ClinVar

Description

A novel G942D pathogenic variant was identified in the COL2A1 gene. It has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. G942D occurs in the triple helical domain and replaces the Glycine in the canonical Gly-X-Y repeat. Mutations in these Glycines result in poor winding of the collagen triple helix and a less functional protein. The G942D variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. G942D is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants in nearby residues (R940Q, G945S) have been reported in the Human Gene Mutation Database in association with skeletal dysplasias (Stenson et al., 2014), supporting the functional importance of this region of the protein.