Submissions for variant NM_000142.5(FGFR3):c.188C>G (p.Pro63Arg)

dbSNP: rs371729802

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV002232281	SCV000640366	uncertain significance	not provided	2021-11-16	criteria provided, single submitter	clinical testing	In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 465348). This variant has not been reported in the literature in individuals affected with FGFR3-related conditions. This variant is present in population databases (rs371729802, gnomAD 0.007%). This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 63 of the FGFR3 protein (p.Pro63Arg).
Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital	RCV000736059	SCV000864273	likely benign	not specified	2017-07-17	criteria provided, single submitter	clinical testing	BS2, BP4; This alteration was seen in a healthy adult where full penetrance of the disorder is expected at an early age, and is predicted to be tolerated by multiple functional prediction tools.