Submissions for variant NM_003098.3(SNTA1):c.555C>T (p.Val185=)

gnomAD frequency: 0.00948  dbSNP: rs34995247

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000248085	SCV000317857	benign	Cardiovascular phenotype	2016-01-06	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	RCV000318116	SCV000433509	likely benign	Congenital long QT syndrome	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001094752	SCV000433510	benign	Long QT syndrome 12	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.
Invitae	RCV000375094	SCV000563492	benign	Long QT syndrome	2024-01-31	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000780739	SCV000918251	benign	not specified	2018-04-16	criteria provided, single submitter	clinical testing	Variant summary: SNTA1 c.555C>T alters a non-conserved nucleotide resulting in a synonymous change. The variant allele was found at a frequency of 0.0027 in 121272 control chromosomes in the ExAC database, including 2 homozygotes. The observed variant frequency is approximately 273.76 fold of the estimated maximal expected allele frequency for a pathogenic variant in SNTA1 causing Arrhythmia phenotype (1e-05), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.555C>T in individuals affected with Arrhythmia and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001094752	SCV001472221	benign	Long QT syndrome 12	2019-11-21	criteria provided, single submitter	clinical testing
GeneDx	RCV001706407	SCV001895469	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV000780739	SCV001919252	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000780739	SCV001956525	benign	not specified		no assertion criteria provided	clinical testing