ClinVar

Description

This sequence change replaces glycine with valine at codon 624 of the COL4A5 protein (p.Gly624Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Gly624 amino acid residue in COL4A5. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 24470729, 26934356, 21332469, 26809805, 17396119, 29854973). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 expected to disrupt COL4A5 protein function. This variant has not been reported in the literature in individuals with COL4A5-related conditions. ClinVar contains an entry for this variant (Variation ID: 1077043). This variant is not present in population databases (ExAC no frequency).