Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Athena Diagnostics Inc | RCV000518061 | SCV000612604 | pathogenic | not provided | 2014-06-02 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000693727 | SCV000821608 | pathogenic | Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility to, 5 | 2021-10-04 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg1239 amino acid residue in CACNA1S. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7847370, 17418573, 19225109). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 17624). This missense change has been observed in individual(s) with hypokalemic periodic paralysis (PMID: 8004673, 15716625, 18162704, 18229654). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with glycine at codon 1239 of the CACNA1S protein (p.Arg1239Gly). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and glycine. |
Gene |
RCV000518061 | SCV001780892 | pathogenic | not provided | 2021-07-20 | criteria provided, single submitter | clinical testing | Recurrent variant associated with hypokalemic periodic paralysis (Matthews et al., 2009); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed in large population cohorts (Lek et al., 2016) This variant is associated with the following publications: (PMID: 15221887, 26252573, 15711422, 19779499, 18229654, 15716625, 19118277, 20301512, 11353725, 8004673, 21891927) |
Genome- |
RCV003450646 | SCV004177655 | pathogenic | Malignant hyperthermia, susceptibility to, 5 | 2023-04-11 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV000019191 | SCV004177656 | pathogenic | Hypokalemic periodic paralysis, type 1 | 2023-04-11 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000019191 | SCV000039479 | pathogenic | Hypokalemic periodic paralysis, type 1 | 1994-06-17 | no assertion criteria provided | literature only | |
Gene |
RCV000019191 | SCV000040411 | not provided | Hypokalemic periodic paralysis, type 1 | no assertion provided | literature only |