Submissions for variant NM_001165963.4(SCN1A):c.1378-3T>C

gnomAD frequency: 0.00016  dbSNP: rs150964803

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000127874	SCV000171458	benign	not specified	2013-04-03	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000469921	SCV000559704	likely benign	Early infantile epileptic encephalopathy with suppression bursts	2025-01-25	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000127874	SCV000596946	likely benign	not specified	2015-12-17	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002316401	SCV000851684	likely benign	Inborn genetic diseases	2018-05-23	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.
Illumina Laboratory Services, Illumina	RCV001134809	SCV001294568	likely benign	Migraine, familial hemiplegic, 3	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina	RCV001134810	SCV001294569	uncertain significance	Generalized epilepsy with febrile seizures plus, type 2	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000127874	SCV003845000	benign	not specified	2023-02-03	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001529594	SCV004147186	likely benign	not provided	2024-05-01	criteria provided, single submitter	clinical testing	SCN1A: BP4, BS1
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001529594	SCV001743291	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001529594	SCV001927482	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004544285	SCV004790707	likely benign	SCN1A-related disorder	2024-04-30	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).