Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000219509 | SCV000279974 | uncertain significance | not provided | 2023-09-05 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Invitae | RCV000526375 | SCV000649279 | uncertain significance | Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with febrile seizures plus, type 7 | 2024-01-10 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 550 of the SCN9A protein (p.Ser550Arg). This variant is present in population databases (rs200192044, gnomAD 0.004%). 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: 234892). 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 with a negative predictive value of 95%. 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. |
| ARUP Laboratories, |
RCV000219509 | SCV002049837 | uncertain significance | not provided | 2021-04-17 | criteria provided, single submitter | clinical testing | The SCN9A c.1650C>G; p.Ser550Arg variant (rs200192044), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 234892). This variant is found in the non-Finnish European population with an allele frequency of 0.0039% (5/127,678 alleles) in the Genome Aggregation Database. The serine at codon 550 is highly conserved, and computational analyses predict that this variant is deleterious (REVEL: 0.751). However, given the lack of clinical and functional data, the significance of the p.Ser550Arg variant is uncertain at this time. |
| Ambry Genetics | RCV002399799 | SCV002704164 | uncertain significance | Inborn genetic diseases | 2020-08-11 | criteria provided, single submitter | clinical testing | The p.S550R variant (also known as c.1650C>G), located in coding exon 11 of the SCN9A gene, results from a C to G substitution at nucleotide position 1650. The serine at codon 550 is replaced by arginine, 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. |
| Baylor Genetics | RCV003333054 | SCV004041437 | uncertain significance | Paroxysmal extreme pain disorder | 2023-08-29 | criteria provided, single submitter | clinical testing |