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Gene | FGFR3 |
Variant | G370C |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | FGFR3 G370C lies within the juxtamembrane region of the Fgfr3 protein (PMID: 12009017). G370C confers a gain of function to the Fgfr3 protein as demonstrated by increased Fgfr3 phosphorylation, constitutive activation of the Mapk signaling pathway (PMID: 12009017), a growth advantage relative to wild-type Fgfr3 in a competition assay, and increased transformation activity in cultured cells (PMID: 34272467). |
Associated Drug Resistance | |
Category Variants Paths |
FGFR3 mutant FGFR3 act mut FGFR3 G370C |
Transcript | NM_000142.5 |
gDNA | chr4:g.1804362G>T |
cDNA | c.1108G>T |
Protein | p.G370C |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_001354809.1 | chr4:g.1804362G>T | c.1108G>T | p.G370C | RefSeq | GRCh38/hg38 |
NM_000142.4 | chr4:g.1804362G>T | c.1108G>T | p.G370C | RefSeq | GRCh38/hg38 |
XM_047449823.1 | chr4:g.1804362G>T | c.1108G>T | p.G370C | RefSeq | GRCh38/hg38 |
XM_006713873.1 | chr4:g.1804362G>T | c.1108G>T | p.G370C | RefSeq | GRCh38/hg38 |
XM_006713873.2 | chr4:g.1804362G>T | c.1108G>T | p.G370C | RefSeq | GRCh38/hg38 |
NM_000142 | chr4:g.1804362G>T | c.1108G>T | p.G370C | RefSeq | GRCh38/hg38 |
NM_001354810.2 | chr4:g.1804362G>T | c.1108G>T | p.G370C | RefSeq | GRCh38/hg38 |
XM_011513422.2 | chr4:g.1804362G>T | c.1108G>T | p.G370C | RefSeq | GRCh38/hg38 |
NM_000142.5 | chr4:g.1804362G>T | c.1108G>T | p.G370C | RefSeq | GRCh38/hg38 |
XM_011513422.1 | chr4:g.1804362G>T | c.1108G>T | p.G370C | RefSeq | GRCh38/hg38 |
NM_001354810.1 | chr4:g.1804362G>T | c.1108G>T | p.G370C | RefSeq | GRCh38/hg38 |
XM_006713873 | chr4:g.1804362G>T | c.1108G>T | p.G370C | RefSeq | GRCh38/hg38 |
XM_011513420.1 | chr4:g.1804362G>T | c.1108G>T | p.G370C | RefSeq | GRCh38/hg38 |
XM_011513420.2 | chr4:g.1804362G>T | c.1108G>T | p.G370C | RefSeq | GRCh38/hg38 |
XM_047449824.1 | chr4:g.1804362G>T | c.1108G>T | p.G370C | RefSeq | GRCh38/hg38 |
XM_006713872 | chr4:g.1804362G>T | c.1108G>T | p.G370C | RefSeq | GRCh38/hg38 |
XM_011513422 | chr4:g.1804362G>T | c.1108G>T | p.G370C | RefSeq | GRCh38/hg38 |
XM_047449822.1 | chr4:g.1804362G>T | c.1108G>T | p.G370C | RefSeq | GRCh38/hg38 |
NM_001354809.2 | chr4:g.1804362G>T | c.1108G>T | p.G370C | RefSeq | GRCh38/hg38 |
XM_011513420 | chr4:g.1804362G>T | c.1108G>T | p.G370C | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
FGFR3 G370C | Advanced Solid Tumor | predicted - sensitive | Infigratinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing FGFR3 G370C were sensitive to treatment with Truseltiq (infigratinib) in culture, demonstrating reduced cell viability (PMID: 34272467). | 34272467 |
FGFR3 G370C | Advanced Solid Tumor | predicted - resistant | Dovitinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing FGFR3 G370C were resistant to treatment with Dovitinib (TKI258) in culture (PMID: 34272467). | 34272467 |
FGFR3 G370C | transitional cell carcinoma | sensitive | Erdafitinib | Guideline | Actionable | Balversa (erdafitinib) is included in guidelines for patients with advanced urothelial carcinoma who have received chemotherapy and an immune checkpoint inhibitor and harboring select FGFR mutations including FGFR3 G370C (PMID: 38490358; ESMO.org). | 38490358 detail... |
FGFR3 G370C | transitional cell carcinoma | sensitive | Erdafitinib | FDA approved - On Companion Diagnostic | Actionable | In a Phase II trial (BCL2001) that supported FDA approval, Balversa (erdafitinib) treatment resulted in an objective response rate of 40% (40/99, 3 complete response, 37 partial response) and a disease control rate of 80% in patients with metastatic or unresectable urothelial carcinoma harboring FGFR alterations and FGFR3 G370C is included in the companion diagnostic (PMID: 31340094; NCT02365597). | detail... 31340094 detail... |
FGFR3 G370C | transitional cell carcinoma | sensitive | Erdafitinib | Case Reports/Case Series | Actionable | In a Phase III trial (THOR), Balversa (erdafitinib) treatment led to improved median overall survival (25.4 mo vs. 12.4 mo), median progression-free survival (8.4 mo vs. 2.9 mo), objective response rate (57.1% vs. 15.4%), and disease control rate (92.9% vs. 76.9%) compared to chemotherapy in Japanese patients with metastatic urothelial carcinoma with alterations in FGFR2 or FGFR3 (n=14), including FGFR3 Y373C (n=3), S249C (n=4), G370C (n=2), R248C (n=2), and FGFR3-TACC3 (n=3) (PMID: 39017806; NCT03390504). | 39017806 |
FGFR3 G370C | bladder urothelial carcinoma | sensitive | Erdafitinib | Guideline | Actionable | Balversa (erdafitinib) is included in guidelines for patients with advanced bladder urothelial carcinoma who have received chemotherapy and an immune checkpoint inhibitor and harboring select FGFR mutations including FGFR3 G370C (PMID: 38490358; ESMO.org). | 38490358 detail... |
FGFR3 G370C | bladder urothelial carcinoma | sensitive | Erdafitinib | FDA approved - On Companion Diagnostic | Actionable | In a Phase II trial (BCL2001) that supported FDA approval, Balversa (erdafitinib) treatment resulted in an objective response rate of 40% (40/99, 3 complete response, 37 partial response) and a disease control rate of 80% in patients with metastatic or unresectable urothelial carcinoma harboring FGFR alterations and FGFR3 G370C is included in the companion diagnostic (PMID: 31340094; NCT02365597). | detail... 31340094 detail... |
FGFR3 G370C | urinary bladder cancer | predicted - sensitive | Erdafitinib | Case Reports/Case Series | Actionable | In a Phase II trial (THOR-2), Balversa (erdafitinib) improved median recurrence-free survival (not reached vs 11.6 mo, HR=0.28, p=0.0008) in patients with recurrent high risk non-muscle invasive bladder cancer harboring FGFR3 mutations such as S249C (n=31), R248C (n=4), G370C, (n=3) or Y373C (n=10) or FGFR2-BICC1 (n=1), FGFR3-BAIAP2L1 (n=1), or FGFR3-TACC3 (n=5) compared to intravesical chemotherapy (PMID: 37871701; NCT04172675). | 37871701 |
FGFR3 G370C | Advanced Solid Tumor | predicted - resistant | E7090 | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing FGFR3 G370C were resistant to treatment with E7090 in culture (PMID: 34272467). | 34272467 |