ClinVar

Description

This sequence change replaces serine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 156 of the CNGB3 protein (p.Ser156Ala). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CNGB3-related conditions. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on CNGB3 protein function. This variant disrupts the p.Ser156 amino acid residue in CNGB3. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15657609, 25616768, 28795510). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.