ClinVar Miner

Submissions for variant NM_003098.3(SNTA1):c.773G>A (p.Arg258Lys)

gnomAD frequency: 0.00001  dbSNP: rs776064801
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000171096 SCV000223661 uncertain significance not provided 2012-09-12 criteria provided, single submitter clinical testing The Arg258Lys variant in the SNTA1 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Arg258Lys results in a conservative amino acid substitution of one positively charged amino acid with another. This position is not conserved across species as Lysine is present at codon 258 in cow and dog. In silico analysis predicts Arg258Lys is benign to the protein structure/function. Nevertheless, the NHLBI ESP Exome Variant Server reports Arg258Lys was not observed in approximately 6,500 samples from individuals of European and African American backgrounds, indicating it is not a common benign variant in these populations. With the clinical and molecular information available at this time, we cannot definitively determine if Arg258Lys is a disease-causing mutation or a rare benign variant. The pathogenic role for this variant would be further supported if it occurred de novo in an individual or if it co-segregates with a LQTS phenotype in a family.The variant is found in LQT panel(s).
Ambry Genetics RCV002399609 SCV002669353 uncertain significance Cardiovascular phenotype 2021-02-19 criteria provided, single submitter clinical testing The p.R258K variant (also known as c.773G>A), located in coding exon 4 of the SNTA1 gene, results from a G to A substitution at nucleotide position 773. The arginine at codon 258 is replaced by lysine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. 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.
Invitae RCV003647748 SCV004547268 uncertain significance Long QT syndrome 2023-01-17 criteria provided, single submitter clinical testing This variant is present in population databases (rs776064801, gnomAD 0.003%). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SNTA1 protein function. ClinVar contains an entry for this variant (Variation ID: 190913). This variant has not been reported in the literature in individuals affected with SNTA1-related conditions. This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 258 of the SNTA1 protein (p.Arg258Lys).

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