Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001362469 | SCV001558486 | uncertain significance | Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with febrile seizures plus, type 7 | 2023-07-07 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 1346 of the SCN9A protein (p.Ser1346Leu). This variant is present in population databases (rs372650944, gnomAD 0.008%). 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: 1054031). 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. |
| Ambry Genetics | RCV002377516 | SCV002625240 | uncertain significance | Inborn genetic diseases | 2021-08-04 | criteria provided, single submitter | clinical testing | The p.S1346L variant (also known as c.4037C>T), located in coding exon 21 of the SCN9A gene, results from a C to T substitution at nucleotide position 4037. The serine at codon 1346 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is not well 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. |