Submissions for variant NM_001037.5(SCN1B):c.632G>A (p.Cys211Tyr)

gnomAD frequency: 0.00021  dbSNP: rs150721582

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000713013	SCV000223621	benign	not provided	2020-12-18	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 19522081, 31865891, 27207958, 25253298, 30821013)
Ambry Genetics	RCV000254246	SCV000319080	likely benign	Cardiovascular phenotype	2022-08-29	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)	RCV000713013	SCV000340803	uncertain significance	not provided	2016-05-11	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001080509	SCV000647849	likely benign	Brugada syndrome 5	2024-01-21	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000713013	SCV000843579	likely benign	not provided	2017-09-20	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000713013	SCV000886077	uncertain significance	not provided	2018-02-27	criteria provided, single submitter	clinical testing	The SCN1B c.632G>A; p.Cys211Tyr variant (rs150721582) has been reported in individuals diagnosed with Brugada syndrome, pediatric idiopathic epilepsy, and congenital atrioventricular block (Orrico 2009, Ricci 2014, Syam 2016), but was also detected in healthy control individuals (Orrico 2009). This variant is listed in the genome Aggregation Database (gnomAD) with an overall population frequency of 0.04% (identified on 107 out of 277,166 chromosomes). The cysteine at position 211 is highly conserved, considering 12 species, and computational analyses of the effects of the p.Cys211Tyr variant on protein structure and function predict a deleterious effect (SIFT: damaging, PolyPhen-2: probably damaging). Based on the available information, the clinical significance of the p.Cys211Tyr variant cannot be determined with certainty.
Mayo Clinic Laboratories, Mayo Clinic	RCV000713013	SCV001712983	uncertain significance	not provided	2019-07-14	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000713013	SCV001746566	likely benign	not provided	2024-06-01	criteria provided, single submitter	clinical testing	SCN1B: PP3, BP5, BS2
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV003989476	SCV004807338	uncertain significance	Developmental and epileptic encephalopathy, 52	2024-03-26	criteria provided, single submitter	clinical testing