Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003102288 | SCV003308194 | pathogenic | Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility to, 5 | 2022-08-16 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg900 amino acid residue in CACNA1S. Other variant(s) that disrupt this residue have been observed in individuals with CACNA1S-related conditions (PMID: 21855088), which suggests that this may be a clinically significant amino acid residue. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on CACNA1S function (PMID: 34463712). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This missense change has been observed in individuals with clinical features of hypokalemic periodic paralysis (PMID: 19118277, 25213595, 26433613; Invitae). 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 serine, which is neutral and polar, at codon 900 of the CACNA1S protein (p.Arg900Ser). |
| Department of Neurology and Geriatrics, |
RCV002306242 | SCV002600037 | pathogenic | Hypokalemic periodic paralysis, type 1 | 2022-04-12 | no assertion criteria provided | research |