Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001886033 | SCV002143530 | uncertain significance | Brugada syndrome | 2021-02-18 | 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. 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 SCN10A protein function. This variant has not been reported in the literature in individuals with SCN10A-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with lysine at codon 1200 of the SCN10A protein (p.Glu1200Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. |
Ambry Genetics | RCV003303269 | SCV003999214 | uncertain significance | Cardiovascular phenotype | 2023-04-27 | criteria provided, single submitter | clinical testing | The p.E1200K variant (also known as c.3598G>A), located in coding exon 20 of the SCN10A gene, results from a G to A substitution at nucleotide position 3598. The glutamic acid at codon 1200 is replaced by lysine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear. |
Gene |
RCV005232696 | SCV005875024 | uncertain significance | not provided | 2024-08-26 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |