Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001065098 | SCV001230037 | uncertain significance | Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with febrile seizures plus, type 7 | 2023-11-07 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1279 of the SCN9A protein (p.Arg1279Gln). This variant is present in population databases (rs368396027, gnomAD 0.01%). This missense change has been observed in individual(s) with small fibre neuropathy (PMID: 30554136). ClinVar contains an entry for this variant (Variation ID: 859073). 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 | RCV002365757 | SCV002626008 | uncertain significance | Inborn genetic diseases | 2022-01-10 | criteria provided, single submitter | clinical testing | The p.R1279Q variant (also known as c.3836G>A), located in coding exon 20 of the SCN9A gene, results from a G to A substitution at nucleotide position 3836. The arginine at codon 1279 is replaced by glutamine, an amino acid with highly similar properties. This alteration was detected in a cohort of small fiber neuropathy patients; however, clinical details were limited (Eijkenboom I et al. J Neurol Neurosurg Psychiatry, 2019 03;90:342-352). 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. |