Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001064414 | SCV001229317 | uncertain significance | Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with febrile seizures plus, type 7 | 2023-10-22 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 1178 of the SCN9A protein (p.Val1178Gly). This variant is present in population databases (rs761337631, gnomAD 0.005%). 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: 858525). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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 | RCV003259075 | SCV003972544 | uncertain significance | Inborn genetic diseases | 2023-04-28 | criteria provided, single submitter | clinical testing | The c.3533T>G (p.V1178G) alteration is located in exon 19 (coding exon 18) of the SCN9A gene. This alteration results from a T to G substitution at nucleotide position 3533, causing the valine (V) at amino acid position 1178 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |