Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000802375 | SCV000942202 | uncertain significance | Early infantile epileptic encephalopathy with suppression bursts | 2023-08-07 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SCN8A protein function. ClinVar contains an entry for this variant (Variation ID: 647793). This variant has not been reported in the literature in individuals affected with SCN8A-related conditions. This variant is present in population databases (rs371383623, gnomAD 0.002%). This sequence change replaces glutamic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 507 of the SCN8A protein (p.Glu507Ala). |
| Ambry Genetics | RCV002388489 | SCV002705307 | uncertain significance | Inborn genetic diseases | 2018-12-04 | criteria provided, single submitter | clinical testing | The p.E507A variant (also known as c.1520A>C), located in coding exon 10 of the SCN8A gene, results from an A to C substitution at nucleotide position 1520. The glutamic acid at codon 507 is replaced by alanine, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |