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. This variant disrupts the p.Gly503 amino acid residue in CYP4V2. Other variant(s) that disrupt this residue have been observed in individuals with CYP4V2-related conditions (PMID: 30429639), which suggests that this may be a clinically significant amino acid residue. 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 CYP4V2 protein function. This missense change has been observed in individual(s) with Bietti crystalline dystrophy (PMID: 34923510). This variant is present in population databases (rs750524069, gnomAD 0.03%). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 503 of the CYP4V2 protein (p.Gly503Arg).