ClinVar

Description

This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 329 of the CYP1B1 protein (p.Gly329Ser). This variant is present in population databases (rs777678299, gnomAD 0.01%). This missense change has been observed in individuals with primary congenital glaucoma (PMID: 22942166). ClinVar contains an entry for this variant (Variation ID: 632362). 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 not expected to disrupt CYP1B1 protein function. Experimental studies have shown that this missense change affects CYP1B1 function (PMID: 17363580, 27243976). This variant disrupts the p.Gly329 amino acid residue in CYP1B1. Other variant(s) that disrupt this residue have been observed in individuals with CYP1B1-related conditions (PMID: 31024815), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.