ClinVar

Description

This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 832 of the ABCB11 protein (p.Arg832His). This variant is present in population databases (rs376255350, gnomAD 0.0009%). This missense change has been observed in individual(s) with progressive familial intrahepatic cholestasis (PMID: 28425419). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 499070). 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 ABCB11 protein function with a positive predictive value of 95%. This variant disrupts the p.Arg832 amino acid residue in ABCB11. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16641580, 18395098, 27114171, 28733223). 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.