efficacy.

Evidence Type: Predictive Mutation: I767M | Summary: The I767M mutation in HER2 is linked to favorable outcomes and a good response to anti-HER2 therapy, suggesting its predictive value for treatment effectiveness.

Evidence Type: Predictive Mutation: L755S | Summary: The L755S mutation in HER2 may confer benefits when receiving neratinib or afatinib, indicating its predictive role in treatment response.

Evidence Type: Predictive Mutation: D769Y | Summary: The D769Y mutation in HER2 could confer benefits when receiving neratinib or afatinib, suggesting its predictive value for treatment outcomes.

Gene→Variant (gene-first): ERBB2(2064):S310F ERBB2(2064):S310Y ERBB2(2064):R678Q ERBB2(2064):D769H ERBB2(2064):I767M ERBB2(2064):L755S ERBB2(2064):D769Y

Genes: ERBB2(2064)

Variants: S310F S310Y R678Q D769H I767M L755S D769Y

[Paper-level Aggregated] PMCID: PMC6843359

Evidence Type(s): Predictive

Summary: Mutation: S310F | Summary: The S310F mutant is not reactive to pertuzumab, indicating potential resistance to this therapy, while it retains binding to trastuzumab, suggesting a correlation with treatment response. Additionally, the S310F mutant's response to anti-HER2 agents, particularly the lack of effect from trastuzumab on cell proliferation, further supports its predictive role in therapy resistance.

Evidence Type: Predictive Mutation: S309A | Summary: The S309A HER2 mutant reacted with trastuzumab with reduced affinity compared to wild-type HER2, indicating a correlation with therapy response.

Evidence Type: Predictive Mutation: G309E | Summary: The G309E HER2 mutant did not bind to pertuzumab, indicating a potential resistance to this therapy.

Evidence Type: Predictive Mutation: S310Y | Summary: The S310Y HER2 mutant did not bind to pertuzumab, suggesting a potential resistance to this therapy.

Evidence Type: Predictive Mutation: G309 | Summary: The G309 HER2 mutants, including G309A and G309E, were tested for binding to pertuzumab, indicating their relevance in therapy response.

Gene→Variant (gene-first): ERBB2(2064):S310F ERBB2(2064):S309A ERBB2(2064):G309E ERBB2(2064):S310Y ERBB2(2064):G309

Genes: ERBB2(2064)

Variants: S310F S309A G309E S310Y G309

[Paper-level Aggregated] PMCID: PMC6791388

Evidence Type(s): Predictive

Summary: Mutation: S133; Ser133; Serine 133 | Summary: The increased phosphorylation of CREB at Serine 133 is speculated to promote resistance to MEK inhibitors, suggesting a correlation with treatment response.

Gene→Variant (gene-first): TP53(7157):S133 TP53(7157):Ser133 TP53(7157):Serine 133

Genes: TP53(7157)

Variants: S133 Ser133 Serine 133

[Paper-level Aggregated] PMCID: PMC6627713

Evidence Type(s): Predictive

Summary: Mutation: c.1268G>T; p.Gly423Val | Summary: The variant c.1268G>T; p.Gly423Val is associated with a complete response to first-line therapy, indicating its potential predictive value for treatment response.

Gene→Variant (gene-first): FBXW7(55294):c.1268G>T FBXW7(55294):p.Gly423Val

Genes: FBXW7(55294)

Variants: c.1268G>T p.Gly423Val

[Paragraph-level] PMCID: PMC6627713 Section: RESULTS PassageIndex: 16

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: c.1268G>T; p.Gly423Val | Summary: The variant c.1268G>T; p.Gly423Val is associated with a complete response to first-line therapy, indicating its potential predictive value for treatment response. 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.

Gene→Variant (gene-first): 55294:c.1268G>T 55294:p.Gly423Val

Genes: 55294

Variants: c.1268G>T p.Gly423Val

[Paper-level Aggregated] PMCID: PMC6549573

Evidence Type(s): Predictive

Summary: Mutation: G12D | Summary: The KRAS G12D mutation is associated with response to bortezomib therapy in non-small-cell lung cancer (NSCLC), although it is noted that this mutation alone is not a robust predictor of response. It may correlate with treatment outcomes, but it was also associated with a lack of response in the majority of patients, indicating its potential predictive value regarding therapy response.

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

Genes: KRAS(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

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

Evidence Type(s): Predictive, Oncogenic

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

Gene→Variant (gene-first): 3845:G12D

Genes: 3845

Variants: G12D

[Paper-level Aggregated] PMCID: PMC6547681

Evidence Type(s): Predictive

Summary: Mutation: G101V | Summary: The G101V mutation is associated with acquired resistance to venetoclax therapy in patients with chronic lymphocytic leukaemia, indicating its predictive value for treatment response. It is linked to reduced affinity for venetoclax and a significantly higher LC50 concentration for the drug S55746, suggesting it may influence the response to this therapy.

Evidence Type: Predictive Mutation: F104L | Summary: The F104L mutation shows a significant change in venetoclax affinity, suggesting it may contribute to resistance against the drug.

Evidence Type: Predictive Mutation: F104C | Summary: The F104C mutation demonstrates altered venetoclax affinity, which implies a role in resistance to therapy.

Evidence Type: Predictive Mutation: E152 | Summary: The variant E152 is associated with venetoclax affinity, suggesting it may correlate with response or sensitivity to this specific therapy.

Gene→Variant (gene-first): BCL2(596):G101V BCL2(596):F104L BCL2(596):F104C BCL2(596):E152

Genes: BCL2(596)

Variants: G101V F104L F104C E152

[Paragraph-level] PMCID: PMC6547681 Section: RESULTS PassageIndex: 12

Evidence Type(s): Functional, Predictive, Oncogenic

Summary: Evidence Type: Functional | Mutation: G101V | Summary: The G101V mutation alters the binding affinity of the BCL-2 protein to the selective antagonist S55746, indicating a change in molecular function compared to the wild-type. Evidence Type: Predictive | Mutation: G101V | Summary: The G101V mutation is associated with a significantly higher LC50 concentration for the drug S55746, suggesting that it may influence the response to this therapy. Evidence Type: Oncogenic | Mutation: G101V | Summary: The G101V mutation in BCL-2 is implicated in altering the drug binding characteristics, which may contribute to tumor development or progression.

Gene→Variant (gene-first): 596:G101V

Genes: 596

Variants: G101V

[Paragraph-level] PMCID: PMC6547681 Section: RESULTS PassageIndex: 9

Evidence Type(s): Predictive

Summary: Evidence Type: Predictive | Mutation: E152 | Summary: The variant E152 is associated with venetoclax affinity, suggesting it may correlate with response or sensitivity to this specific therapy.

Gene→Variant (gene-first): 596:E152

Genes: 596

Variants: E152

[Paragraph-level] PMCID: PMC6547681 Section: RESULTS PassageIndex: 8

Evidence Type(s): Predictive

Summary: Evidence Type: Predictive | Mutation: G101V | Summary: The G101V mutation is associated with reduced affinity for venetoclax, indicating a potential resistance to therapy. Evidence Type: Predictive | Mutation: F104L | Summary: The F104L mutation shows a significant change in venetoclax affinity, suggesting it may contribute to resistance against the drug. Evidence Type: Predictive | Mutation: F104C | Summary: The F104C mutation demonstrates altered venetoclax affinity, which implies a role in resistance to therapy.

Gene→Variant (gene-first): 596:F104C 596:F104L 596:G101V

Genes: 596

Variants: F104C F104L G101V

[Paper-level Aggregated] PMCID: PMC6478919

Evidence Type(s): Predictive

Summary: Mutation: T > C variation at position 21 | Summary: The T > C variation at position 21 of the BCL2 sequence is associated with predicting response to the chemotherapy drug paclitaxel, correlating with both resistance and increased sensitivity to the drug. The presence of this variant is linked to increased BCL2 expression and transcript abundance when treated with paclitaxel, indicating its predictive value for therapy response.

Evidence Type: Predictive Mutation: rs1801018 | Summary: The variant rs1801018 is associated with resistance to paclitaxel and response to different treatments in ovarian cancer cell lines, indicating its potential predictive value for therapy sensitivity.

Gene→Variant (gene-first): BCL2(596):T > C variation at position 21 BCL2(596):rs1801018

Genes: BCL2(596)

Variants: T > C variation at position 21 rs1801018

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 28

Evidence Type(s): Predictive

Summary: Evidence Type: Predictive | Mutation: rs1801018 | Summary: The rs1801018 variant is associated with response to different treatments in ovarian cancer cell lines, indicating its potential predictive value for therapy sensitivity.

Gene→Variant (gene-first): 596:(AUC) of 39 596:rs1801018

Genes: 596

Variants: (AUC) of 39 rs1801018

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 25

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: 21 T > C | Summary: The 21 T > C variant is associated with increased BCL2 expression and correlates with resistance to paclitaxel treatment, indicating its predictive value for therapy response. Evidence Type: Oncogenic | Mutation: 21 T > C | Summary: The 21 T > C variant contributes to tumor development by leading to higher BCL2 expression, which is linked to resistance against paclitaxel, a common chemotherapeutic agent.

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

Genes: 596

Variants: 21 T > C

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 24

Evidence Type(s): Predictive

Summary: Evidence Type: Predictive | Mutation: 21 T > C | Summary: The presence of the 21 T > C variant correlates with increased abundance of transcripts when treated with paclitaxel, suggesting a potential relationship with treatment response.

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

Genes: 596

Variants: 21 T > C

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 22

Evidence Type(s): Predictive, Functional

Summary: Evidence Type: Predictive | Mutation: 21 T > C | Summary: The variant 21 T > C in the BCL2 sequence correlates with increased sensitivity to paclitaxel, suggesting a potential predictive role in therapy response. Evidence Type: Functional | Mutation: 21 T > C | Summary: The 21 T > C variant leads to a more stable BCL2 transcript, which may result in higher protein levels, indicating an alteration in molecular function.

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

Genes: 596

Variants: 21 T > C

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 7

Evidence Type(s): Predictive

Summary: Evidence Type: Predictive | Mutation: T instead of a C | Summary: The variant T instead of a C correlates with patient resistance to paclitaxel, allowing for retrospective prediction of treatment response and the number of treatment lines received. Evidence Type: Predictive | Mutation: rs1801018 | Summary: The variant rs1801018 is associated with resistance to paclitaxel, indicating its predictive value for treatment response in patients.

Gene→Variant (gene-first): 596:T instead of a C 596:rs1801018

Genes: 596

Variants: T instead of a C rs1801018

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 6

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: + 21 T > C | Summary: The mutation from C to T at location 21 of BCL2 is associated with resistance to the chemotherapy drug paclitaxel, indicating its predictive value for treatment response. Evidence Type: Oncogenic | Mutation: + 21 T > C | Summary: The transition from C to T at location 21 of BCL2 contributes to tumor development or progression, highlighting its oncogenic potential.

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

Genes: 596

Variants: + 21 T > C C to a T

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 2

Evidence Type(s): Predictive

Summary: Evidence Type: Predictive | Mutation: T > C variation at position 21 | Summary: The T > C variation at position 21 of the BCL2 sequence is associated with predicting response to the chemotherapy drug paclitaxel.

Gene→Variant (gene-first): 596:T > C variation at position 21

Genes: 596

Variants: T > C variation at position 21

[Paper-level Aggregated] PMCID: PMC6368247

Evidence Type(s): Predictive

Summary: Mutation: Y537S | Summary: The Y537S mutation is associated with resistance to CDK4/6 inhibitors and fulvestrant treatment, indicating its predictive value in therapy response and correlation with treatment selection in patients with advanced estrogen receptor positive breast cancer.

Gene→Variant (gene-first): PTEN(5728):Y537S

Genes: PTEN(5728)

Variants: Y537S

[Paragraph-level] PMCID: PMC6368247 Section: RESULTS PassageIndex: 17

Evidence Type(s): Predictive, Oncogenic, Prognostic

Summary: Evidence Type: Predictive | Mutation: Y537S | Summary: The Y537S mutation is associated with resistance to fulvestrant treatment, indicating its predictive value in therapy response. Evidence Type: Oncogenic | Mutation: Y537S | Summary: The Y537S mutation contributes to tumor development or progression, as it is positively selected during treatment. Evidence Type: Prognostic | Mutation: Y537S | Summary: The presence of the Y537S mutation correlates with progression-free survival outcomes, suggesting its prognostic significance.

Gene→Variant (gene-first): 5728:Y537S

Genes: 5728

Variants: Y537S

[Paragraph-level] PMCID: PMC6368247 Section: RESULTS PassageIndex: 15

Evidence Type(s): Predictive

Summary: Evidence Type: Predictive | Mutation: Y537S | Summary: The variant Y537S is associated with treatment selection, indicating a correlation with response or resistance to specific therapies.

Gene→Variant (gene-first): 5728:Y537S

Genes: 5728

Variants: Y537S

[Paper-level Aggregated] PMCID: PMC6280667

Evidence Type(s): Predictive

Summary: Mutation: TP53 | Summary: TP53 mutations were shown to cause a broad pattern of drug resistance, with some drugs trending more sensitive to TP53 mutant cases, indicating a correlation with treatment response.

