Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000811642 | SCV000951918 | uncertain significance | Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility to, 5 | 2023-12-09 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 575 of the CACNA1S protein (p.Leu575Phe). This variant is present in population databases (rs772213240, gnomAD 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: 655458). 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) performed at Invitae indicates that this missense variant is expected to disrupt CACNA1S protein function with a positive predictive value of 80%. 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. |
Gene |
RCV002462175 | SCV002756759 | uncertain significance | not provided | 2022-05-16 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Genome- |
RCV003453699 | SCV004179009 | uncertain significance | Malignant hyperthermia, susceptibility to, 5 | 2023-04-11 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV003453700 | SCV004179010 | uncertain significance | Thyrotoxic periodic paralysis, susceptibility to, 1 | 2023-04-11 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV003458542 | SCV004179011 | uncertain significance | Congenital myopathy 18 | 2023-04-11 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV003456149 | SCV004179012 | uncertain significance | Hypokalemic periodic paralysis, type 1 | 2023-04-11 | criteria provided, single submitter | clinical testing |