ClinVar

Description

This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 286 of the CLCN7 protein (p.Arg286Trp). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individuals with autosomal dominant osteopetrosis (PMID: 11741829, 17164308, 21962762, 30942407, 31412925). ClinVar contains an entry for this variant (Variation ID: 1068483). 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 CLCN7 protein function. Experimental studies have shown that this missense change affects CLCN7 function (PMID: 19543743). For these reasons, this variant has been classified as Pathogenic.