Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000497854 | SCV000590339 | uncertain significance | not provided | 2017-06-14 | criteria provided, single submitter | clinical testing | The P457L variant in the CACNA1S gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The P457L variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The P457L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret P457L as a variant of uncertain significance. |
Invitae | RCV000651230 | SCV000773081 | uncertain significance | Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility to, 5 | 2023-07-29 | criteria provided, single submitter | clinical testing | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on CACNA1S protein function. ClinVar contains an entry for this variant (Variation ID: 432592). This variant has not been reported in the literature in individuals affected with CACNA1S-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 457 of the CACNA1S protein (p.Pro457Leu). |
Fulgent Genetics, |
RCV002481589 | SCV002792220 | uncertain significance | Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility to, 5; Thyrotoxic periodic paralysis, susceptibility to, 1 | 2021-09-15 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV003456082 | SCV004179129 | uncertain significance | Malignant hyperthermia, susceptibility to, 5 | 2023-04-11 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV003456083 | SCV004179130 | uncertain significance | Thyrotoxic periodic paralysis, susceptibility to, 1 | 2023-04-11 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV003458444 | SCV004179131 | uncertain significance | Congenital myopathy 18 | 2023-04-11 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV003449393 | SCV004179132 | uncertain significance | Hypokalemic periodic paralysis, type 1 | 2023-04-11 | criteria provided, single submitter | clinical testing |