Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000171121 | SCV000223686 | uncertain significance | not provided | 2011-11-28 | criteria provided, single submitter | clinical testing | The Ile135Leu variant in the SNTA1 gene has not been reported previously as a disease-causing mutation or as a benign polymorphism to our knowledge. Ile135Leu results in a conservative amino acid substitution of one non-polar residue for another at a residue that is conserved across species throughout evolution. In silico analysis predicts this change to be probably damaging to protein structure/function (6, 7). Ile135Leu was not observed in up to 600 control alleles of African American and Caucasian ethnic backgrounds tested at GeneDx, indicating it is not a common benign polymorphism in these populations. Nevertheless, no mutations have been reported in surrounding residues, indicating this region of the protein may be tolerant of change. Therefore, with the molecular and clinical information available at this time, we cannot determine whether the Ile135Leu varaint is a disease-causing mutation or a rare benign variant. A pathogenic role for Ile135Leu would be supported if it occurs de novo in an individual or co-segregates with a LQTS phenotype in a family. The variant is found in LQT panel(s). |
| Invitae | RCV001340450 | SCV001534259 | uncertain significance | Long QT syndrome | 2024-01-31 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 135 of the SNTA1 protein (p.Ile135Leu). This variant is present in population databases (rs756587722, gnomAD 0.003%). 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: 190938). 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 expected to disrupt SNTA1 protein function with a positive 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. |
| Fulgent Genetics, |
RCV002485084 | SCV002782872 | uncertain significance | Long QT syndrome 12 | 2021-10-20 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV003165351 | SCV003873704 | uncertain significance | Cardiovascular phenotype | 2022-11-15 | criteria provided, single submitter | clinical testing | The p.I135L variant (also known as c.403A>C), located in coding exon 2 of the SNTA1 gene, results from an A to C substitution at nucleotide position 403. The isoleucine at codon 135 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |