Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000647793 | SCV000769596 | uncertain significance | Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with febrile seizures plus, type 7 | 2023-12-09 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 582 of the SCN9A protein (p.Glu582Lys). This variant is present in population databases (rs201391809, gnomAD 0.03%). This missense change has been observed in individual(s) with Dravet syndrome. However, this individual was also observed to carry a de novo pathogenic variant in SCN1A (PMID: 23895530). ClinVar contains an entry for this variant (Variation ID: 538474). 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 SCN9A protein function with a negative predictive value of 95%. 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. |
Baylor Genetics | RCV001336520 | SCV001529922 | uncertain significance | Generalized epilepsy with febrile seizures plus, type 7 | 2018-03-20 | criteria provided, single submitter | clinical testing | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. |
Ambry Genetics | RCV002397277 | SCV002711357 | uncertain significance | Inborn genetic diseases | 2019-09-27 | criteria provided, single submitter | clinical testing | The p.E582K variant (also known as c.1744G>A), located in coding exon 11 of the SCN9A gene, results from a G to A substitution at nucleotide position 1744. The glutamic acid at codon 582 is replaced by lysine, an amino acid with similar properties. This amino acid position is 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. |
Revvity Omics, |
RCV003140038 | SCV003826969 | uncertain significance | not provided | 2020-10-13 | criteria provided, single submitter | clinical testing |