Gene Variant Detail

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Gene FGFR2
Variant L617M
Impact List missense
Protein Effect unknown
Gene Variant Descriptions FGFR2 L617M lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). L617M has been demonstrated to confer resistance to FGFR inhibitors as a secondary resistance mutation in the context of FGFR2 fusions (PMID: 31911531), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Jan 2020).
Associated Drug Resistance Y

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Transcript NM_000141
gDNA chr10:g.121496546A>T
cDNA c.1849T>A
Protein p.L617M
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_000141 chr10:g.121496546A>T c.1849T>A p.L617M RefSeq GRCh38/hg38
XM_006717712 chr10:g.121485454_121485456delAAGinsCAT c.1849_1851delCTTinsATG p.L617M RefSeq GRCh38/hg38
XM_017015925 chr10:g.121485447G>T c.1849C>A p.L617M RefSeq GRCh38/hg38
NM_001144916 chr10:g.121485396G>T c.1849C>A p.L617M RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
FGFR2 - SHTN1 FGFR2 E565A FGFR2 L617M Advanced Solid Tumor sensitive Infigratinib + Sapanisertib Preclinical - Cell culture Actionable In a preclinical study, the addition of Sapanisertib (MLN0128) therapy restored the sensitivity of transformed cells expressing both FGFR2-SHTN1 and FGFR2 E565A to treatment with Infigratinib (BGJ398), demonstrating synergistic effects (PMID: 31911531). 31911531
FGFR2 - SHTN1 FGFR2 E565A FGFR2 L617M cholangiocarcinoma predicted - resistant Infigratinib Case Reports/Case Series Actionable In a Phase II trial, a patient with cholangiocarcinoma harboring FGFR2-SHTN1 initially responded to treatment with Infigratinib (BGJ398), but progressed after eight months and via repeat tissue biopsy was found to have acquired FGFR2 E565A, and via circulating tumor DNA testing, FGFR2 L617M (PMID: 31911531). 31911531
FGFR2 - SHTN1 FGFR2 L617M Advanced Solid Tumor sensitive Erdafitinib + Sapanisertib Preclinical - Cell culture Actionable In a preclinical study, the addition of Sapanisertib (MLN0128) therapy restored the sensitivity of transformed cells expressing both FGFR2-SHTN1 and FGFR2 L617M to treatment with Balversa (erdafitinib), demonstrating synergistic effects (PMID: 31911531). 31911531
FGFR2 - SHTN1 FGFR2 L617M Advanced Solid Tumor resistant Infigratinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing both FGFR2-SHTN1 and FGFR2 L617M demonstrated resistance to treatment with Infigratinib (BGJ398) in culture (PMID: 31911531). 31911531
FGFR2 - SHTN1 FGFR2 L617M Advanced Solid Tumor sensitive Infigratinib + Sapanisertib Preclinical - Cell culture Actionable In a preclinical study, the addition of Sapanisertib (MLN0128) therapy restored the sensitivity of transformed cells expressing both FGFR2-SHTN1 and FGFR2 L617M to treatment with Infigratinib (BGJ398), demonstrating synergistic effects (PMID: 31911531). 31911531
FGFR2 - SHTN1 FGFR2 L617M cholangiocarcinoma resistant AZD4547 Preclinical - Cell culture Actionable In a preclinical study, cholangiocarcinoma cells expressing both FGFR2-SHTN1 and FGFR2 L617M demonstrated resistance to treatment with AZD4547 in culture (PMID: 31911531). 31911531
FGFR2 - SHTN1 FGFR2 L617M cholangiocarcinoma resistant Erdafitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing both FGFR2-SHTN1 and FGFR2 L617M demonstrated resistance to treatment with Balversa (erdafitinib) in culture (PMID: 31911531). 31911531
FGFR2 - SHTN1 FGFR2 L617M cholangiocarcinoma sensitive Ponatinib Preclinical - Cell culture Actionable In a preclinical study, cholangiocarcinoma cells expressing both FGFR2-SHTN1 and FGFR2 E565A were sensitive to treatment with Iclusig (ponatinib) in culture, demonstrating reduced cell viability (PMID: 31911531). 31911531
FGFR2 - SHTN1 FGFR2 L617M Advanced Solid Tumor sensitive Ponatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing both FGFR2-SHTN1 and FGFR2 L617M were sensitive to treatment with Iclusig (ponatinib) in culture, demonstrating reduced cell viability (PMID: 31911531). 31911531
FGFR2 - SHTN1 FGFR2 L617M Advanced Solid Tumor sensitive Ponatinib + Sapanisertib Preclinical - Cell culture Actionable In a preclinical study, the combination therapy of Iclusig (ponatinib) and Sapanisertib (MLN0128) resulted in synergistic effects in transformed cells expressing both FGFR2-SHTN1 and FGFR2 L617M in culture (PMID: 31911531). 31911531
FGFR2 - SHTN1 FGFR2 L617M Advanced Solid Tumor resistant Erdafitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing both FGFR2-SHTN1 and FGFR2 L617M demonstrated resistance to treatment with Balversa (erdafitinib) in culture (PMID: 31911531). 31911531
