ClinVar

Description

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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 COQ8A protein function. This variant has not been reported in the literature in individuals affected with COQ8A-related conditions. This variant is present in population databases (rs760655614, gnomAD 0.006%). This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 493 of the COQ8A protein (p.Asn493Ser).