ClinVar

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Cys1195 amino acid residue in COL1A2. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 COL1A2 protein function. ClinVar contains an entry for this variant (Variation ID: 1498972). This missense change has been observed in individual(s) with autosomal dominant osteogenesis imperfecta (PMID: 30715774; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 1195 of the COL1A2 protein (p.Cys1195Arg).