Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000522132 | SCV000619936 | uncertain significance | not provided | 2017-08-16 | criteria provided, single submitter | clinical testing | The R419H variant in the CACNA1S gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. This variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R419H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret R419H as a variant of uncertain significance. |
Invitae | RCV000811193 | SCV000951447 | uncertain significance | Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility to, 5 | 2021-08-28 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with histidine at codon 419 of the CACNA1S protein (p.Arg419His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs370861322, ExAC 0.006%). This variant has not been reported in the literature in individuals affected with CACNA1S-related conditions. ClinVar contains an entry for this variant (Variation ID: 451262). 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: "Probably 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. |
Genome- |
RCV003456085 | SCV004179164 | uncertain significance | Malignant hyperthermia, susceptibility to, 5 | 2023-04-11 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV003456086 | SCV004179165 | uncertain significance | Thyrotoxic periodic paralysis, susceptibility to, 1 | 2023-04-11 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV003458449 | SCV004179166 | uncertain significance | Congenital myopathy 18 | 2023-04-11 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV003449493 | SCV004179167 | uncertain significance | Hypokalemic periodic paralysis, type 1 | 2023-04-11 | criteria provided, single submitter | clinical testing |