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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 |
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 |
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 |