Variant · Snv

FGFR3 R248C

CI-VAR-00003780Explore in graph →NP_000133.1:p.Arg248CysNM_000142.4:c.742C>TClinVar 16332 CIViC 2403 rs121913482

Curated evidence

Evidence by cancer (15 items)

Grouped by cancer context first, then therapy. The same variant can be sensitizing in one cancer and irrelevant in another — contexts are never merged. 50 items per page; a cancer group may continue on the next page.

civicCuratedShowing 1–15 of 15 evidence items across 7 cancer contexts on this page · levels, directions and significance as curated at the source; each row links to its CIViC record.

Molecular profile	Therapy	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
Bladder Carcinoma3
FGFR3 R248C	(oncogenic)	Oncogenic	D	Supports Oncogenicity	2	submitted	EID10387 FGFR3 R248C promoted FGF1 and IL-3 independent cell proliferation when transduced into Ba/F3 cells whereas Ba/F3 cells with wildtype FGFR3 were IL-3 independent, but FGF1 dependent. PMID 19381019 · Qing et al., 2009 · Open in CIViC	civic
FGFR3 R248C	Infigratinib	Predictive	B	Supports Sensitivity Response	1	submitted	EID8318 Phase 2 BGJ398 dose escalation to determine maximum tolerated dose and RP2D dose. There was Antitumor activity PR in FGFR3-mutant bladder/urothelial carcinoma. PMID 27870574 · Nogova et al., 2017 · Open in CIViC	civic
FGFR3 S249C AND FGFR3 R248C AND FGFR3 Y373C AND FGFR3 G370C

ClinVar

Clinical significance (1)

ClinVar interpretations are shown as structured records — significance, review status, star rating, conditions — never flattened into one word.

clinvarCurated1 interpretation · review status and star rating as assigned by ClinVar.

Variation	Clinical significance	Review status	Stars	Conditions	Origin	Submitters	Last evaluated	Source
16332	Pathogenic	criteria provided, multiple submitters, no conflicts	2	Thanatophoric dysplasia type 1; Multiple myeloma; SKELETAL DYSPLASIA WITH ACANTHOSIS NIGRICANS; Epidermal nevus; Seborrheic keratosis; Cervical cancer; Hamartoma; FGFR3-related chondrodysplasia; Achondroplasia; Connective tissue disorder; FGFR3-related disorder; Malignant tumor of urinary bladder; Thanatophoric dysplasia, type 2; Muenke syndrome; Fetal anomalies with a likely genetic cause

Lung Squamous Cell Carcinoma1
FGFR3 R248C	(oncogenic)	Oncogenic	D	Supports Oncogenicity	3	submitted	EID7940 NIH-3T3 cells with the FGFR3 R248C extracellular domain mutation demonstrated an increase in colony formation compared to wild-type in an anchorage-independence assay, which was counteracted by treatm… (full text at CIViC) PMID 23786770 · Liao et al., 2013 · Open in CIViC	civic

Lung Squamous Cell Carcinoma1

FGFR3 R248C

(oncogenic)

Oncogenic

Supports Oncogenicity

submitted

EID7940

NIH-3T3 cells with the FGFR3 R248C extracellular domain mutation demonstrated an increase in colony formation compared to wild-type in an anchorage-independence assay, which was counteracted by treatm… (full text at CIViC)

PMID 23786770 · Liao et al., 2013 · Open in CIViC

civic

Malignant Neoplasm2
FGFR3 R248C	(oncogenic)	Oncogenic	D	Supports Oncogenicity	3	submitted	EID12841 The extracellular domain mutation R248C was tested in a series of assays for an evaluation of oncogenicity. R248C was stably transfected into 3T3 cells along with WT controls. TAS (Transformation Ac… (full text at CIViC) PMID 34272467 · Nakamura et al., 2021 · Open in CIViC	civic
FGFR3 R248C	R3Mab	Predictive	D	Does Not Support Resistance	3	accepted	EID8321 In this preclinical study, R3Mab (a monoclonal antibody specific to FGFR3) inhibited ligand-independent proliferation in Ba/F3 cells expressing common bladder carcinoma variant: FGFR3 R248C. Authors n… (full text at CIViC) PMID 19381019 · Qing et al., 2009 · Open in CIViC	civic

Malignant Neoplasm2

FGFR3 R248C

(oncogenic)

Oncogenic

Supports Oncogenicity

submitted

EID12841

The extracellular domain mutation R248C was tested in a series of assays for an evaluation of oncogenicity. R248C was stably transfected into 3T3 cells along with WT controls. TAS (Transformation Ac… (full text at CIViC)

PMID 34272467 · Nakamura et al., 2021 · Open in CIViC

civic

FGFR3 R248C

R3Mab

Predictive

Does Not Support Resistance

accepted

EID8321

In this preclinical study, R3Mab (a monoclonal antibody specific to FGFR3) inhibited ligand-independent proliferation in Ba/F3 cells expressing common bladder carcinoma variant: FGFR3 R248C. Authors n… (full text at CIViC)

PMID 19381019 · Qing et al., 2009 · Open in CIViC

civic

Squamous Cell Carcinoma1
FGFR3 R248C	(oncogenic)	Oncogenic	D	Supports Oncogenicity	3	submitted	EID8320 Expression of FGFR3 carrying the p.Arg248Cys variant in HEK293 cells resulted in increased phospho-ERK, indicating activation of the MAP Kinase pathway. Expression of FGFR3 p.Arg248Cys in a human kera… (full text at CIViC) PMID 24626198 · Duperret et al., 2014 · Open in CIViC	civic

Squamous Cell Carcinoma1

FGFR3 R248C

(oncogenic)

Oncogenic

Supports Oncogenicity

submitted

EID8320

Expression of FGFR3 carrying the p.Arg248Cys variant in HEK293 cells resulted in increased phospho-ERK, indicating activation of the MAP Kinase pathway. Expression of FGFR3 p.Arg248Cys in a human kera… (full text at CIViC)

PMID 24626198 · Duperret et al., 2014 · Open in CIViC

civic

Transitional Cell Carcinoma4
FGFR3 R248C	Dovitinib	Predictive	C	Supports Sensitivity Response	4	submitted	EID8319 Purpose of study was to assess the clinical and pharmacodynamic activity of dovitinib in a treatment resistant non-muscle invasive UC of the bladder. A multi-site pilot phase 2 trial was conducted. Ke… (full text at CIViC) PMID 27932416 · Hahn et al., 2017 · Open in CIViC	civic
FGFR3 R248C	Erdafitinib	Predictive	A	Supports Sensitivity Response	4	submitted	EID7305 Patients with metastatic or unresectable urothelial carcinoma havoring FGFR2 fusion, FGFR3 fusion or FGFR3 mutation were treated with pan-FGFR inhibitor, erdafitinib, in Phase 2 trial. 96 patients wer… (full text at CIViC) Open in CIViC	civic
FGFR3 R248C	Erdafitinib	Predictive	B	Supports Sensitivity Response	3	rejected	EID8281 The use of erdafitinib was associated with an objective tumor response in 40% of previously treated patients who had locally advanced and unresectable or metastatic urothelial carcinoma with FGFR alte… (full text at CIViC) PMID 31340094 · Loriot et al., 2019 · Open in CIViC	civic
FGFR3 R248C	Infigratinib	Predictive	B	Supports Sensitivity Response	3	submitted	EID6410 In this one-arm study, 67 patients with metastastic urothelial carcinoma and diverse FGFR3 alterations were treated with pan-FGFR Inhibitor BGJ398. The majority of patients (70.1%) had received two or… (full text at CIViC) PMID 29848605 · Pal et al., 2018 · Open in CIViC	civic

Transitional Cell Carcinoma4

FGFR3 R248C

Dovitinib

Predictive

Supports Sensitivity Response

submitted

EID8319

Purpose of study was to assess the clinical and pharmacodynamic activity of dovitinib in a treatment resistant non-muscle invasive UC of the bladder. A multi-site pilot phase 2 trial was conducted. Ke… (full text at CIViC)

PMID 27932416 · Hahn et al., 2017 · Open in CIViC

civic

FGFR3 R248C

Erdafitinib

Predictive

Supports Sensitivity Response

submitted

EID7305

Patients with metastatic or unresectable urothelial carcinoma havoring FGFR2 fusion, FGFR3 fusion or FGFR3 mutation were treated with pan-FGFR inhibitor, erdafitinib, in Phase 2 trial. 96 patients wer… (full text at CIViC)

