Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000698565 | SCV000827235 | uncertain significance | Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility to, 5 | 2018-05-22 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine with proline at codon 520 of the CACNA1S protein (p.Thr520Pro). The threonine residue is moderately conserved and there is a small physicochemical difference between threonine and proline. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with CACNA1S-related disease. 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. |