ClinVar

Description

A variant that is likely pathogenic has been identified in the GJB1 gene. The C60R variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. However, a different amino acid substitution at the same position (C60F) has been previously reported in a family with CMTX1 (Fairweather et al., 1994). The C60R variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The C60R 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. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.