Submissions for variant NM_001037.5(SCN1B):c.28G>A (p.Gly10Ser)

gnomAD frequency: 0.00249  dbSNP: rs72552027

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000588361	SCV000223613	benign	not provided	2019-07-02	criteria provided, single submitter	clinical testing	Reported in one African American infant with sudden infant death sydnrome (SIDS) and in one healthy, ethnically-matched control individual (Tan et al., 2010); Reported in one patient with LQTS (Rurio et al., 2014); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 24662403, 20226894)
Ambry Genetics	RCV000254455	SCV000318519	likely benign	Cardiovascular phenotype	2018-12-14	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.
Eurofins Ntd Llc (ga)	RCV000171049	SCV000340537	likely benign	not specified	2016-04-13	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001080647	SCV000411507	likely benign	Brugada syndrome 5	2017-04-28	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000299875	SCV000411508	likely benign	Generalized epilepsy with febrile seizures plus, type 1	2017-04-28	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Athena Diagnostics	RCV000171049	SCV000615049	uncertain significance	not specified	2016-12-15	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001080647	SCV000647856	benign	Brugada syndrome 5	2025-01-30	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000588361	SCV000700047	likely benign	not provided	2016-06-17	criteria provided, single submitter	clinical testing	Variant summary: The SCN1B c.28G>A (p.Gly10Ser) variant involves the alteration of a non-conserved nucleotide, is not located in a known functional domain, and 2/4 in silico tools predict a benign outcome (SNPs&GO not captured due to low reliability index). This variant was found in 16/5008 control chromosomes, predominantly observed in the African subpopulation (16/1322 African alleles from 1000G; 0.01210). This frequency is significantly greater than the estimated maximal expected allele frequency of a pathogenic SCN1B variant (0.00001), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. However, the site is covered in fewer than 80% of the individuals in ExAC, which may indicate a low-quality site. The variant was identified in one SIDS case (also found in healthy African American adult control) and one LQTS patient without evidence of causality (i.e. co-segregation). In addition, one clinical diagnostic laboratory classified this variant as a VUS. Taken together and based on the allele frequency in the African subpopulation, this variant is classified as Likely Benign until additional information is available.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000588361	SCV001471695	uncertain significance	not provided	2020-01-31	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004539576	SCV004775408	likely benign	SCN1B-related disorder	2021-11-22	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).