Submissions for variant NM_001037.5(SCN1B):c.-9C>A

gnomAD frequency: 0.00603  dbSNP: rs66671189

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000127910	SCV000171496	benign	not specified	2013-03-27	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)	RCV000127910	SCV000224289	benign	not specified	2014-07-08	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000406321	SCV000411504	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	RCV000353678	SCV000411506	likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Genetic Services Laboratory, University of Chicago	RCV000127910	SCV000596952	likely benign	not specified	2015-08-06	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000587500	SCV000700049	benign	not provided	2016-04-06	criteria provided, single submitter	clinical testing	Variant summary: This c.-9C>A variant affects a non-conserved nucleotide, located in the 5' UTR, a location that could affect transcription, however, no functional studies have been performed to assess this. The variant of interest was observed in a control population (1000 Gs) with an allele frequency of 38/5008, predominantly in African cohort with an allele frequency of 0.026 (34/1322 chromosomes). This frequency exceeds the predicted maximum expected allele frequency for a pathogenic SCN1B allele (0.00001), suggesting this variant is benign. In addition, Multiple clinical laboratories have classified this variant as benign. Taken together, this variant has been classified as Benign.
Breakthrough Genomics, Breakthrough Genomics	RCV000587500	SCV005206962	likely benign	not provided		criteria provided, single submitter	not provided