ClinVar

Description

This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 2008 of the COL7A1 protein (p.Arg2008Gly). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal recessive dystrophic epidermolysis bullosa (PMID: 9326325, 10084325, 10504458). ClinVar contains an entry for this variant (Variation ID: 951382). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt COL7A1 protein function with a negative predictive value of 95%. Experimental studies have shown that this missense change affects COL7A1 function (PMID: 11698408, 18450758). This variant disrupts the p.Arg2008 amino acid residue in COL7A1. Other variant(s) that disrupt this residue have been observed in individuals with COL7A1-related conditions (PMID: 9740253, 10084325, 17501948), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.