FGFR3 Y373C

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Molecular profile	Therapy	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
Bladder Carcinoma2
FGFR3 S249C AND FGFR3 R248C AND FGFR3 Y373C AND FGFR3 G370C	Erdafitinib	Predictive	A	Supports Sensitivity Response	4	rejected	EID11259 In this open-label, phase II trial, 99 patients with locally advanced and unresectable or metastatic urothelial carcinoma with various FGFR alterations who had a history of disease progression during … (full text at CIViC) PMID 31340094 · Loriot et al., 2019 · Open in CIViC	civic
FGFR3 Y373C	(diagnostic)	Diagnostic	B	Supports Positive	3	accepted	EID477 Y375C mutation results in activation of FGFR3 and is associated with bladder carcinoma. Patients with low-grade tumors were more likely to have FGFR3 mutations than those with high-grade tumors. PMID 20542753 · Bodoor et al., 2010 · Open in CIViC	civic

Molecular profile

Therapy

Type

Level

Direction · significance

Rating (1–5)

Status

Evidence

Source

Bladder Carcinoma2

FGFR3 S249C AND FGFR3 R248C AND FGFR3 Y373C AND FGFR3 G370C

Erdafitinib

Predictive

Supports Sensitivity Response

rejected

EID11259

In this open-label, phase II trial, 99 patients with locally advanced and unresectable or metastatic urothelial carcinoma with various FGFR alterations who had a history of disease progression during … (full text at CIViC)

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

civic

FGFR3 Y373C

(diagnostic)

Diagnostic

Supports Positive

accepted

EID477

Y375C mutation results in activation of FGFR3 and is associated with bladder carcinoma. Patients with low-grade tumors were more likely to have FGFR3 mutations than those with high-grade tumors.

PMID 20542753 · Bodoor et al., 2010 · Open in CIViC

civic

Variation	Clinical significance	Review status	Stars	Conditions	Origin	Submitters	Last evaluated	Source
16342	Pathogenic	criteria provided, multiple submitters, no conflicts	2	Thanatophoric dysplasia type 1; FGFR3-related disorder; Achondroplasia; Neoplasm; FGFR3-related chondrodysplasia	germline/somatic	27	Jun 23, 2026	clinvar

Variation

Clinical significance

Review status

Stars

Conditions

Origin

Submitters

Last evaluated

Source

16342

Pathogenic

criteria provided, multiple submitters, no conflicts

Thanatophoric dysplasia type 1; FGFR3-related disorder; Achondroplasia; Neoplasm; FGFR3-related chondrodysplasia

germline/somatic

Jun 23, 2026

clinvar

Malignant Neoplasm4
FGFR3 Y373C	(oncogenic)	Oncogenic	D	Supports Oncogenicity	3	submitted	EID8883 Transfection with constructs expressing FGFR3 Y373C induced transformation of NIH3T3 cells in a colony formation assay, while wild type FGFR3 did not. PMID 11157491 · Chesi et al., 2001 · Open in CIViC	civic
FGFR3 Y373C	(oncogenic)	Oncogenic	D	Supports Oncogenicity	3	submitted	EID8884 The FGFR3 Y373C variant is present in the KMS-11multiple myeloma cell line, on the background of a 4;14 translocation. This cell line shows ligand independent phosphorylation of FGFR3, in contrast to … (full text at CIViC) PMID 11429702 · Ronchetti et al., 2001 · Open in CIViC	civic
FGFR3 Y373C	(oncogenic)	Oncogenic	D	Supports Oncogenicity	3	accepted	EID12844 The extracellular/transmembrane domain mutation Y373C was tested in a series of assays for an evaluation of oncogenicity. Y373C was stably transfected into 3T3 cells along with WT controls. TAS (Tra… (full text at CIViC) PMID 34272467 · Nakamura et al., 2021 · Open in CIViC	civic
FGFR3 Y373C	R3Mab	Predictive	D	Does Not Support Resistance	3	accepted	EID10354 Pro-B Ba/F3 cells transfected with wild type FGFR3 resulted in IL-3 independence with FGF1 dependence for growth. Cell transfected FGFR3 with mutation Y375C also resulted in IL-3 independence and FGF1… (full text at CIViC) PMID 19381019 · Qing et al., 2009 · Open in CIViC	civic

Malignant Neoplasm4

FGFR3 Y373C

(oncogenic)

Oncogenic

Supports Oncogenicity

submitted

EID8883

Transfection with constructs expressing FGFR3 Y373C induced transformation of NIH3T3 cells in a colony formation assay, while wild type FGFR3 did not.

PMID 11157491 · Chesi et al., 2001 · Open in CIViC

civic

FGFR3 Y373C

(oncogenic)

Oncogenic

Supports Oncogenicity

submitted

EID8884

The FGFR3 Y373C variant is present in the KMS-11multiple myeloma cell line, on the background of a 4;14 translocation. This cell line shows ligand independent phosphorylation of FGFR3, in contrast to … (full text at CIViC)

PMID 11429702 · Ronchetti et al., 2001 · Open in CIViC

civic

FGFR3 Y373C

(oncogenic)

Oncogenic

Supports Oncogenicity

accepted

EID12844

The extracellular/transmembrane domain mutation Y373C was tested in a series of assays for an evaluation of oncogenicity. Y373C was stably transfected into 3T3 cells along with WT controls. TAS (Tra… (full text at CIViC)

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

civic

FGFR3 Y373C

R3Mab

Predictive

Does Not Support Resistance

accepted

EID10354

Pro-B Ba/F3 cells transfected with wild type FGFR3 resulted in IL-3 independence with FGF1 dependence for growth. Cell transfected FGFR3 with mutation Y375C also resulted in IL-3 independence and FGF1… (full text at CIViC)

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

civic

Multiple Myeloma3
FGFR3 Y373C	(oncogenic)	Oncogenic	D	Supports Oncogenicity	2	submitted	EID10385 Ba/F3 cells transfected with wild type FGFR3 or common bladder carcinoma variant FGFR3 Y375C both resulted in IL-3 independence with FGF1 dependence for growth. However, tumors grew when multiple myel… (full text at CIViC) PMID 19381019 · Qing et al., 2009 · Open in CIViC	civic
FGFR3 Y373C	Midostaurin	Predictive	D	Supports Sensitivity Response	2	submitted	EID10408 t(4;14) positive multiple myeloma cell line OPM-1 and KMS11 expressing FGFR3 Y373C were inhibited by PKC412, with relative viability dropping to 0.9/1.0 at 100 nM, 0.8/1.0 to 200 nM, 0.58/1.0 at 400 … (full text at CIViC) PMID 16091734 · Chen et al., 2005 · Open in CIViC	civic
FGFR3 Y373C	R3Mab	Predictive	D	Supports Sensitivity Response	4	submitted	EID10366 In culture, monoclonal antibody R3Mab treatment inhibited the growth of multiple myeloma cell line UTMC-2 which has wild type FGFR3 but did not affect proliferation of multiple myeloma cell line KMS11… (full text at CIViC) PMID 19381019 · Qing et al., 2009 · Open in CIViC	civic

Multiple Myeloma3

FGFR3 Y373C

(oncogenic)

Oncogenic

Supports Oncogenicity

submitted

EID10385

Ba/F3 cells transfected with wild type FGFR3 or common bladder carcinoma variant FGFR3 Y375C both resulted in IL-3 independence with FGF1 dependence for growth. However, tumors grew when multiple myel… (full text at CIViC)

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

civic

FGFR3 Y373C

Midostaurin

Predictive

Supports Sensitivity Response

submitted

EID10408

t(4;14) positive multiple myeloma cell line OPM-1 and KMS11 expressing FGFR3 Y373C were inhibited by PKC412, with relative viability dropping to 0.9/1.0 at 100 nM, 0.8/1.0 to 200 nM, 0.58/1.0 at 400 … (full text at CIViC)

PMID 16091734 · Chen et al., 2005 · Open in CIViC

civic

FGFR3 Y373C

R3Mab

Predictive

Supports Sensitivity Response

submitted

EID10366

In culture, monoclonal antibody R3Mab treatment inhibited the growth of multiple myeloma cell line UTMC-2 which has wild type FGFR3 but did not affect proliferation of multiple myeloma cell line KMS11… (full text at CIViC)

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

civic

Transitional Cell Carcinoma4
FGFR3 Y373C	Erdafitinib	Predictive	A	Supports Sensitivity Response	4	submitted	EID7308 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 Y373C	Erlotinib	Predictive	B	Supports Sensitivity Response	5	rejected	EID8879 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 alterati… (full text at CIViC) PMID 31340094 · Loriot et al., 2019 · Open in CIViC	civic
FGFR3 Y373C	Infigratinib	Predictive	C	Supports Sensitivity Response	3	submitted	EID6411 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
FGFR3 Y373C	Infigratinib	Predictive	C	Supports Sensitivity Response	3	submitted	EID6412 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 Y373C

Erdafitinib

Predictive

Supports Sensitivity Response

submitted

EID7308

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 Y373C

Erlotinib

Predictive

Supports Sensitivity Response

rejected

EID8879

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 alterati… (full text at CIViC)

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

civic

FGFR3 Y373C

Infigratinib

Predictive

Supports Sensitivity Response

submitted

EID6411

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

FGFR3 Y373C

Infigratinib

Predictive

Supports Sensitivity Response

submitted

EID6412

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

civic

Urothelial Carcinoma6
FGFR3 Y373C	Erdafitinib	Predictive	B	Supports Sensitivity Response	3	submitted	EID13203 In a bridging analysis of the phase 2 BLC2001 study of patients with metastatic or locally advanced, surgically unresectable urothelial carcinoma harboring FGFR alterations, 11 patients with FGFR3 Y37… (full text at CIViC) PMID 32304281 · Wang et al., 2020 · Open in CIViC	civic
FGFR3 Y373C	Erdafitinib	Predictive	B	Supports Sensitivity Response	3	submitted	EID13204 In a randomized controlled phase 3 trial, patients with FGFR2 or FGFR3 alterations including Y373C treated with erdafitinib vs standard chemotherapy were found to have increased overall survival (12.… (full text at CIViC) PMID 37870920 · Loriot et al., 2023 · Open in CIViC	civic
FGFR3 Y373C	Erdafitinib	Predictive	B	Supports Sensitivity Response	3	submitted	EID13205 In a phase 2 trial of patients with advanced or metastatic urothelial cancer who were positive for FGFR2 fusions or known FGFR3 variants (including Y373C), 40% of patients showed an objective response… (full text at CIViC) PMID 31340094 · Loriot et al., 2019 · Open in CIViC	civic
FGFR3 Y373C	Erdafitinib	Predictive	B	Supports Sensitivity Response	3	submitted	EID13206 In a Phase III randomized controlled trial, 351 patients with metastatic or advanced urothelial cancer with qualifying FGFR2 or FGFR3 alterations (including FGFR3 Y373C) were treated with pembrolizuma… (full text at CIViC) PMID 37871702 · Siefker-Radtke et al., 2024 · Open in CIViC	civic
FGFR3 Y373C	Erdafitinib	Predictive	C	Supports Sensitivity Response	4	submitted	EID13212 In a study of 32 patients with metastatic urothelial carcinoma who were treated with erdafitinib, tumor genomic sequencing was done using FDA-authorized MSK-IMPACT. 3 patient had FGFR3 Y373C. All thre… (full text at CIViC) PMID 37682528 · Guercio et al., 2023 · Open in CIViC	civic
FGFR3 Y373C AND FGFR3 N540K	Erdafitinib + FutibatinibSequential	Predictive	C	Supports Resistance	4	accepted	EID12704 In this study of patients with FGFR-driven urothelial carcinoma treated with selective FGFR inhibitors, longitudinal ctDNA analysis identified emergent FGFR3 kinase domain mutations at disease progres… (full text at CIViC) PMID 37377403 · Facchinetti et al., 2023 · Open in CIViC	civic

Urothelial Carcinoma6

FGFR3 Y373C

Erdafitinib

Predictive

Supports Sensitivity Response

submitted

EID13203

In a bridging analysis of the phase 2 BLC2001 study of patients with metastatic or locally advanced, surgically unresectable urothelial carcinoma harboring FGFR alterations, 11 patients with FGFR3 Y37… (full text at CIViC)

PMID 32304281 · Wang et al., 2020 · Open in CIViC

civic

FGFR3 Y373C

Erdafitinib

Predictive

Supports Sensitivity Response

submitted

EID13204

In a randomized controlled phase 3 trial, patients with FGFR2 or FGFR3 alterations including Y373C treated with erdafitinib vs standard chemotherapy were found to have increased overall survival (12.… (full text at CIViC)

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

civic

FGFR3 Y373C

Erdafitinib

Predictive

Supports Sensitivity Response

submitted

EID13205

In a phase 2 trial of patients with advanced or metastatic urothelial cancer who were positive for FGFR2 fusions or known FGFR3 variants (including Y373C), 40% of patients showed an objective response… (full text at CIViC)

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

civic

FGFR3 Y373C

Erdafitinib

Predictive

Supports Sensitivity Response

submitted

EID13206

In a Phase III randomized controlled trial, 351 patients with metastatic or advanced urothelial cancer with qualifying FGFR2 or FGFR3 alterations (including FGFR3 Y373C) were treated with pembrolizuma… (full text at CIViC)

PMID 37871702 · Siefker-Radtke et al., 2024 · Open in CIViC

civic

FGFR3 Y373C

Erdafitinib

Predictive

Supports Sensitivity Response

submitted

EID13212

In a study of 32 patients with metastatic urothelial carcinoma who were treated with erdafitinib, tumor genomic sequencing was done using FDA-authorized MSK-IMPACT. 3 patient had FGFR3 Y373C. All thre… (full text at CIViC)

PMID 37682528 · Guercio et al., 2023 · Open in CIViC

civic

FGFR3 Y373C AND FGFR3 N540K

Erdafitinib + FutibatinibSequential

Predictive

Supports Resistance

accepted

EID12704

In this study of patients with FGFR-driven urothelial carcinoma treated with selective FGFR inhibitors, longitudinal ctDNA analysis identified emergent FGFR3 kinase domain mutations at disease progres… (full text at CIViC)

PMID 37377403 · Facchinetti et al., 2023 · Open in CIViC

civic

Unmapped disease3unmapped disease
FGFR3 Y373C	(functional)	Functional	D	Supports Gain Of Function	3	submitted	EID8882 The Y373C variant was introduced into full-length FGFR3 constructs and co-transfected into NIH3T3 cells with a reporter under the control of the Fos promoter. FGFR3 Y373C resulted in a ligand-independ… (full text at CIViC) PMID 9438390 · d'Avis et al., 1998 · Open in CIViC	civic
FGFR3 Y373C	(functional)	Functional	D	Does Not Support Gain Of Function	2	submitted	EID10510 Common bladder cancer and thanatophoric dysplasia type I variant FGFR3 Y373C 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
FGFR3 Y373C	(functional)	Functional	D	Supports Gain Of Function	3	accepted	EID13201 FGFR3 Y373C expressed in 293T cells shows ligand-independent dimerization and increased autophosphorylation compared to wild type FGFR3. PMID 12009017 · Adar et al., 2002 · Open in CIViC	civic

Unmapped disease3unmapped disease

FGFR3 Y373C

(functional)

Functional

Supports Gain Of Function

submitted

EID8882

The Y373C variant was introduced into full-length FGFR3 constructs and co-transfected into NIH3T3 cells with a reporter under the control of the Fos promoter. FGFR3 Y373C resulted in a ligand-independ… (full text at CIViC)

PMID 9438390 · d'Avis et al., 1998 · Open in CIViC

civic

FGFR3 Y373C

(functional)

Functional

Does Not Support Gain Of Function

submitted

EID10510

Common bladder cancer and thanatophoric dysplasia type I variant FGFR3 Y373C 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

FGFR3 Y373C

(functional)

Functional

Supports Gain Of Function

accepted

EID13201

FGFR3 Y373C expressed in 293T cells shows ligand-independent dimerization and increased autophosphorylation compared to wild type FGFR3.

PMID 12009017 · Adar et al., 2002 · Open in CIViC

civic

Evidence by cancer (24 items)

Clinical significance (1)