ClinVar

Description

This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 117 of the CYP1B1 protein (p.Arg117Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with congenital glaucoma (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 2098650). 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 CYP1B1 protein function. This variant disrupts the p.Arg117 amino acid residue in CYP1B1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 17893647, 27243976). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.