Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000478102 | SCV000569932 | likely pathogenic | not provided | 2016-07-21 | criteria provided, single submitter | clinical testing | A variant that is likely pathogenic has been identified in the SCN8A gene. The L257V variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,400 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This substitution occurs at a conserved position predicted to be within transmembrane segment S5 in the first homologous domain of the SCN8A protein. Additionally, in silico analysis predicts this variant is probably damaging to the protein structure/function. However, the L257V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Additionally, targeted parental test results indicate this variant is assumed de novo. Therefore, we now interpret L257V as a likely pathogenic variant; however, the possibility that it is benign cannot be excluded. |