Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001325215 | SCV001516200 | pathogenic | Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with febrile seizures plus, type 7 | 2023-06-26 | criteria provided, single submitter | clinical testing | Experimental studies have shown that this missense change affects SCN9A function (PMID: 28381558). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Gly856 amino acid residue in SCN9A. Other variant(s) that disrupt this residue have been observed in individuals with SCN9A-related conditions (PMID: 22286749), which suggests that this may be a clinically significant amino acid residue. 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. ClinVar contains an entry for this variant (Variation ID: 1024965). This missense change has been observed in individual(s) with clinical features of familial episodic pain syndrome (PMID: 28381558; Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 856 of the SCN9A protein (p.Gly856Arg). |