ClinVar Miner

Submissions for variant NM_003098.3(SNTA1):c.1388T>G (p.Leu463Arg)

gnomAD frequency: 0.00002  dbSNP: rs188835994
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000520393 SCV000618086 uncertain significance not provided 2017-07-05 criteria provided, single submitter clinical testing The L463R variant of uncertain significance in the SNTA1 gene has not been published as pathogenic or been reported as benign to our knowledge. This variant has been identified in conjunction with a KCNH2 pathogenic variant in one other proband referred for LQTS testing at GeneDx. L463R has been observed in 5/11,572 (0.04%) alleles from individuals of Latino ancestry in the Exome Aggregation Consortium (Lek et al., 2016). The L463R 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. Moreover, this substitution occurs at a position that is conserved in mammals. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.
Invitae RCV001349981 SCV001544351 uncertain significance Long QT syndrome 2023-12-20 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 463 of the SNTA1 protein (p.Leu463Arg). This variant is present in population databases (rs188835994, gnomAD 0.05%). 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: 449724). 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 with a negative predictive value of 80%. 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.
Ambry Genetics RCV002395247 SCV002702690 uncertain significance Cardiovascular phenotype 2020-03-12 criteria provided, single submitter clinical testing The p.L463R variant (also known as c.1388T>G), located in coding exon 7 of the SNTA1 gene, results from a T to G substitution at nucleotide position 1388. The leucine at codon 463 is replaced by arginine, an amino acid with dissimilar 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.
Fulgent Genetics, Fulgent Genetics RCV002481701 SCV002794523 uncertain significance Long QT syndrome 12 2021-09-14 criteria provided, single submitter clinical testing

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