Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ce |
RCV001092244 | SCV001248657 | pathogenic | not provided | 2022-11-01 | criteria provided, single submitter | clinical testing | SCN11A: PP1:Strong, PS4, PM2, PM5 |
Invitae | RCV002554846 | SCV003294708 | pathogenic | Hereditary sensory and autonomic neuropathy type 7; Familial episodic pain syndrome with predominantly lower limb involvement | 2022-10-17 | criteria provided, single submitter | clinical testing | 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 expected to disrupt SCN11A protein function. ClinVar contains an entry for this variant (Variation ID: 872004). This missense change has been observed in individuals with familial episodic pain syndrome (PMID: 27224030, 27503742, 30557356). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 222 of the SCN11A protein (p.Arg222His). Experimental studies have shown that this missense change affects SCN11A function (PMID: 27503742). For these reasons, this variant has been classified as Pathogenic. |