Submissions for variant NM_001330260.2(SCN8A):c.5630A>G (p.Asn1877Ser)

dbSNP: rs587780455

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000118288	SCV000152660	uncertain significance	not provided	2013-12-06	criteria provided, single submitter	clinical testing
GeneDx	RCV000118288	SCV000242923	pathogenic	not provided	2021-03-25	criteria provided, single submitter	clinical testing	Not observed in large population cohorts (Lek et al., 2016); The majority of missense variants in this gene are considered pathogenic (Stenson et al., 2014); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This substitution is predicted to be within the C-terminal cytoplasmic domain; This variant is associated with the following publications: (PMID: 29100083, 27210545, 30851583, 31164858, 32090326, 27875746, 27864847, 28923014, 30776697, 31487502, 32853054, 32040247)
Eurofins Ntd Llc (ga)	RCV000118288	SCV000338930	uncertain significance	not provided	2016-01-12	criteria provided, single submitter	clinical testing
Neurogenetics Laboratory - MEYER, AOU Meyer	RCV000416967	SCV000494532	likely pathogenic	Focal epilepsy	2016-11-16	criteria provided, single submitter	clinical testing
Invitae	RCV000467598	SCV000544808	pathogenic	Early infantile epileptic encephalopathy with suppression bursts	2023-07-12	criteria provided, single submitter	clinical testing	This missense change has been observed in individual(s) with early onset focal epileptic seizures without cognitive or neurological impairment (PMID: 27210545; Invitae). In at least one individual the variant was observed to be de novo. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 130252). 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. For these reasons, this variant has been classified as Pathogenic. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 1877 of the SCN8A protein (p.Asn1877Ser).
Mendelics	RCV000239630	SCV001138743	likely pathogenic	Developmental and epileptic encephalopathy, 13	2019-05-28	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000118288	SCV001247160	pathogenic	not provided	2022-02-01	criteria provided, single submitter	clinical testing
Génétique des Maladies du Développement, Hospices Civils de Lyon	RCV000239702	SCV001450736	pathogenic	Seizures, benign familial infantile, 5	2020-12-16	criteria provided, single submitter	clinical testing	Absent from gnomAD. Predicted pathogenic. Genotype/phenotype correlation
Revvity Omics, Revvity	RCV000118288	SCV002020030	pathogenic	not provided	2019-02-06	criteria provided, single submitter	clinical testing
University of British Columbia, BC Children's Hospital	RCV000239702	SCV004031479	pathogenic	Seizures, benign familial infantile, 5	2023-08-30	criteria provided, single submitter	research
OMIM	RCV000239702	SCV000297996	pathogenic	Seizures, benign familial infantile, 5	2020-10-19	no assertion criteria provided	literature only
Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille	RCV000239630	SCV001428375	likely pathogenic	Developmental and epileptic encephalopathy, 13	2019-01-01	no assertion criteria provided	clinical testing
OMIM	RCV000239630	SCV001438355	pathogenic	Developmental and epileptic encephalopathy, 13	2020-10-19	no assertion criteria provided	literature only
Diagnostic Laboratory, Strasbourg University Hospital	RCV002274920	SCV002562870	pathogenic	Seizure		no assertion criteria provided	clinical testing