Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000701512 | SCV000830315 | uncertain significance | Early infantile epileptic encephalopathy with suppression bursts | 2022-10-17 | 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: 578492). This variant has not been reported in the literature in individuals affected with SCN8A-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 1975 of the SCN8A protein (p.Val1975Ala). |
| New York Genome Center | RCV001592898 | SCV001815709 | uncertain significance | Seizures, benign familial infantile, 5 | 2020-11-04 | criteria provided, single submitter | clinical testing | The inherited heterozygous missense variant c.5924T>C, p.Val1975Ala in the SCN8A gene has not been reported in the available literature. The variant is not present in the gnomAD database, indicating this is a rare allele. In silico tools, predict conflicting evidence of pathogenicity (PMID: 27268795). Based on the available evidence, the c.5924T>C, p.Val1975Ala variant in the SCN8A gene is classified as a variant of uncertain significance. |