ClinVar

Description

Experimental studies have shown that this variant affects CYP11B1 protein function (PMID: 20089618). This variant has been observed in individual(s) with adrenal hyperplasia (PMID: 20089618). ClinVar contains an entry for this variant (Variation ID: 553208). This variant is present in population databases (rs772733691, ExAC 0.001%). This sequence change replaces tryptophan with glycine at codon 116 of the CYP11B1 protein (p.Trp116Gly). The tryptophan residue is highly conserved and there is a large physicochemical difference between tryptophan and glycine. 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 CYP11B1 protein function. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Trp116 amino acid residue in CYP11B1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15755848, 18204274, 28228528). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing.