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Gene | FGFR1 |
Variant | N193fs |
Impact List | frameshift |
Protein Effect | loss of function - predicted |
Gene Variant Descriptions | FGFR1 N193fs results in a change in the amino acid sequence of the Fgfr1 protein beginning at aa 193 of 822, likely resulting in premature truncation of the functional protein (UniProt.org). N193fs results in decreased proliferation relative to wild-type Fgfr1 in a competition assay and decreased transformation activity in cultured cells (PMID: 34272467), and therefore, is predicted to lead to a loss of Fgfr1 protein function. |
Associated Drug Resistance | |
Category Variants Paths |
FGFR1 mutant FGFR1 inact mut FGFR1 N193fs |
Transcript | NM_023110.3 |
gDNA | chr8:g.(38427965_38427966) |
cDNA | c.(577_576) |
Protein | p.N193fs |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_001174063.1 | chr8:g.(38427965_38427966) | c.(577_576) | p.N193fs | RefSeq | GRCh38/hg38 |
XM_006716303.3 | chr8:g.(38427965_38427966) | c.(577_576) | p.N193fs | RefSeq | GRCh38/hg38 |
XM_047421570.1 | chr8:g.(38427965_38427966) | c.(577_576) | p.N193fs | RefSeq | GRCh38/hg38 |
XM_017013221.1 | chr8:g.(38427965_38427966) | c.(577_576) | p.N193fs | RefSeq | GRCh38/hg38 |
NM_001174063.2 | chr8:g.(38427965_38427966) | c.(577_576) | p.N193fs | RefSeq | GRCh38/hg38 |
XM_006716304.2 | chr8:g.(38427965_38427966) | c.(577_576) | p.N193fs | RefSeq | GRCh38/hg38 |
XM_017013221.2 | chr8:g.(38427965_38427966) | c.(577_576) | p.N193fs | RefSeq | GRCh38/hg38 |
XM_017013222.2 | chr8:g.(38427965_38427966) | c.(577_576) | p.N193fs | RefSeq | GRCh38/hg38 |
XM_006716304.1 | chr8:g.(38427965_38427966) | c.(577_576) | p.N193fs | RefSeq | GRCh38/hg38 |
NM_023110.3 | chr8:g.(38427965_38427966) | c.(577_576) | p.N193fs | RefSeq | GRCh38/hg38 |
NM_023110.2 | chr8:g.(38427965_38427966) | c.(577_576) | p.N193fs | RefSeq | GRCh38/hg38 |
XM_006716303.4 | chr8:g.(38427965_38427966) | c.(577_576) | p.N193fs | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
FGFR1 mutant | Advanced Solid Tumor | predicted - sensitive | ICP-192 | Phase I | Actionable | In a Phase I trial, ICP-192 (gunagratinib) was well-tolerated, and resulted in an overall response rate or 33.3% (4/12, 1 complete response, 3 partial response) and a disease control rate of 91.7% (11/12) in patients with advanced solid tumors harboring FGF/FGFR gene aberrations (J Clin Oncol 39, 2021 (suppl 15; abstr 4092); NCT03758664). | detail... |
FGFR1 mutant | Advanced Solid Tumor | predicted - sensitive | Erdafitinib | Case Reports/Case Series | Actionable | In a Phase II trial (MATCH), Balversa (erdafitinib) treatment resulted in an objective response rate of 16% (4/25), median progression-free survival of 3.6 months, and median overall survival of 11.0 months in patients with advanced solid tumors harboring FGFR1, FGFR2, or FGFR3 mutations or fusions (PMID: 38603650; NCT02465060). | 38603650 |
FGFR1 mutant | Advanced Solid Tumor | predicted - sensitive | Zoligratinib | 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 |
FGFR1 mutant | transitional cell carcinoma | predicted - sensitive | Erdafitinib | Phase II | Actionable | In a Phase II trial, Balversa (erdafitinib) treatment resulted in an objective response rate of 42% (40/96, 3 complete response, 37 partial response) and a disease control rate of 80% in patients with metastatic or unresectable urothelial carcinoma harboring FGFR alterations (J Clin Oncol 36, 2018 (suppl; abstr 4503); NCT02365597). | detail... |
FGFR1 mutant | Advanced Solid Tumor | sensitive | Pemigatinib | Preclinical - Cell line xenograft | 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... |