ClinVar

Description

The D338G variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. However, a different missense variant at the same position (D338N) has been reported in an individual with lower and upper extremity weakness, muscle atrophy, talipes, and arthrogryposis (Scoto et al., 2015). Additionally, another missense variant at the same position (D338V) has been reported as a de novo variant in an individual with lower extremity weakness previously tested at GeneDx. The D338G variant is not observed in large population cohorts (Lek et al., 2016). This 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 conserved position within the dimerization domain of the DYNC1H1 protein. In silico analysis predicts this variant is probably damaging to the protein structure/function.