Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV005111816 | SCV005734049 | pathogenic | Early infantile epileptic encephalopathy with suppression bursts | 2024-12-31 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 1621 of the SCN8A protein (p.Leu1621Phe). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with SCN8A-related conditions (internal data). In at least one individual the variant was observed to be de novo. Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt SCN8A protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic. |