Submissions for variant NM_001037.5(SCN1B):c.267C>T (p.Arg89=)

gnomAD frequency: 0.00232  dbSNP: rs140949982

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000127899	SCV000171485	benign	not specified	2012-12-31	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.
Eurofins Ntd Llc (ga)	RCV000127899	SCV000228930	benign	not specified	2014-09-01	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000127899	SCV000615048	benign	not specified	2017-02-02	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001082771	SCV000647854	benign	Brugada syndrome 5	2025-02-02	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000586689	SCV000700046	benign	not provided	2016-05-16	criteria provided, single submitter	clinical testing	Variant summary: The SCN1B c.267C>T (p.Arg89=) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. 4/5 programs in Alamut predict that this variant does not affect normal splicing, however no functional studies supporting this notion were published at the time of evaluation. This variant was found in 85/121400 control chromosomes at a frequency of 0.0007002, which is approximately 70 times of the estimated maximal allele frequency of a pathogenic SCN1B variant (0.00001), suggesting this variant is a benign polymorphism. The variant was found to co-occure with a pathogenic variant, c.573_577delGCGCT in KCNH2, further suggesting non-pathogenic nature of the variant of interest. In addition, several clinical diagnostic laboratories/reputable databases classified this variant as benign. Taken together, this variant is classified as Benign.
Ambry Genetics	RCV000620631	SCV000737594	likely benign	Cardiovascular phenotype	2016-06-14	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.
CeGaT Center for Human Genetics Tuebingen	RCV000586689	SCV002498456	likely benign	not provided	2024-06-01	criteria provided, single submitter	clinical testing	SCN1B: BP4, BP7, BS2
Fulgent Genetics, Fulgent Genetics	RCV002483257	SCV002802748	likely benign	Generalized epilepsy with febrile seizures plus, type 1; Brugada syndrome 5; Atrial fibrillation, familial, 13; Developmental and epileptic encephalopathy, 52	2022-01-12	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000586689	SCV003800004	likely benign	not provided	2022-06-30	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV000127899	SCV001921576	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000586689	SCV001928504	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004544288	SCV004772802	benign	SCN1B-related disorder	2019-07-16	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).