Description
The A1650T pathogenic variant in the SCN8A gene has been reported previously as a de novo variant in two unrelated individuals whose combined features include intractable early-onset epileptic encephalopathy, severely regressed development, intellectual disability, quadriparesis with dystonic posturing, hypotonia, and MRI abnormalities including asymmetric ventricles and mild diffuse atrophy (Larsen et al., 2015; Ohba et al., 2014). The A1650T 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 A1650T 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 and in silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret A1650T as a pathogenic variant.
| # | Sample | Method | Observation |
|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
|---|
| 1 | germline | yes | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |
