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Gene | FGFR3 |
Variant | R248C |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | FGFR3 R248C lies within the extracellular domain of the Fgfr3 protein (UniProt.org). R248C confers a gain of function to the Fgfr3 protein as demonstrated by constitutive ligand-independent cell proliferation (PMID: 19381019) and increased activation of the Mapk signaling pathway (PMID: 24626198). |
Associated Drug Resistance | |
Category Variants Paths |
FGFR3 mutant FGFR3 act mut FGFR3 R248C |
Transcript | NM_000142.4 |
gDNA | chr4:g.1801837C>T |
cDNA | c.742C>T |
Protein | p.R248C |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
XM_006713870.1 | chr4:g.1801837C>T | c.742C>T | p.R248C | RefSeq | GRCh38/hg38 |
XM_011513420 | chr4:g.1801837C>T | c.742C>T | p.R248C | RefSeq | GRCh38/hg38 |
XM_006713871 | chr4:g.1801837C>T | c.742C>T | p.R248C | RefSeq | GRCh38/hg38 |
NM_000142.4 | chr4:g.1801837C>T | c.742C>T | p.R248C | RefSeq | GRCh38/hg38 |
NM_022965.3 | chr4:g.1801837C>T | c.742C>T | p.R248C | RefSeq | GRCh38/hg38 |
XM_006713868 | chr4:g.1801837C>T | c.742C>T | p.R248C | RefSeq | GRCh38/hg38 |
XM_006713872 | chr4:g.1801837C>T | c.742C>T | p.R248C | RefSeq | GRCh38/hg38 |
XM_006713873 | chr4:g.1801837C>T | c.742C>T | p.R248C | RefSeq | GRCh38/hg38 |
NM_001354810.1 | chr4:g.1801837C>T | c.742C>T | p.R248C | RefSeq | GRCh38/hg38 |
XM_006713873.1 | chr4:g.1801837C>T | c.742C>T | p.R248C | RefSeq | GRCh38/hg38 |
XM_011513420.1 | chr4:g.1801837C>T | c.742C>T | p.R248C | RefSeq | GRCh38/hg38 |
XM_011513422 | chr4:g.1801837C>T | c.742C>T | p.R248C | RefSeq | GRCh38/hg38 |
NM_022965 | chr4:g.1801837C>T | c.742C>T | p.R248C | RefSeq | GRCh38/hg38 |
NM_001354809.1 | chr4:g.1801837C>T | c.742C>T | p.R248C | RefSeq | GRCh38/hg38 |
NM_000142 | chr4:g.1801837C>T | c.742C>T | p.R248C | RefSeq | GRCh38/hg38 |
NM_001163213.1 | chr4:g.1801837C>T | c.742C>T | p.R248C | RefSeq | GRCh38/hg38 |
XM_006713870 | chr4:g.1801837C>T | c.742C>T | p.R248C | RefSeq | GRCh38/hg38 |
XM_006713869.1 | chr4:g.1801837C>T | c.742C>T | p.R248C | RefSeq | GRCh38/hg38 |
XM_011513422.1 | chr4:g.1801837C>T | c.742C>T | p.R248C | RefSeq | GRCh38/hg38 |
XM_006713868.1 | chr4:g.1801837C>T | c.742C>T | p.R248C | RefSeq | GRCh38/hg38 |
XM_006713869 | chr4:g.1801837C>T | c.742C>T | p.R248C | RefSeq | GRCh38/hg38 |
XM_006713871.1 | chr4:g.1801837C>T | c.742C>T | p.R248C | RefSeq | GRCh38/hg38 |
NM_001163213 | chr4:g.1801837C>T | c.742C>T | p.R248C | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
FGFR3 R248C | Advanced Solid Tumor | sensitive | Vofatamab | Preclinical - Cell culture | Actionable | In a preclinical study, Vofatamab (B-701) inhibited ligand-independent proliferation induced by FGFR3 R248C in cultured cells (PMID: 19381019). | 19381019 |
FGFR3 R248C | Advanced Solid Tumor | sensitive | Infigratinib | Preclinical - Cell culture | Actionable | In a preclinical study, Truseltiq (infigratinib) inhibited growth of transformed cells expressing FGFR3 R248C in culture (PMID: 23786770). | 23786770 |
FGFR3 R248C | Advanced Solid Tumor | conflicting | Dovitinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing FGFR3 R248C were resistant to treatment with Dovitinib (TKI258) in culture (PMID: 34272467). | 34272467 |
FGFR3 R248C | Advanced Solid Tumor | conflicting | Dovitinib | Preclinical - Cell culture | Actionable | In a preclinical study, Dovitinib (TKI258) inhibited growth of transformed cells expressing FGFR3 R248C in culture (PMID: 23786770). | 23786770 |
FGFR3 R248C | Advanced Solid Tumor | sensitive | Pazopanib | Preclinical - Cell culture | Actionable | In a preclinical study, Votrient (pazopanib) inhibited growth of transformed cells expressing FGFR3 R248C in culture (PMID: 23786770). | 23786770 |
FGFR3 R248C | 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 R248C is included in the companion diagnostic (PMID: 31340094; NCT02365597). | 31340094 detail... detail... |
FGFR3 R248C | 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 R248C is included in the companion diagnostic (PMID: 31340094; NCT02365597). | detail... 31340094 detail... |