FGFR2 - SHTN1 FGFR2 L617M cholangiocarcinoma resistant Futibatinib Preclinical - Cell culture Actionable In a preclinical study, cholangiocarcinoma cells expressing both FGFR2-SHTN1 and FGFR2 L617M demonstrated resistance to treatment with Futibatinib (TAS-120) in culture (PMID: 31911531). 31911531
FGFR2 - SHTN1 FGFR2 L617M Advanced Solid Tumor sensitive AZD4547 + Sapanisertib Preclinical - Cell culture Actionable In a preclinical study, the addition of Sapanisertib (MLN0128) therapy restored the sensitivity of transformed cells expressing both FGFR2-SHTN1 and FGFR2 L617M to treatment with AZD4547, demonstrating synergistic effects (PMID: 31911531). 31911531
FGFR2 - SHTN1 FGFR2 L617M cholangiocarcinoma resistant Infigratinib Preclinical - Cell culture Actionable In a preclinical study, cholangiocarcinoma cells expressing both FGFR2-SHTN1 and FGFR2 L617M demonstrated resistance to treatment with Infigratinib (BGJ398) in culture (PMID: 31911531). 31911531
FGFR2 - SHTN1 FGFR2 L617M Advanced Solid Tumor resistant AZD4547 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing both FGFR2-SHTN1 and FGFR2 L617M demonstrated resistance to treatment with AZD4547 in culture (PMID: 31911531). 31911531
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
FGFR2 mutant Advanced Solid Tumor sensitive Pemigatinib Preclinical - Cell culture Actionable In a preclinical study, a variety of cancer cell lines harboring mutations in FGFR1, FGFR2, and/or FGFR3 demonstrated sensitivity to Pemazyre (pemigatinib) in culture and in cell line xenograft models, resulting in inhibition of tumor growth (Cancer Res 2015;75(15 Suppl):Abstract nr 771). detail...
FGFR2 mutant endometrial cancer sensitive Infigratinib Preclinical Actionable In a preclinical study, Infigratinib (BGJ398) inhibited the growth of FGFR2-mutated endometrial cancer cells in vitro and in xenograft models (PMID: 23443805). 23443805
FGFR2 mutant cholangiocarcinoma predicted - sensitive Erdafitinib Phase I Actionable In a Phase I trial, Balversa (erdafitinib) treatment resulted in an objective response rate of 27% (3/11) in patients with cholangiocarcinoma harboring FGFR genomic alterations, including 1 with FGFR2 mutation, 2 with FGFR3 mutations, and 8 with FGFR2 fusions (PMID: 31088831; NCT01703481). 31088831
FGFR2 mutant Advanced Solid Tumor predicted - sensitive Debio 1347 Phase I Actionable In a Phase I trial, Debio 1347 treatment resulted in partial response in 10.5% (6/57) and stable disease in 28.1% (16/57) of patients with advanced solid tumors harboring genomic alterations of FGFR1/2/3, including amplifications, fusions, and mutations (PMID: 30745300; NCT01948297). 30745300
FGFR2 mutant transitional cell carcinoma sensitive Erdafitinib FDA approved - Has Companion Diagnostic Actionable In a Phase II trial (BCL2001) that supported FDA approval, Balversa (erdafitinib) treatment resulted in an objective response rate of 40% (40/99, 3 complete response, 37 partial response) and a disease control rate of 80% in patients with metastatic or unresectable urothelial carcinoma harboring FGFR alterations (PMID: 31340094; NCT02365597). detail... 31340094 detail...
FGFR2 mutant transitional cell carcinoma sensitive Erdafitinib Guideline Actionable Balversa (erdafitinib) is included in the guidelines for patients with advanced or metastatic urothelial carcinoma harboring Fgfr2 alterations after progression on platinum-based regimens (NCCN.org). detail...
FGFR2 mutant bladder urothelial carcinoma sensitive Erdafitinib Guideline Actionable Balversa (erdafitinib) is included in the guidelines for patients with advanced or metastatic urothelial carcinoma harboring Fgfr2 alterations after progression on platinum-based regimens (NCCN.org). detail...
FGFR2 mutant bladder urothelial carcinoma sensitive Erdafitinib FDA approved - Has Companion Diagnostic Actionable In a Phase II trial (BCL2001) that supported FDA approval, Balversa (erdafitinib) treatment resulted in an objective response rate of 40% (40/99, 3 complete response, 37 partial response) and a disease control rate of 80% in patients with metastatic or unresectable urothelial carcinoma harboring FGFR alterations (PMID: 31340094; NCT02365597). detail... 31340094 detail...
FGFR2 mutant cholangiocarcinoma sensitive Infigratinib Case Reports/Case Series Actionable In a Phase I trial, a patient with cholangiocarcinoma harboring an FGFR2 mutation demonstrated a decreased tumor burden when treated with Infigratinib (BGJ398) (PMID: 27870574). 27870574
FGFR2 mutant endometrial cancer sensitive PRN1371 Preclinical - Cell culture Actionable In a preclinical study, PRN1371 inhibited proliferation of endometrial cancer cells harboring FGFR2 mutations in culture (AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1249). detail...
Molecular Profile Protein Effect Treatment Approaches
FGFR2 L617M unknown
FGFR2 - SHTN1 FGFR2 E565A FGFR2 L617M
FGFR2 - SHTN1 FGFR2 L617M