Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000799328 | SCV000938987 | uncertain significance | Early infantile epileptic encephalopathy with suppression bursts | 2023-04-03 | criteria provided, single submitter | clinical testing | 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: 645276). This variant has not been reported in the literature in individuals affected with SCN8A-related conditions. This variant is present in population databases (rs142069713, gnomAD 0.003%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1904 of the SCN8A protein (p.Arg1904His). 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. |
| Ambry Genetics | RCV002345777 | SCV002649621 | uncertain significance | Inborn genetic diseases | 2017-06-14 | criteria provided, single submitter | clinical testing | The p.R1904H variant (also known as c.5711G>A), located in coding exon 26 of the SCN8A gene, results from a G to A substitution at nucleotide position 5711. The arginine at codon 1904 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is not well 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. |