Open in CIViC

civic

FGFR3 R248C

Erdafitinib

Predictive

Supports Sensitivity Response

rejected

EID8281

The use of erdafitinib was associated with an objective tumor response in 40% of previously treated patients who had locally advanced and unresectable or metastatic urothelial carcinoma with FGFR alte… (full text at CIViC)

PMID 31340094 · Loriot et al., 2019 · Open in CIViC

civic

FGFR3 R248C

Infigratinib

Predictive

Supports Sensitivity Response

submitted

EID6410

In this one-arm study, 67 patients with metastastic urothelial carcinoma and diverse FGFR3 alterations were treated with pan-FGFR Inhibitor BGJ398. The majority of patients (70.1%) had received two or… (full text at CIViC)

PMID 29848605 · Pal et al., 2018 · Open in CIViC

civic

Urothelial Carcinoma1
FGFR3 R248C	Erdafitinib	Predictive	A	Supports Sensitivity Response	4	submitted	EID13088 In a Phase 3 trial (NCT03390504), patients with metastatic or surgically unresectable urothelial carcinoma, who had FGFR2 or FGFR3 alterations erdafitinib was tested against chemotherapy (docetaxel or… (full text at CIViC) PMID 37870920 · Loriot et al., 2023 · Open in CIViC	civic

Urothelial Carcinoma1

FGFR3 R248C

Erdafitinib

Predictive

Supports Sensitivity Response

submitted

EID13088

In a Phase 3 trial (NCT03390504), patients with metastatic or surgically unresectable urothelial carcinoma, who had FGFR2 or FGFR3 alterations erdafitinib was tested against chemotherapy (docetaxel or… (full text at CIViC)

PMID 37870920 · Loriot et al., 2023 · Open in CIViC

civic

Unmapped disease3unmapped disease
FGFR3 R248C	(functional)	Functional	D	Supports Gain Of Function	5	accepted	EID8946 In BaF3 cells, the R248C mutant was shown to fully activate FGFR3 with complete independence of the ligand presence. Ligand independent activation was determined by proliferation, phosphorylation, and… (full text at CIViC) PMID 8640234 · Naski et al., 1996 · Open in CIViC	civic
FGFR3 R248C	(functional)	Functional	D	Supports Gain Of Function	3	submitted	EID10413 39 common nonepidermolytic, nonorganoid keratinocyte epidermal nevi were sampled from 33 patients and analyzed using a SNaPshot assay. FGFR3 R248C was found in 15/39 samples and 9/33 patients. The two… (full text at CIViC) PMID 16841094 · Hafner et al., 2006 · Open in CIViC	civic
FGFR3 R248C	(functional)	Functional	D	Does Not Support Gain Of Function	2	submitted	EID10511 Common bladder cancer and thanatophoric dysplasia type I variant FGFR3 R248C dimerization was tested in the absence of ligand via QI-FRET to determine if constitutive dimerization was leading to recep… (full text at CIViC) PMID 26244699 · Sarabipour et al., 2015 · Open in CIViC	civic

Unmapped disease3unmapped disease

FGFR3 R248C

(functional)

Functional

Supports Gain Of Function

accepted

EID8946

In BaF3 cells, the R248C mutant was shown to fully activate FGFR3 with complete independence of the ligand presence. Ligand independent activation was determined by proliferation, phosphorylation, and… (full text at CIViC)

PMID 8640234 · Naski et al., 1996 · Open in CIViC

civic

FGFR3 R248C

(functional)

Functional

Supports Gain Of Function

submitted

EID10413

39 common nonepidermolytic, nonorganoid keratinocyte epidermal nevi were sampled from 33 patients and analyzed using a SNaPshot assay. FGFR3 R248C was found in 15/39 samples and 9/33 patients. The two… (full text at CIViC)

PMID 16841094 · Hafner et al., 2006 · Open in CIViC

civic

FGFR3 R248C

(functional)

Functional

Does Not Support Gain Of Function

submitted

EID10511

Common bladder cancer and thanatophoric dysplasia type I variant FGFR3 R248C dimerization was tested in the absence of ligand via QI-FRET to determine if constitutive dimerization was leading to recep… (full text at CIViC)

PMID 26244699 · Sarabipour et al., 2015 · Open in CIViC

civic