Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Baylor Genetics | RCV000191067 | SCV000245459 | uncertain significance | Hypokalemic periodic paralysis, type 1 | 2023-06-27 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001376984 | SCV001574200 | likely pathogenic | Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility to, 5 | 2022-06-20 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 209137). Disruption of this splice site has been observed in individual(s) with clinical features of hypokalemic periodic paralysis (PMID: 26633545). This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 27 of the CACNA1S gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CACNA1S are known to be pathogenic (PMID: 26247046, 28012042). |