Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000236737 | SCV000294019 | likely pathogenic | not provided | 2016-03-06 | criteria provided, single submitter | clinical testing | The D338V variant in the DYNC1H1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. This 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. The D338V 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 is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. A missense variant in this residue (D338N) has been previously reported in association with spinal muscular atrophy with lower extremity predominance (Scoto et al., 2015), supporting the functional importance of this region of the protein. The D338V variant is a strong candidate for a pathogenic variant |