Evidence Type: Predictive Mutation: ASXL1 | Summary: ASXL1 mutations were associated with drug resistance, but also showed sensitivity to specific drugs, suggesting a predictive role in treatment response.

Evidence Type: Predictive Mutation: NRAS | Summary: NRAS mutations correlated largely with resistance to most drugs, but also showed predicted sensitivity to MAPK inhibitors, indicating a potential predictive value for therapy.

Evidence Type: Predictive Mutation: KRAS | Summary: KRAS mutations were associated with resistance to most drugs, while also showing sensitivity to MAPK inhibitors, suggesting a predictive role in treatment response.

Evidence Type: Predictive Mutation: IDH2 | Summary: IDH2 mutations conferred sensitivity to a broad spectrum of drugs, indicating a predictive association with treatment response.

Evidence Type: Predictive Mutation: IDH1 | Summary: IDH1 mutations were associated with resistance to most drugs, suggesting a predictive role in treatment response.

Evidence Type: Predictive Mutation: RUNX1 | Summary: RUNX1 mutations correlated with sensitivity to PIK3C/MTOR inhibitors, indicating a predictive association with treatment response.

Evidence Type: Predictive Mutation: FLT3 | Summary: FLT3 mutations exhibited a significant pattern of co-occurrence with sensitivity to the FDA approved drug, ibrutinib, indicating a predictive role in treatment response.

Evidence Type: Predictive Mutation: NPM1 | Summary: NPM1 mutations were significantly more sensitive to ibrutinib compared to wild type, suggesting a predictive association with treatment response.

Evidence Type: Predictive Mutation: BCOR | Summary: BCOR mutations showed sensitivity to alternative drugs, indicating a predictive role in treatment response, particularly in specific combinatorial mutation settings.

Gene→Variant (gene-first): NA:TP53 NA:ASXL1 NA:NRAS NA:KRAS NA:IDH2 NA:IDH1 NA:RUNX1 NA:FLT3 NA:NPM1 NA:BCOR

Genes: NA

Variants: TP53 ASXL1 NRAS KRAS IDH2 IDH1 RUNX1 FLT3 NPM1 BCOR

[Paper-level Aggregated] PMCID: PMC5873857

Evidence Type(s): Predictive

Summary: Mutation: BRAFV600E | Summary: The BRAFV600E mutation correlates with response to vemurafenib treatment, an approved BRAF inhibitor, as zebrafish with this mutation exhibited improved blood flow following therapy.

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

Genes: BRAF(673)

Variants: BRAFV600E

[Paragraph-level] PMCID: PMC5873857 Section: RESULTS PassageIndex: 6

Evidence Type(s): Oncogenic, Predictive

Summary: 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. Evidence Type: Predictive | Mutation: BRAFV600E | Summary: The BRAFV600E mutation correlates with response to vemurafenib treatment, an approved BRAF inhibitor, as zebrafish with this mutation exhibited improved blood flow following therapy.

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

Genes: 673

Variants: BRAFV600E

[Paper-level Aggregated] PMCID: PMC5820258

Evidence Type(s): Predictive

Summary: Mutation: p.K601E | Summary: The BRAF p.K601E mutation correlates with response to venetoclax therapy, indicating its potential role in guiding treatment options.

Evidence Type: Predictive Mutation: p.E46K | Summary: The p.E46K mutation in BTG1 is associated with the development of a dominant clone at relapse, suggesting its involvement in resistance to venetoclax treatment.

Evidence Type: Predictive Mutation: BRAFV600E | Summary: The BRAFV600E mutation is associated with venetoclax resistance, indicating a correlation with treatment response.

Gene→Variant (gene-first): BRAF(673):p.K601E TP53(7157):p.E46K BRAF(673):BRAFV600E

Genes: BRAF(673) TP53(7157)

Variants: p.K601E p.E46K BRAFV600E

[Paper-level Aggregated] PMCID: PMC5792548

Evidence Type(s): Predictive

Summary: Mutation: T790M | Summary: The EGFR T790M mutation is associated with resistance to the standard treatment osimeritinib in non-small cell lung cancer, indicating its predictive role in therapy response.

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

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

Genes: EGFR(1956)

Variants: T790M C797S

[Paragraph-level] PMCID: PMC5792548 Section: RESULTS PassageIndex: 4

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: C797S | Summary: The C797S mutation is associated with resistance to osimertinib, indicating its role in therapy response. 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): 1956:C797S

Genes: 1956

Variants: C797S

[Paper-level Aggregated] PMCID: PMC5762309

Evidence Type(s): Predictive

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

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

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

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

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

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

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

Genes: KIT(3815)

Variants: V559D L576P V654A N822K D816V T670I

[Paper-level Aggregated] PMCID: PMC5652823

Evidence Type(s): Predictive

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

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

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

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

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

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

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

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

Genes: EGFR(1956)

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

[Paragraph-level] PMCID: PMC5652823 Section: RESULTS PassageIndex: 25

Evidence Type(s): Predictive, Prognostic

Summary: Evidence Type: Predictive | Mutation: T790M | Summary: The T790M mutation is associated with treatment response to osimertinib, as evidenced by the observed partial remissions and stable disease in patients treated with this therapy. Evidence Type: Prognostic | Mutation: T790M | Summary: The T790M mutation may correlate with disease outcome, as indicated by the progression-free survival (PFS) and overall survival (OS) data, although specific median values have not been reached.

Gene→Variant (gene-first): 1956:T790M

Genes: 1956

Variants: T790M

[Paragraph-level] PMCID: PMC5652823 Section: RESULTS PassageIndex: 24

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: T790M | Summary: The T790M mutation is associated with acquired resistance to 1st/2nd generation EGFR-TKI therapy and correlates with response to the third generation EGFR-TKI osimertinib. Evidence Type: Oncogenic | Mutation: T790M | Summary: The T790M mutation contributes to tumor development and progression, particularly in the context of resistance to EGFR-TKI therapy. 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: V600E | Summary: The V600E mutation in the BRAF gene is associated with tumor development and progression, particularly in the context of the patient's cancer. 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): 1956:G719C 1956:T790M 673:V600E 1956:c.2155G>T 1956:p.G719C 7157:p.R248W

Genes: 1956 673 7157

Variants: G719C T790M V600E c.2155G>T p.G719C p.R248W

[Paragraph-level] PMCID: PMC5652823 Section: RESULTS PassageIndex: 17

Evidence Type(s): Predictive

Summary: Evidence Type: Predictive | Mutation: E709A | Summary: The E709A mutation is associated with a sensitizing driver mutation that correlates with response to targeted therapy in patients. Evidence Type: Predictive | Mutation: G719S | Summary: The G719S mutation is associated with a sensitizing driver mutation that correlates with response to targeted therapy in patients.

Gene→Variant (gene-first): 1956:E709A 1956:G719S

Genes: 1956

Variants: E709A G719S

[Paragraph-level] PMCID: PMC5652823 Section: RESULTS PassageIndex: 11

Evidence Type(s): Oncogenic, Predictive

Summary: Evidence Type: Oncogenic | Mutation: c.2527G>A; p.V843I | Summary: The c.2527G>A; p.V843I mutation is described as activating from a biological perspective, indicating its contribution to tumor development or progression in lung cancer. Evidence Type: Predictive | Mutation: c.2527G>A; p.V843I | Summary: Although the c.2527G>A; p.V843I mutation is activating, it does not confer sensitivity to EGFR-TKIs, which relates to its predictive value regarding therapy response.

Gene→Variant (gene-first): 1956:c.2527G>A 1956:p.V843I

Genes: 1956

Variants: c.2527G>A p.V843I

[Paragraph-level] PMCID: PMC5652823 Section: RESULTS PassageIndex: 10

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: c.2543C>T; p.P848L | Summary: The mutation c.2543C>T; p.P848L is associated with a patient's response to erlotinib, indicating its predictive value for treatment outcomes. Evidence Type: Oncogenic | Mutation: c.2543C>T; p.P848L | Summary: The mutation has been previously described in lung samples, suggesting its role in tumor development or progression, thus supporting its classification as oncogenic.

Gene→Variant (gene-first): 1956:c.2543C>T 1956:p.P848L

Genes: 1956

Variants: c.2543C>T p.P848L

[Paragraph-level] PMCID: PMC5652823 Section: RESULTS PassageIndex: 9

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: c.2258T>C; p.P753L | Summary: The mutation c.2258T>C; p.P753L was associated with treatment using erlotinib, indicating a potential correlation with resistance or sensitivity to this therapy. Evidence Type: Oncogenic | Mutation: c.2258T>C; p.P753L | Summary: The mutation is noted in the context of a patient with stage IIIA SCC, suggesting its contribution to tumor development or progression in lung cancer.

Gene→Variant (gene-first): 1956:c.2258T>C 1956:p.P753L

Genes: 1956

Variants: c.2258T>C p.P753L

[Paragraph-level] PMCID: PMC5652823 Section: RESULTS PassageIndex: 8

Evidence Type(s): Oncogenic, Predictive

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

Gene→Variant (gene-first): 1956:c.2203G>A 1956:p.G735S

Genes: 1956

Variants: c.2203G>A p.G735S

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

Evidence Type(s): Predictive, Oncogenic

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

Gene→Variant (gene-first): 1956:T790M

Genes: 1956

Variants: T790M

[Paper-level Aggregated] PMCID: PMC5629366

Evidence Type(s): Predictive

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

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

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

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

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

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

Genes: IDH1(3417)

Variants: R132C R132G R132H R132L R132S

[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

[Paragraph-level] PMCID: PMC5629366 Section: RESULTS PassageIndex: 17

Evidence Type(s): Predictive, Functional

Summary: Evidence Type: Predictive | Mutation: R132H | Summary: The R132H mutation in IDH1 is associated with sensitivity to the treatment with BAY1436032, indicating a correlation with therapeutic response in AML cells. Evidence Type: Functional | Mutation: R132H | Summary: The R132H mutation alters the histone methylation phenotype in AML cells, demonstrating a change in molecular function related to histone trimethylation levels.

Gene→Variant (gene-first): 3417:R132H

Genes: 3417

Variants: R132H

[Paragraph-level] PMCID: PMC5629366 Section: RESULTS PassageIndex: 3

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: R132C | Summary: The R132C mutation in IDH1 is associated with sensitivity to the IDH1 inhibitor BAY1436032, indicating a predictive relationship for therapy response. Evidence Type: Predictive | Mutation: R132G | Summary: The R132G mutation in IDH1 shows sensitivity to the IDH1 inhibitor BAY1436032, suggesting it is predictive of treatment response. Evidence Type: Predictive | Mutation: R132H | Summary: The R132H mutation in IDH1 correlates with sensitivity to the IDH1 inhibitor BAY1436032, indicating a predictive relationship for therapy response. Evidence Type: Predictive | Mutation: R132L | Summary: The R132L mutation in IDH1 is linked to sensitivity to the IDH1 inhibitor BAY1436032, suggesting a predictive relationship for treatment response. Evidence Type: Predictive | Mutation: R132S | Summary: The R132S mutation in IDH1 is associated with sensitivity to the IDH1 inhibitor BAY1436032, indicating a predictive relationship for therapy response. Evidence Type: Oncogenic | 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, 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.

Gene→Variant (gene-first): 3417:R132C 3417:R132G 3417:R132H 3417:R132L 3417:R132S 3418:R140Q

Genes: 3417 3418

Variants: R132C R132G R132H R132L R132S R140Q

[Paper-level Aggregated] PMCID: PMC5613053

Evidence Type(s): Predictive

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

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

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

Genes: FLT3(2322)

Variants: D835Y F691

[Paragraph-level] PMCID: PMC5613053 Section: RESULTS PassageIndex: 12

Evidence Type(s): Predictive, Functional

Summary: Evidence Type: Predictive | Mutation: D835Y | Summary: The mutation D835Y is associated with the response to gilteritinib, a type 1 FLT3 inhibitor, indicating its predictive value for therapy. Evidence Type: Predictive | Mutation: D835 | Summary: The mutation D835 is implicated in the response to gilteritinib, suggesting its role in predicting treatment outcomes. Evidence Type: Functional | Mutation: F691 | Summary: The F691 position is noted for its hydrophobic interaction with gilteritinib, indicating a functional alteration in the molecular interaction with the drug.

Gene→Variant (gene-first): 2322:D835 2322:D835Y 2322:F691

Genes: 2322

Variants: D835 D835Y F691

[Paragraph-level] PMCID: PMC5613053 Section: RESULTS PassageIndex: 10

Evidence Type(s): Predictive

Summary: Evidence Type: Predictive | Mutation: D835Y | Summary: The D835Y mutation is associated with resistance to FLT3 inhibitors, indicating a correlation with treatment response and sensitivity to gilteritinib. Evidence Type: Predictive | Mutation: F691 | Summary: The F691 mutation is implicated in resistance to FLT3 inhibitors, suggesting it affects the response to gilteritinib treatment. Evidence Type: Predictive | Mutation: F691 L | Summary: The F691 L mutation is associated with resistance to FLT3 inhibitors, indicating a correlation with treatment response and sensitivity to gilteritinib. Evidence Type: Predictive | Mutation: F691I | Summary: The F691I mutation is implicated in resistance to FLT3 inhibitors, suggesting it affects the response to gilteritinib treatment.

Gene→Variant (gene-first): 2322:D835Y 2322:F691 2322:F691 L 2322:F691I

Genes: 2322

Variants: D835Y F691 F691 L F691I

[Paragraph-level] PMCID: PMC5613053 Section: RESULTS PassageIndex: 9

Evidence Type(s): Predictive

Summary: Evidence Type: Predictive | Mutation: D835Y | Summary: The D835Y mutation is associated with the response to gilteritinib, indicating its predictive value for therapy sensitivity. Evidence Type: Predictive | Mutation: F691 L/I | Summary: The F691 L/I mutation is associated with the response to gilteritinib, indicating its predictive value for therapy sensitivity.

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

Genes: 2322

Variants: D835Y F691 L/I

[Paper-level Aggregated] PMCID: PMC5355930

Evidence Type(s): Predictive

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

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

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

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

Genes: PIK3CA(5290)

Variants: H1047R E545K E542K

[Paper-level Aggregated] PMCID: PMC5122709

Evidence Type(s): Predictive

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

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

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

Genes: BRAF(673) NA

Variants: V600E BRAFV600E

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

Evidence Type(s): Predictive, Oncogenic

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

Gene→Variant (gene-first): 673:V600

Genes: 673

Variants: V600

[Paper-level Aggregated] PMCID: PMC5083195

Evidence Type(s): Predictive

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

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

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

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

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

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

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

Genes: LRRC7(57554) NA CDH4(1002)

Variants: rs7515290 rs1374679 rs10979372 rs1122269 rs9637468 rs4925193

[Paragraph-level] PMCID: PMC5083195 Section: RESULTS PassageIndex: 16

Evidence Type(s): Predictive, Functional

Summary: Evidence Type: Predictive | Mutation: rs1122269 | Summary: The SNP rs1122269 in the CDH4 gene correlates with the response to gemcitabine treatment, indicating its potential as a predictive biomarker for therapy response. Evidence Type: Functional | Mutation: rs1122269 | Summary: The variant rs1122269 affects CDH4 expression levels in lymphoblastoid cell lines after exposure to gemcitabine, demonstrating a functional impact on molecular expression.

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

Genes: 1002

Variants: rs1122269

[Paragraph-level] PMCID: PMC5083195 Section: RESULTS PassageIndex: 10

Evidence Type(s): Predictive

Summary: Evidence Type: Predictive | Mutation: rs9637468 | Summary: The variant rs9637468 is associated with gemcitabine response during pancreatic cancer therapy, indicating its potential as a genetic biomarker for predicting treatment outcomes. Evidence Type: Predictive | Mutation: rs4925193 | Summary: The variant rs4925193 is associated with gemcitabine response during pancreatic cancer therapy, suggesting its role as a genetic biomarker for predicting treatment outcomes.

Gene→Variant (gene-first): 1002:rs4925193 NA:rs9637468

Genes: 1002 NA

Variants: rs4925193 rs9637468

[Paragraph-level] PMCID: PMC5083195 Section: RESULTS PassageIndex: 7

Evidence Type(s): Predictive

Summary: Evidence Type: Predictive | Mutation: rs7515290 | Summary: The SNP rs7515290 showed trends associated with gemcitabine IC50 values, indicating a potential correlation with drug response in pancreatic cancer. Evidence Type: Predictive | Mutation: rs1374679 | Summary: The SNP rs1374679 demonstrated trends associated with gemcitabine IC50 values, suggesting a possible link to drug response in pancreatic cancer. Evidence Type: Predictive | Mutation: rs10979372 | Summary: The SNP rs10979372 was associated with gemcitabine IC50 values, indicating its potential role in influencing drug response in pancreatic cancer. Evidence Type: Predictive | Mutation: rs1122269 | Summary: The SNP rs1122269 showed trends related to gemcitabine IC50 values, implying a potential impact on drug response in pancreatic cancer.

