Submissions for variant NM_000142.5(FGFR3):c.985G>A (p.Val329Ile)

gnomAD frequency: 0.00004  dbSNP: rs188723332

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001586827	SCV001820739	likely benign	not provided	2020-10-01	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 27884173, 17360555)
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001586827	SCV002049656	uncertain significance	not provided	2021-05-12	criteria provided, single submitter	clinical testing	The FGFR3 c.985G>A, p.Val329Ile variant (rs188723332) has been previously identified in a cohort of Filipino non syndromic cleft lip and palate patients (Riley 2007). While the frequency of this variant was enriched in the patient population, it was identified in several unaffected Filipino control individuals, including unaffected parents who transmitted the variant to affected probands. This variant is found in the general population with an overall allele frequency of 0.01% (31/282,186 alleles) in the Genome Aggregation Database. The valine at codon 329 is highly conserved, but computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.549). Based on the available information, the clinical significance of this variant is uncertain. References: Riley et al., Impaired FGF signaling contributes to cleft lip and palate. Proc Natl Acad Sci U S A. 2007 Mar 13;104(11):4512-7. PMID 17360555
Labcorp Genetics (formerly Invitae), Labcorp	RCV001586827	SCV002507624	likely benign	not provided	2025-01-27	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004536217	SCV004116130	uncertain significance	FGFR3-related disorder	2023-02-09	criteria provided, single submitter	clinical testing	The FGFR3 c.985G>A variant is predicted to result in the amino acid substitution p.Val329Ile. This variant was reported in an individual with cleft lip/palate (Riley et al 2007. PubMed ID: 17360555). This variant is reported in 0.12% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/4-1805473-G-A). This variant is classified as likely benign/uncertain in ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/1215889/). This variant could be benign. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001586827	SCV002036137	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001586827	SCV002038340	uncertain significance	not provided		no assertion criteria provided	clinical testing