Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000686484 | SCV000814003 | uncertain significance | Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with febrile seizures plus, type 7 | 2022-08-07 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 634 of the SCN9A protein (p.Arg634Cys). This variant is present in population databases (rs371543591, 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: 566621). 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 tolerated. 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 | RCV002547101 | SCV003652588 | uncertain significance | Inborn genetic diseases | 2022-11-01 | criteria provided, single submitter | clinical testing | The c.1900C>T (p.R634C) alteration is located in exon 12 (coding exon 11) of the SCN9A gene. This alteration results from a C to T substitution at nucleotide position 1900, causing the arginine (R) at amino acid position 634 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |