Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000802884 | SCV000942731 | uncertain significance | Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with febrile seizures plus, type 7 | 2023-06-24 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 1883 of the SCN9A protein (p.Thr1883Ser). This variant is present in population databases (no rsID available, gnomAD 0.0009%). 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: 648209). 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. |
New York Genome Center | RCV001592992 | SCV001815753 | uncertain significance | Generalized epilepsy with febrile seizures plus, type 7 | 2020-08-14 | criteria provided, single submitter | clinical testing | The c.5681C>G, p.Thr1894Ser missense variant identified in the SCN9A gene has not been reported in the literature. This variant has anallele frequency of 0.001 (2 heterozygous/ 143,284alleles) in the gnomAD v3 database, indicating this is a rare allele. The threonine residue at AA position 1894 is highly conserved and there is a small physicochemical difference between threonine and serine. In silico analysis predicts conflicting evidence of pathogenicity [PMID: 27268795]. Based on the available evidence, the variant c.5681C>G, p.Thr1894Ser in the SCN9A gene is classified as a Variant of Uncertain Significance. |