Submissions for variant NM_003098.3(SNTA1):c.514G>A (p.Val172Ile)

gnomAD frequency: 0.00001  dbSNP: rs775580363

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000274218	SCV000433511	uncertain significance	Long QT syndrome 12	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina	RCV000331608	SCV000433512	uncertain significance	Congenital long QT syndrome	2016-06-14	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000620625	SCV000737760	uncertain significance	Cardiovascular phenotype	2022-07-18	criteria provided, single submitter	clinical testing	The p.V172I variant (also known as c.514G>A), located in coding exon 3 of the SNTA1 gene, results from a G to A substitution at nucleotide position 514. The valine at codon 172 is replaced by isoleucine, 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. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear.
Invitae	RCV001861164	SCV002288812	uncertain significance	Long QT syndrome	2021-09-24	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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 338218). This variant has not been reported in the literature in individuals affected with SNTA1-related conditions. This variant is present in population databases (rs775580363, ExAC 0.006%). This sequence change replaces valine with isoleucine at codon 172 of the SNTA1 protein (p.Val172Ile). The valine residue is weakly conserved and there is a small physicochemical difference between valine and isoleucine.