Submissions for variant NM_003098.3(SNTA1):c.820C>T (p.Arg274Trp)

gnomAD frequency: 0.00004  dbSNP: rs201763667

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000469122	SCV000553688	uncertain significance	Long QT syndrome	2022-08-19	criteria provided, single submitter	clinical testing	In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The tryptophan amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 412219). This variant has not been reported in the literature in individuals affected with SNTA1-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 274 of the SNTA1 protein (p.Arg274Trp).
GeneDx	RCV000786411	SCV001987474	uncertain significance	not provided	2019-06-17	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics	RCV002429552	SCV002679726	likely benign	Cardiovascular phenotype	2021-05-26	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.
Stanford Center for Inherited Cardiovascular Disease, Stanford University	RCV000786411	SCV000925229	uncertain significance	not provided	2016-11-02	no assertion criteria provided	provider interpretation	p.Arg274Trp (c.820C>T) in SCNTA1 Seen in a family with familial DCM in our center, with a likely pathogenic DSP variant. Testing done at Invitae. This gene is a gene of uncertain significance for long QT syndrome. As such, we would by default consider it a variant of uncertain significance. We did not review it.