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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_000142.5 |
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_047449822.1 | chr4:g.1801837C>T | c.742C>T | p.R248C | RefSeq | GRCh38/hg38 |
XM_047449824.1 | 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 |
NM_001354810.1 | 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 |
XM_011513420.2 | chr4:g.1801837C>T | c.742C>T | p.R248C | RefSeq | GRCh38/hg38 |
XM_011513422.2 | 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 |
XM_006713869.1 | chr4:g.1801837C>T | c.742C>T | p.R248C | RefSeq | GRCh38/hg38 |
XM_006713870.1 | 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_011513420 | 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 |
NM_000142.5 | 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 |
XM_006713873.2 | chr4:g.1801837C>T | c.742C>T | p.R248C | RefSeq | GRCh38/hg38 |
XM_047449821.1 | chr4:g.1801837C>T | c.742C>T | p.R248C | RefSeq | GRCh38/hg38 |
XM_047449823.1 | 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_006713869 | chr4:g.1801837C>T | c.742C>T | p.R248C | RefSeq | GRCh38/hg38 |
NM_001354809.2 | 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 |
NM_001354809.1 | chr4:g.1801837C>T | c.742C>T | p.R248C | RefSeq | GRCh38/hg38 |
XM_006713868.2 | 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 |
NM_022965.4 | 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_047449820.1 | chr4:g.1801837C>T | c.742C>T | p.R248C | RefSeq | GRCh38/hg38 |
XM_006713870.2 | 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_006713869.2 | 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 |
XM_006713871.2 | 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 |
XM_006713873 | 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 |
XM_006713872 | chr4:g.1801837C>T | c.742C>T | p.R248C | RefSeq | GRCh38/hg38 |
NM_001354810.2 | 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_001163213.2 | 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 | 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 R248C (PMID: 38490358; ESMO.org). | 38490358 detail... |
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 | 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 R248C | 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 R248C (PMID: 38490358; ESMO.org). | 38490358 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... |
FGFR3 R248C | transitional cell carcinoma | sensitive | Dasatinib + PD173074 | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of Sprycel (dasatinib) to treatment with PD173074 enhanced inhibition of colony formation of a urothelial cancer cell line harboring FGFR3 R248C in culture (PMID: 32370101). | 32370101 |
FGFR3 R248C | transitional cell carcinoma | sensitive | Dasatinib + Infigratinib | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of Sprycel (dasatinib) to treatment with Truseltiq (infigratinib) enhanced inhibition of colony formation and synergistically decreased viability in a urothelial cancer cell line harboring FGFR3 R248C in culture (PMID: 32370101). | 32370101 |
FGFR3 R248C | breast cancer | predicted - sensitive | Erdafitinib | Case Reports/Case Series | Actionable | In a Phase II trial (RAGNAR), treatment with Balversa (erdafitinib) resulted in a partial response with a duration of response of 12.75 months in a patient with breast cancer harboring FGFR3 R248C (PMID: 37541273; NCT04083976). | 37541273 |
FGFR3 R248C | 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 |