ClinVar

Description

This variant is present in population databases (rs150153987, gnomAD 0.01%). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg563 amino acid residue in CNGA3. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11536077, 15743887, 17693388; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this missense change affects CNGA3 function (PMID: 18445228). 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 CNGA3 protein function. ClinVar contains an entry for this variant (Variation ID: 596480). This missense change has been observed in individuals with achromatopsia (PMID: 18445228, 30682209). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 563 of the CNGA3 protein (p.Arg563Cys).