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FGFR1 K656E - Gene Variant Detail

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Gene FGFR1
Variant K656E
Impact List missense
Protein Effect gain of function
Gene Variant Descriptions FGFR1 K656E lies within the protein kinase domain of the Fgfr1 protein (UniProt.org). K656E does not confer a growth advantage in a competition assay but confers a gain of function to the Fgfr1 protein as demonstrated by constitutive activation of MAPK signaling (PMID: 23817572), and is transforming in cultured cells (PMID: 23817572, PMID: 34272467).
Associated Drug Resistance
Category Variants Paths

FGFR1 mutant FGFR1 act mut FGFR1 K656E

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Transcript NM_023110.3
gDNA chr8:g.38414790T>C
cDNA c.1966A>G
Protein p.K656E
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
XM_011544450 chr8:g.38414198T>C c.1966A>G p.K656E RefSeq GRCh38/hg38
XM_006716303.4 chr8:g.38414790T>C c.1966A>G p.K656E RefSeq GRCh38/hg38
XM_017013221 chr8:g.38414790T>C c.1966A>G p.K656E RefSeq GRCh38/hg38
XM_017013226.1 chr8:g.38414198T>C c.1966A>G p.K656E RefSeq GRCh38/hg38
XM_006716304.1 chr8:g.38414790T>C c.1966A>G p.K656E RefSeq GRCh38/hg38
XM_017013226.2 chr8:g.38414198T>C c.1966A>G p.K656E RefSeq GRCh38/hg38
XM_006716303.3 chr8:g.38414790T>C c.1966A>G p.K656E RefSeq GRCh38/hg38
XM_011544450.2 chr8:g.38414198T>C c.1966A>G p.K656E RefSeq GRCh38/hg38
XM_011544449.1 chr8:g.38414198T>C c.1966A>G p.K656E RefSeq GRCh38/hg38
XM_011544449.2 chr8:g.38414198T>C c.1966A>G p.K656E RefSeq GRCh38/hg38
XM_017013221.2 chr8:g.38414790T>C c.1966A>G p.K656E RefSeq GRCh38/hg38
XM_011544450.3 chr8:g.38414198T>C c.1966A>G p.K656E RefSeq GRCh38/hg38
XM_006716304 chr8:g.38414790T>C c.1966A>G p.K656E RefSeq GRCh38/hg38
XM_047421575.1 chr8:g.38415857T>C c.1966A>G p.K656E RefSeq GRCh38/hg38
NM_023110 chr8:g.38414790T>C c.1966A>G p.K656E RefSeq GRCh38/hg38
XM_011544449 chr8:g.38414198T>C c.1966A>G p.K656E RefSeq GRCh38/hg38
NM_023110.3 chr8:g.38414790T>C c.1966A>G p.K656E RefSeq GRCh38/hg38
XM_006716304.2 chr8:g.38414790T>C c.1966A>G p.K656E RefSeq GRCh38/hg38
XM_017013226 chr8:g.38414198T>C c.1966A>G p.K656E RefSeq GRCh38/hg38
NM_023110.2 chr8:g.38414790T>C c.1966A>G p.K656E RefSeq GRCh38/hg38
XM_017013221.1 chr8:g.38414790T>C c.1966A>G p.K656E RefSeq GRCh38/hg38
XM_006716303 chr8:g.38414790T>C c.1966A>G p.K656E RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
FGFR1 K656E Advanced Solid Tumor predicted - resistant Dovitinib Preclinical - Cell culture Actionable In a preclinical study, cells expressing FGFR1 K656E were resistant to treatment with Dovitinib (TKI258) in culture (PMID: 34272467). 34272467
FGFR1 K656E Advanced Solid Tumor conflicting Pemigatinib Preclinical - Cell culture Actionable In a preclinical study, cells expressing FGFR1 K656E demonstrated insensitivity to Pemazyre (pemigatinib) in culture (PMID: 34114373). 34114373
FGFR1 K656E Advanced Solid Tumor conflicting Pemigatinib Preclinical - Cell culture Actionable In a preclinical study, cells expressing FGFR1 K656E were sensitive to treatment with Pemazyre (pemigatinib) in culture, demonstrating reduced cell viability (PMID: 34272467). 34272467
FGFR1 K656E Advanced Solid Tumor conflicting Erdafitinib Preclinical - Cell culture Actionable In a preclinical study, cells expressing FGFR1 K656E demonstrated insensitivity to Balversa (erdafitinib) in culture (PMID: 34114373). 34114373
FGFR1 K656E Advanced Solid Tumor conflicting Erdafitinib Preclinical - Cell culture Actionable In a preclinical study, cells expressing FGFR1 K656E were sensitive to treatment with Balversa (erdafitinib) in culture, demonstrating reduced cell viability (PMID: 34272467). 34272467
FGFR1 K656E Advanced Solid Tumor conflicting Infigratinib Preclinical - Cell culture Actionable In a preclinical study, cells expressing FGFR1 K656E demonstrated insensitivity to Truseltiq (infigratinib) in culture (PMID: 34114373). 34114373
FGFR1 K656E Advanced Solid Tumor conflicting Infigratinib Preclinical - Cell culture Actionable In a preclinical study, cells expressing FGFR1 K656E were sensitive to treatment with Truseltiq (infigratinib) in culture, demonstrating reduced cell viability (PMID: 34272467). 34272467
FGFR1 K656E Advanced Solid Tumor predicted - sensitive Olverembatinib Preclinical - Cell culture Actionable In a preclinical study, Olverembatinib (HQP1351) inhibited growth of a cell line expressing FGFR1 K656E in culture (PMID: 34114373). 34114373
FGFR1 K656E Advanced Solid Tumor predicted - sensitive Futibatinib Preclinical - Cell culture Actionable In a preclinical study, Lytgobi (futibatinib) inhibited growth of a cell line expressing FGFR1 K656E in culture (PMID: 34114373). 34114373
FGFR1 K656E high grade glioma predicted - sensitive Infigratinib Case Reports/Case Series Actionable In a Phase II trial, Truseltiq (infigratinib) treatment resulted in limited efficacy with a 6-month progression-free survival (PFS) rate of 16.0%, a median PFS of 1.7 months, an objective response rate of 4.8% (1/21), and median overall survival of 6.7 months in patients with recurrent glioma harboring alterations in FGFR1 or FGFR3; however, resulted in a partial response with PFS of 21.9 months and stable disease with PFS of 13.2 months in two patients harboring FGFR1 K656E (PMID: 35344029; NCT01975701). 35344029
FGFR1 K656E diffuse astrocytoma predicted - sensitive Pemigatinib Case Reports/Case Series Actionable In a Phase II trial (FIGHT-207), Pemazyre (pemigatinib) treatment demonstrated safety in previously treated patients with advanced solid tumors harboring a kinase domain mutation or a variant of unknown significance in FGFR1, FGFR2, or FGFR3, and resulted in an objective response rate of 3.8% (1/26, partial responses), including a partial response with a progression-free survival of 8.0 months in a patient with diffuse astrocytoma harboring FGFR1 K656E (PMID: 38710951; NCT03822117). 38710951
FGFR1 K656E low grade glioma predicted - sensitive Erdafitinib Case Reports/Case Series Actionable In a Phase II trial (RAGNAR), treatment with Balversa (erdafitinib) resulted in a complete response with a duration of response of 21.68 months in a patient with low grade glioma harboring FGFR1 K656E (PMID: 37541273; NCT04083976). 37541273