Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000171099 | SCV000223664 | uncertain significance | not provided | 2014-04-28 | criteria provided, single submitter | clinical testing | The R331C variant has not been published as a mutation or as a benign polymorphism to our knowledge. The R331C variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Additionally, the R331C 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. Furthermore, in silico analysis predicts this variant is probably damaging to the protein structure/function. However, while other missense mutations in the same PH2 domain have been reported in association with LQTS, no missense mutations in nearby residues have been reported. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant.The variant is found in LQT panel(s). |
Invitae | RCV001852058 | SCV002141975 | uncertain significance | Long QT syndrome | 2021-06-12 | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with SNTA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 190916). This variant is present in population databases (rs769528459, ExAC 0.004%). This sequence change replaces arginine with cysteine at codon 331 of the SNTA1 protein (p.Arg331Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. |
Ambry Genetics | RCV003165350 | SCV003878378 | uncertain significance | Cardiovascular phenotype | 2023-02-08 | criteria provided, single submitter | clinical testing | The p.R331C variant (also known as c.991C>T), located in coding exon 5 of the SNTA1 gene, results from a C to T substitution at nucleotide position 991. The arginine at codon 331 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |