Submissions for variant NM_004360.5(CDH1):c.764A>G (p.Gln255Arg)

dbSNP: rs2152131091

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002024824	SCV002308337	uncertain significance	Hereditary diffuse gastric adenocarcinoma	2021-07-17	criteria provided, single submitter	clinical testing	This sequence change replaces glutamine with arginine at codon 255 of the CDH1 protein (p.Gln255Arg). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and arginine. This variant is not present in population databases (ExAC no frequency). 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This variant has not been reported in the literature in individuals affected with CDH1-related conditions.
European Reference Network on Genetic Tumour Risk Syndromes (ERN-GENTURIS), i3s - Instituto de Investigação e Inovação em Saúde, University of Porto	RCV002024824	SCV003926687	uncertain significance	Hereditary diffuse gastric adenocarcinoma	2022-08-01	criteria provided, single submitter	clinical testing	PM2 (PMID: 30311375)