Submissions for variant NM_001330260.2(SCN8A):c.3148G>A (p.Gly1050Ser)

gnomAD frequency: 0.00017  dbSNP: rs202006479

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000514951	SCV000242934	likely benign	not provided	2019-01-21	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 27875746, 25666757)
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000514951	SCV000609625	uncertain significance	not provided	2017-05-12	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000703972	SCV000832903	benign	Early infantile epileptic encephalopathy with suppression bursts	2025-01-27	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000514951	SCV001148740	uncertain significance	not provided	2023-05-01	criteria provided, single submitter	clinical testing	SCN8A: PP2
New York Genome Center	RCV001838987	SCV002099095	uncertain significance	Seizures, benign familial infantile, 5	2021-03-05	criteria provided, single submitter	clinical testing	The inherited heterozygous c.3148G>A (p.Gly1050Ser) variant identified in the SCN8A gene has been reported in the literature as de novo in a patient affected with hemiplegic cerebral palsy and intellectual disability [2]. The variant has been reported in ClinVar database with conflicting interpretations of pathogenicity [benign (1), likely benign (1), uncertain significance (2). Variation ID:207142]. The variant has 0.0001709 allele frequency in the gnomAD(v3) database (26 out of 152168 heterozygous alleles, no homozygotes) suggesting it is not a common benign variant in the populations represented in that database. The affected residue is evolutionarily conserved and is predicted deleterious by in silico predictiontools [CADD score= 22.5, REVEL score = 0.828]. Based on the available evidence, the inherited heterozygous c.3148G>A (p.Gly1050Ser) variant identified in the SCN8A gene is reported as a variant of uncertainsignificance.
Ambry Genetics	RCV002321764	SCV002610427	likely benign	Inborn genetic diseases	2017-10-12	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
PreventionGenetics, part of Exact Sciences	RCV004537587	SCV004743664	likely benign	SCN8A-related disorder	2022-01-04	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).