Submissions for variant NM_001330260.2(SCN8A):c.4787C>G (p.Ser1596Cys)

dbSNP: rs879255705

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001854935	SCV002240061	pathogenic	Early infantile epileptic encephalopathy with suppression bursts	2022-11-01	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. ClinVar contains an entry for this variant (Variation ID: 253290). This missense change has been observed in individual(s) with SCN8A-related conditions (PMID: 25785782, 26252990). 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 serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 1596 of the SCN8A protein (p.Ser1596Cys).
GeneReviews	RCV000239762	SCV000298206	not provided	Developmental and epileptic encephalopathy, 13		no assertion provided	literature only
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001528565	SCV001740487	pathogenic	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001528565	SCV001932073	pathogenic	not provided		no assertion criteria provided	clinical testing