Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001035425 | SCV001198752 | uncertain significance | Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility to, 5 | 2021-08-31 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with arginine at codon 978 of the CACNA1S protein (p.Gly978Arg). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs760596943, ExAC 0.01%). This variant has not been reported in the literature in individuals affected with CACNA1S-related conditions. 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 tolerated. 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. |