Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002316847 | SCV000850618 | uncertain significance | Inborn genetic diseases | 2017-04-20 | criteria provided, single submitter | clinical testing | The p.S613G variant (also known as c.1837A>G), located in coding exon 11 of the SCN8A gene, results from an A to G substitution at nucleotide position 1837. The serine at codon 613 is replaced by glycine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV003588674 | SCV004273066 | uncertain significance | Early infantile epileptic encephalopathy with suppression bursts | 2023-12-18 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 613 of the SCN8A protein (p.Ser613Gly). This variant is present in population databases (rs749121003, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with SCN8A-related conditions. ClinVar contains an entry for this variant (Variation ID: 589621). 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 with a negative predictive value of 95%. 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. |