Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000636283 | SCV000757722 | uncertain significance | Early infantile epileptic encephalopathy with suppression bursts | 2023-08-15 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1904 of the SCN8A protein (p.Arg1904Cys). This variant is present in population databases (rs367984544, gnomAD 0.003%). This missense change has been observed in individual(s) with SCN8A-related conditions (PMID: 33004838; Invitae). This variant is also known as c.5743C>T (p.Arg1915Cys). ClinVar contains an entry for this variant (Variation ID: 530423). 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. 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 | RCV002533204 | SCV003739712 | uncertain significance | Inborn genetic diseases | 2022-12-29 | criteria provided, single submitter | clinical testing | The c.5710C>T (p.R1904C) alteration is located in exon 27 (coding exon 26) of the SCN8A gene. This alteration results from a C to T substitution at nucleotide position 5710, causing the arginine (R) at amino acid position 1904 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |