Submissions for variant NM_001330260.2(SCN8A):c.2266G>A (p.Asp756Asn)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003057861	SCV003350392	pathogenic	Early infantile epileptic encephalopathy with suppression bursts	2022-10-01	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. 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 SCN8A-related conditions (Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 756 of the SCN8A protein (p.Asp756Asn).
Institute of Human Genetics, University of Leipzig Medical Center	RCV003322638	SCV004027834	likely pathogenic	Developmental and epileptic encephalopathy, 13	2023-06-06	criteria provided, single submitter	clinical testing	Criteria applied: PS2_MOD,PS3_MOD,PS4_SUP,PM2_SUP,PP2