ClinVar

Description

The G1266D variant in the COL4A1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The G1266D variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The G1266D variant 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. A missense variants in the same residue (G1266R) has been reported in association with a COL4A1-related disorder (Shah et al., 2012), supporting the functional importance of this residue. The G1266D variant is a strong candidate for a pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded.