Submissions for variant NM_003098.3(SNTA1):c.1350C>T (p.Phe450=)

gnomAD frequency: 0.01203  dbSNP: rs116747979

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000231537	SCV000287865	benign	Long QT syndrome	2024-01-29	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001094612	SCV000433485	benign	Long QT syndrome 12	2018-01-12	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	RCV000308797	SCV000433486	likely benign	Congenital long QT syndrome	2016-06-14	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000617972	SCV000735234	benign	Cardiovascular phenotype	2015-12-02	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000781874	SCV000920253	benign	not specified	2018-09-17	criteria provided, single submitter	clinical testing	Variant summary: SNTA1 c.1350C>T alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0035 in 277164 control chromosomes, predominantly at a frequency of 0.036 within the African subpopulation in the gnomAD database, including 16 homozygotes. The observed variant frequency within African control individuals in the gnomAD database is approximately 3600-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 a benign polymorphism found primarily in populations of African origin. To our knowledge, no occurrence of c.1350C>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	RCV001094612	SCV001471033	benign	Long QT syndrome 12	2023-09-21	criteria provided, single submitter	clinical testing
GeneDx	RCV001706257	SCV001861956	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing