Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003103779 | SCV000548681 | likely pathogenic | Catecholaminergic polymorphic ventricular tachycardia 1 | 2022-03-18 | 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: 408869). This variant has not been reported in the literature in individuals affected with CASQ2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 1 of the CASQ2 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 CASQ2 are known to be pathogenic (PMID: 12386154). |
| Ambry Genetics | RCV000618299 | SCV000737604 | likely pathogenic | Cardiovascular phenotype | 2019-02-14 | criteria provided, single submitter | clinical testing | The c.235-2A>G intronic variant results from an A to G substitution two nucleotides upstream from coding exon 2 in the CASQ2 gene. This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native splice acceptor site; however, direct evidence is unavailable. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as likely pathogenic. |
| Gene |
RCV001546335 | SCV001765832 | likely pathogenic | not provided | 2020-12-16 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Reported in ClinVar as a likely pathogenic variant (ClinVar Variant ID# 408869; Landrum et al., 2016); Not observed in large population cohorts (Lek et al., 2016); Canonical splice site variant predicted to result in a null allele in a gene for which loss-of-function is a known mechanism of disease |
| Genome- |
RCV003338598 | SCV004048971 | likely pathogenic | Catecholaminergic polymorphic ventricular tachycardia 2 | 2023-04-11 | criteria provided, single submitter | clinical testing |