Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001060481 | SCV001225173 | uncertain significance | Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with febrile seizures plus, type 7 | 2023-05-23 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SCN9A-related conditions. ClinVar contains an entry for this variant (Variation ID: 855256). 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. 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. This sequence change replaces threonine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 994 of the SCN9A protein (p.Thr994Asn). |
Ambry Genetics | RCV002436639 | SCV002746293 | uncertain significance | Inborn genetic diseases | 2021-07-11 | criteria provided, single submitter | clinical testing | The p.T994N variant (also known as c.2981C>A), located in coding exon 16 of the SCN9A gene, results from a C to A substitution at nucleotide position 2981. The threonine at codon 994 is replaced by asparagine, an amino acid with similar properties. This amino acid position is conserved. 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. |