Submissions for variant NM_001330260.2(SCN8A):c.5943GAG[1] (p.Ter1981=)

dbSNP: rs555793953

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000176751	SCV000228460	likely benign	not specified	2014-11-25	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000359420	SCV000379752	likely benign	Early Infantile Epileptic Encephalopathy, Autosomal Dominant	2016-06-14	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001084759	SCV000557001	benign	Early infantile epileptic encephalopathy with suppression bursts	2025-02-02	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000713152	SCV000843731	benign	not provided	2017-09-30	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002317026	SCV000850056	likely benign	Inborn genetic diseases	2016-10-10	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.
GeneDx	RCV000713152	SCV001944483	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000176751	SCV006071229	benign	not specified	2025-03-17	criteria provided, single submitter	clinical testing	Variant summary: SCN8A c.*3_*5delGAG is located in the untranslated mRNA region downstream of the termination codon. The variant allele was found at a frequency of 0.00049 in 229728 control chromosomes, predominantly at a frequency of 0.0071 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database exceeds the estimated maximal expected allele frequency for a pathogenic variant in SCN8A causing Early Infantile Epileptic Encephalopathy 13 phenotype. To our knowledge, no occurrence of c.*3_*5delGAG in individuals affected with Early Infantile Epileptic Encephalopathy 13 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 196030). Based on the evidence outlined above, the variant was classified as benign.