Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001233862 | SCV001406476 | uncertain significance | Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with febrile seizures plus, type 7 | 2021-01-31 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This sequence change replaces valine with glycine at codon 258 of the SCN9A protein (p.Val258Gly). The valine residue is highly conserved and there is a moderate physicochemical difference between valine and glycine. This variant is present in population databases (rs757286231, ExAC 0.002%). This variant has not been reported in the literature in individuals with SCN9A-related conditions. 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 | RCV002402731 | SCV002672142 | uncertain significance | Inborn genetic diseases | 2019-12-26 | criteria provided, single submitter | clinical testing | The p.V258G variant (also known as c.773T>G), located in coding exon 6 of the SCN9A gene, results from a T to G substitution at nucleotide position 773. The valine at codon 258 is replaced by glycine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |