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Gene | FGFR2 |
Variant | L617V |
Impact List | missense |
Protein Effect | gain of function - predicted |
Gene Variant Descriptions | FGFR2 L617V (also referred to as V618V from the FGFR2IIIb isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). L617V 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 vitro (PMID: 28166054), and therefore, is predicted to result in a gain of Fgfr2 protein function. |
Associated Drug Resistance | Y |
Transcript | NM_000141.4 |
gDNA | chr10:g.121496546A>C |
cDNA | c.1849T>G |
Protein | p.L617V |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
XM_017015925 | chr10:g.121485447G>C | c.1849C>G | p.L617V | RefSeq | GRCh38/hg38 |
NM_000141.4 | chr10:g.121496546A>C | c.1849T>G | p.L617V | RefSeq | GRCh38/hg38 |
NM_001144916 | chr10:g.121485396G>C | c.1849C>G | p.L617V | RefSeq | GRCh38/hg38 |
NM_001144916.1 | chr10:g.121485396G>C | c.1849C>G | p.L617V | RefSeq | GRCh38/hg38 |
NM_000141 | chr10:g.121496546A>C | c.1849T>G | p.L617V | RefSeq | GRCh38/hg38 |
XM_006717712 | chr10:g.121485456G>C | c.1849C>G | p.L617V | RefSeq | GRCh38/hg38 |
XM_017015925.2 | chr10:g.121485447G>C | c.1849C>G | p.L617V | RefSeq | GRCh38/hg38 |
XM_024447891.1 | chr10:g.121485456G>C | c.1849C>G | p.L617V | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
FGFR2 - OPTN FGFR2 N549H FGFR2 V564F FGFR2 E565A FGFR2 L617V FGFR2 K641R | cholangiocarcinoma | predicted - resistant | Infigratinib | Case Reports/Case Series | Actionable | In a clinical case study, FGFR2 mutations E565A, K641R, L617V, N549H and V564F were identified in the cell-free DNA of a cholangiocarcinoma patient harboring FGFR2-OPTN fusion after the patient progressed while on Truseltiq (infigratinib) treatment (PMID: 28034880). | 28034880 |
FGFR2 - AHCYL1 FGFR2 L617V | cholangiocarcinoma | predicted - resistant | Pemigatinib | Case Reports/Case Series | Actionable | In a Phase II trial (FIGHT-202), a cholangiocarcinoma patient harboring FGFR2-AHCYL1 experienced disease progression after 6.8 months of treatment with Pemazyre (pemigatinib), and was found to have acquired FGFR2 L617V (PMID: 33218975; NCT02924376). | 33218975 |
FGFR2 - TRIM8 FGFR2 E565A FGFR2 L617V FGFR2 K659M | cholangiocarcinoma | predicted - resistant | Pemigatinib | Case Reports/Case Series | Actionable | In a Phase II trial (FIGHT-202), a cholangiocarcinoma patient harboring FGFR2-TRIM8 experienced disease progression after 9.1 months of treatment with Pemazyre (pemigatinib), and was found to have acquired FGFR2 E565A, FGFR2 L617V, and FGFR2 K659M (PMID: 33218975; NCT02924376). | 33218975 |
FGFR2 - KIAA1217 FGFR2 N549D FGFR2 N549H FGFR2 N549K FGFR2 V564F FGFR2 V564I FGFR2 V564L FGFR2 E565A FGFR2 L617F FGFR2 L617V FGFR2 K659M FGFR2 Q746L | cholangiocarcinoma | predicted - resistant | Infigratinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with cholangiocarcinoma harboring an FGFR2-KIAA1217 fusion experienced disease progression after 10.6 months of treatment with Truseltiq (infigratinib) and was found to have acquired additional FGFR2 mutations, N549K, N549D, N549H, V564F, V564I, V564L, E565A, L617V, L617F, K659M, Q746L (PMID: 34250419). | 34250419 |
Molecular Profile | Protein Effect | Treatment Approaches |
---|---|---|
FGFR2 L617V | gain of function - predicted | FGFR Inhibitor (Pan) FGFR2 Inhibitor |
FGFR2 - OPTN FGFR2 N549H FGFR2 V564F FGFR2 E565A FGFR2 L617V FGFR2 K641R | ||
FGFR2 - AHCYL1 FGFR2 L617V | ||
FGFR2 - TRIM8 FGFR2 E565A FGFR2 L617V FGFR2 K659M | ||
FGFR2 - KIAA1217 FGFR2 N549D FGFR2 N549H FGFR2 N549K FGFR2 V564F FGFR2 V564I FGFR2 V564L FGFR2 E565A FGFR2 L617F FGFR2 L617V FGFR2 K659M FGFR2 Q746L |