Submissions for variant NM_001330260.2(SCN8A):c.4398C>G (p.Asn1466Lys)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003753672	SCV004535564	pathogenic	Early infantile epileptic encephalopathy with suppression bursts	2023-09-12	criteria provided, single submitter	clinical testing	This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Asn1466 amino acid residue in SCN8A. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 expected to disrupt SCN8A protein function. This missense change has been observed in individual(s) with infantile epileptic encephalopathy (PMID: 31054490). In at least one individual the variant was observed to be de novo. This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 1466 of the SCN8A protein (p.Asn1466Lys).