Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000657872 | SCV000779633 | uncertain significance | not provided | 2021-01-15 | criteria provided, single submitter | clinical testing | Reported in one family with LQTS, several family members also harbor a variant in the SCN5A gene and the members of this family that harbor both variants have a more severe clinical phenotype compared to the family members that only harbor one variant (Hu et al., 2013); Published in vitro functional studies showed a more severely altered channel function in the presence of both variants compared to either the SNTA1 variant or the SCN5A variant alone (Hu et al., 2013); nevertheless, it is unclear how these studies may translate to a pathogenic role in vivo; In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 23376825) |
| Ambry Genetics | RCV002406496 | SCV002670825 | uncertain significance | Cardiovascular phenotype | 2020-10-13 | criteria provided, single submitter | clinical testing | The p.A261V variant (also known as c.782C>T), located in coding exon 4 of the SNTA1 gene, results from a C to T substitution at nucleotide position 782. The alanine at codon 261 is replaced by valine, an amino acid with similar properties. This variant has been reported in a long QT syndrome proband and her similarly affected son, both of whom also had an SCN5A variant detected; her father and daughter with only p.A261V were generally asymptomatic (Hu RM et al. Am J Physiol Heart Circ Physiol, 2013 Apr;304:H994-H1001). In vitro studies by these authors indicated that p.A261V may impact protein function; however, the combined functional impact of the SNTA1 and the SCN5A variants was more significant than either variant alone. 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, |
RCV002485491 | SCV002783932 | uncertain significance | Long QT syndrome 12 | 2021-09-21 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV002536318 | SCV003496341 | uncertain significance | Long QT syndrome | 2024-01-10 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 261 of the SNTA1 protein (p.Ala261Val). This variant is present in population databases (rs139467962, gnomAD 0.02%). This missense change has been observed in individual(s) with prolonged QT interval (PMID: 23376825). ClinVar contains an entry for this variant (Variation ID: 546085). 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%. Experimental studies have shown that this missense change affects SNTA1 function (PMID: 23376825). 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. |