Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Biesecker Lab/Clinical Genomics Section, |
RCV000171709 | SCV000050725 | uncertain significance | not provided | 2013-06-24 | criteria provided, single submitter | research | |
Gene |
RCV000171709 | SCV000620464 | uncertain significance | not provided | 2017-08-31 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the SNTA1 gene. The G182R variant has been observed in at least one individual from a cohort of individuals not selected for cardiomyopathy, arrhythmia, or family history of sudden cardiac death, who underwent exome sequencing (Ng et al., 2013); however, a follow-up cardiac evaluation was not reported. The G182R variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The G182R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals, though arginine (R) is the wild-type amino acid in at least two species. Consequently, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. |
Invitae | RCV001359789 | SCV001555674 | uncertain significance | Long QT syndrome | 2020-07-31 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with arginine at codon 182 of the SNTA1 protein (p.Gly182Arg). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs201405395, ExAC 0.002%). This variant has not been reported in the literature in individuals with SNTA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 191510). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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. |