ClinVar Miner

Submissions for variant NM_003098.3(SNTA1):c.1279A>G (p.Ile427Val)

gnomAD frequency: 0.00001  dbSNP: rs151158866
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000171105 SCV000223670 uncertain significance not provided 2012-08-13 criteria provided, single submitter clinical testing The Ile427Val variant in the SNTA1 gene has not been reported previously as a disease-causing mutation nor as a benign polymorphism, to our knowledge. Ile427Val results in a conservative substitution of one non-polar amino acid for another at a residue that is conserved across species. As a result, in silico analysis predicts Ile427Val likely has a benign effect on the protein structure/function. In addition, no pathogenic mutations have been reported in this region of the SNTA1 gene to date, indicating this region of the protein may tolerate change. However, the NHLBI ESP Exome Variant Server reports Ile427Val was observed with a very low frequency in individuals of European ancestry (1/8,599 alleles) and individuals of African American ancestry (1/4,405 alleles), indicating it is not a common benign variant in these populations. In summary, the clinical significance of the Ile427Val variant in the SNTA1 gene is currently unknown. A pathogenic role for this variant would be supported if it has occurred de novo in an individual or co-segregates with a LQTS phenotype in a family.
Ambry Genetics RCV002372066 SCV002686062 uncertain significance Cardiovascular phenotype 2022-07-15 criteria provided, single submitter clinical testing The p.I427V variant (also known as c.1279A>G), located in coding exon 7 of the SNTA1 gene, results from an A to G substitution at nucleotide position 1279. The isoleucine at codon 427 is replaced by valine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear.
Invitae RCV003647749 SCV004523110 uncertain significance Long QT syndrome 2023-09-10 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 427 of the SNTA1 protein (p.Ile427Val). This variant is present in population databases (rs151158866, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with SNTA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 190922). 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. 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.

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