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

Genes: NA 1002 57554

Variants: rs10979372 rs1122269 rs1374679 rs7515290

[Paper-level Aggregated] PMCID: PMC5029699

Evidence Type(s): Predictive

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

Evidence Type: Predictive Mutation: I538V | Summary: The I538V mutation is associated with measurements of Ki values for various FGFR3 inhibitors, indicating its potential role in influencing response to therapy.

Evidence Type: Predictive Mutation: K650E | Summary: The K650E mutation had moderate effects on the efficacy of all inhibitors, reducing the efficacy of FGFR-specific inhibitors AZD4547 and JNJ42756493, indicating a correlation with treatment response and resistance.

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

Evidence Type: Predictive Mutation: N540S | Summary: The N540S mutation had a pronounced effect on the efficacy of JNJ42756493, indicating its impact on treatment response.

Evidence Type: Predictive

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

Genes: FGFR3(2261) FGFR2(2263)

Variants: V555M I538V K650E N540K N540S

[Paper-level Aggregated] PMCID: PMC5021039

Evidence Type(s): Predictive

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

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

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

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

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

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

Genes: EGFR(1956)

Variants: E709K G719X L858R L861Q S768I

[Paragraph-level] PMCID: PMC5021039 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Predictive

Summary: Evidence Type: Predictive | Mutation: E709K | Summary: E709K is associated with moderate sensitivity to gefitinib or erlotinib, indicating its predictive value for response to these therapies. Evidence Type: Predictive | Mutation: G719X | Summary: G719X shows moderate sensitivities to gefitinib or erlotinib, suggesting it may predict response to these targeted therapies. Evidence Type: Predictive | Mutation: L858R | Summary: L858R is a common mutation that has been established to correlate with response to EGFR-tyrosine kinase inhibitors, indicating its predictive value. Evidence Type: Predictive | Mutation: L861Q | Summary: L861Q demonstrates moderate sensitivities to gefitinib or erlotinib, indicating its predictive value for response to these therapies. Evidence Type: Predictive | Mutation: S768I | Summary: S768I is associated with moderate sensitivities to gefitinib or erlotinib, suggesting it may predict response to these targeted therapies.

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

Genes: 1956

Variants: E709K G719X L858R L861Q S768I

[Paper-level Aggregated] PMCID: PMC5002925

Evidence Type(s): Predictive

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

Evidence Type: Predictive

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

Genes: ERBB2(2064)

Variants: p.L755S

[Paper-level Aggregated] PMCID: PMC4899144

Evidence Type(s): Predictive

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

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

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

Genes: EZH2(2146)

Variants: Y641F Y646F

[Paragraph-level] PMCID: PMC4899144 Section: RESULTS PassageIndex: 13

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: Y641F | Summary: The Y641F mutation in EZH2 is associated with response to the EZH2 inhibitor JQEZ5, indicating its predictive value for treatment efficacy in B-cell lymphoma and melanoma models. Evidence Type: Oncogenic | Mutation: Y641F | Summary: The Y641F mutation in EZH2 contributes to tumor development in B-cell lymphoma, as evidenced by its presence in autochthonous tumor models.

Gene→Variant (gene-first): 2146:Y641F

Genes: 2146

Variants: Y641F

[Paragraph-level] PMCID: PMC4899144 Section: RESULTS PassageIndex: 12

Evidence Type(s): Predictive, Oncogenic, Functional

Summary: Evidence Type: Predictive | Mutation: Y641F | Summary: The Y641F mutation in Ezh2 is associated with increased sensitivity to the EZH2 inhibitor JQEZ5, indicating a correlation with treatment response. Evidence Type: Oncogenic | Mutation: Y641F | Summary: The Y641F mutation in Ezh2 is implicated in tumor initiation and maintenance, contributing to tumor development in melanoma. Evidence Type: Functional | Mutation: Y641F | Summary: The Y641F mutation alters the enzymatic activity of Ezh2, as evidenced by the differential response to EZH2 inhibitors in cell lines. Evidence Type: Predictive | Mutation: Y646F | Summary: The Y646F mutation exhibits in vitro activity against the JQEZ5 inhibitor, suggesting a correlation with treatment response. Evidence Type: Oncogenic | Mutation: Y646F | Summary: The Y646F mutation in Ezh2 is involved in tumor development and progression in melanoma. Evidence Type: Functional | Mutation: Y646F | Summary: The Y646F mutation affects the molecular function of Ezh2, as indicated by its response to pharmacological inhibitors.

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

Genes: 2146

Variants: Y641F Y646F