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FGFR2 L618V - Gene Variant Detail

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Gene FGFR2
Variant L618V
Impact List missense
Protein Effect gain of function - predicted
Gene Variant Descriptions FGFR2 L618V (corresponds to L617V in the canonical isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). L618V has been shown to confer resistance to Fgfr inhibitors in cell culture (PMID: 28034880) and demonstrates increased Fgfr2 kinase activity compared to wild-type in an in vitro assay (PMID: 28166054), and therefore, is predicted to lead to a gain of Fgfr2 protein function.
Associated Drug Resistance Y
Category Variants Paths

FGFR2 mutant FGFR2 act mut FGFR2 L618V

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Transcript NM_001144913.1
gDNA chr10:g.121496546A>C
cDNA c.1852T>G
Protein p.L618V
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
XM_017015925.2 chr10:g.121485444G>C c.1852C>G p.L618V RefSeq GRCh38/hg38
NM_001144913.1 chr10:g.121496546A>C c.1852T>G p.L618V RefSeq GRCh38/hg38
NM_022970 chr10:g.121496546A>C c.1852T>G p.L618V RefSeq GRCh38/hg38
NM_001144913.1 chr10:g.121496546A>C c.1852T>G p.L618V RefSeq GRCh38/hg38
NM_001144913 chr10:g.121496546A>C c.1852T>G p.L618V RefSeq GRCh38/hg38
NM_022970.4 chr10:g.121496546A>C c.1852T>G p.L618V RefSeq GRCh38/hg38
XM_017015925 chr10:g.121485444G>C c.1852C>G p.L618V RefSeq GRCh38/hg38
NM_022970.3 chr10:g.121496546A>C c.1852T>G p.L618V RefSeq GRCh38/hg38
XM_017015925.3 chr10:g.121485444G>C c.1852C>G p.L618V RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
FGFR2 fusion FGFR2 L618V intrahepatic cholangiocarcinoma resistant Infigratinib Preclinical - Cell culture Actionable In a preclinical study, Truseltiq (infigratinib) treatment of intrahepatic cholangiocarcinoma cells with an FGFR2 fusion in context with FGFR2 L618V were resistant to treatment as demonstrated by cell viability and downstream signaling assays (PMID: 31109923). 31109923
FGFR2 fusion FGFR2 L618V intrahepatic cholangiocarcinoma resistant Zoligratinib Preclinical - Cell culture Actionable In a preclinical study, Debio 1347 treatment of intrahepatic cholangiocarcinoma cells with an FGFR2 fusion in context with FGFR2 L618V were resistant to treatment, as demonstrated by cell viability and downstream signaling assays (PMID: 31109923). 31109923
FGFR2 fusion FGFR2 L618V intrahepatic cholangiocarcinoma sensitive Futibatinib Preclinical - Cell culture Actionable In a preclinical study, Lytgobi (futibatinib) treatment of intrahepatic cholangiocarcinoma cells with an FGFR2 fusion in context with FGFR2 L618V were sensitive to treatment as demonstrated by decreased cell viability and decreased activation of downstream signaling (PMID: 31109923). 31109923