ClinVar

Description

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 96 of the CYP17A1 protein (p.Arg96Gln). This variant is present in population databases (rs104894153, gnomAD 0.004%). This missense change has been observed in individuals with autosomal recessive congenital adrenal hyperplasia (PMID: 16569739, 21846181, 23291414, 23466679, 26543560, 28008861). ClinVar contains an entry for this variant (Variation ID: 1802). 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 CYP17A1 protein function with a positive predictive value of 95%. This variant disrupts the p.Arg96 amino acid residue in CYP17A1. Other variant(s) that disrupt this residue have been observed in individuals with CYP17A1-related conditions (PMID: 8550762, 21340163), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.