Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000171118 | SCV000223683 | uncertain significance | not provided | 2016-11-17 | criteria provided, single submitter | clinical testing | The Gly186Ser variant in the SNTA1 gene has not been reported previously as a disease-causing mutation nor as a benign polymorphism, to our knowledge. Gly186Ser results in a non-conservative amino acid substitution of a non-polar Glycine with a neutral, polar Serine at a residue that is conserved across mammal species. The Gly186Ser variant was not detected in up to 600 alleles from control individuals of Caucasian and African American ancestry tested at GeneDx, indicating it is not a common benign variant in these populations. However, no mutations have been reported in this region of the SNTA1 gene to date. In summary, with the clinical and molecular information available at this time, we cannot unequivocally determine whether the Gly186Ser variant is a disease-causing mutation or a rare benign variant. The pathogenic role of this variant would be supported if it arose de novo in an individual or co-segregates with an LQTS phenotype in a family. The variant is found in LQT panel(s). |
Invitae | RCV000631640 | SCV000752723 | uncertain significance | Long QT syndrome | 2023-09-06 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 186 of the SNTA1 protein (p.Gly186Ser). This variant is present in population databases (rs200755101, gnomAD 0.005%). 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: 190935). 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. |
Ambry Genetics | RCV002345577 | SCV002650908 | uncertain significance | Cardiovascular phenotype | 2023-01-17 | criteria provided, single submitter | clinical testing | The c.556G>A (p.G186S) alteration is located in exon 3 (coding exon 3) of the SNTA1 gene. This alteration results from a G to A substitution at nucleotide position 556, causing the glycine (G) at amino acid position 186 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Fulgent Genetics, |
RCV002485083 | SCV002792727 | uncertain significance | Long QT syndrome 12 | 2022-02-15 | criteria provided, single submitter | clinical testing |