Submissions for variant NM_001037.5(SCN1B):c.412G>A (p.Val138Ile)

gnomAD frequency: 0.00058  dbSNP: rs72558029

Total submissions: 17

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000171023	SCV000050710	benign	not provided	2020-02-21	criteria provided, single submitter	research
Blueprint Genetics	RCV000193746	SCV000207216	likely benign	not specified	2015-11-10	criteria provided, single submitter	clinical testing
GeneDx	RCV000171023	SCV000223587	benign	not provided	2018-07-13	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 28704380, 24529773)
Agnes Ginges Centre for Molecular Cardiology, Centenary Institute	RCV000172897	SCV000223888	likely benign	Long QT syndrome	2015-03-27	criteria provided, single submitter	research	The SCN1B Val138Ile variant has been previously reported. It is observed in the Exome Aggregation Consortium dataset (http://exac.broadinstitute.org/) with an allele frequency of 0.012 (1418/121366 alleles); and the frequency in the South Asian subpopulation is 0.08. In-silico software tools predict this variant to be tolerable (SIFT "tolerated"; PholyPhen2 "benign", MutationTaster "polymorphism"). We identified this variant in a female with an undetermined heart disease, normal echocardiogram, paroxysmal atrial fibrillation and non-sustained ventricular tachycardia. There is no clear family history of disease. Based on the high frequency (>1%) observed in the general population, we have classified this variant as "likely benign".
Genetic Services Laboratory, University of Chicago	RCV000193746	SCV000248800	likely benign	not specified	2015-05-15	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001084740	SCV000252899	benign	Brugada syndrome 5	2024-01-27	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000248951	SCV000318186	benign	Cardiovascular phenotype	2019-09-16	criteria provided, single submitter	clinical testing	This alteration is classified as 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	RCV001084740	SCV000411522	benign	Brugada syndrome 5	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV000401928	SCV000411524	benign	Generalized epilepsy with febrile seizures plus, type 1	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Athena Diagnostics	RCV000171023	SCV001145385	benign	not provided	2019-03-08	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000171023	SCV002048976	benign	not provided	2020-10-29	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000171023	SCV005206966	likely benign	not provided		criteria provided, single submitter	not provided
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000171023	SCV001797657	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000193746	SCV001925642	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000171023	SCV001932319	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000193746	SCV001954234	benign	not specified		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004734748	SCV005352480	benign	SCN1B-related disorder	2024-06-15	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).