Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003531902 | SCV004294707 | likely pathogenic | Long QT syndrome | 2023-09-28 | 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. Studies have shown that disruption of this splice site is associated with altered splicing resulting in multiple RNA products (PMID: 21057041). ClinVar contains an entry for this variant (Variation ID: 14438). Disruption of this splice site has been observed in individuals with long QT syndrome (PMID: 10086971; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 10 of the KCNH2 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 KCNH2 are known to be pathogenic (PMID: 10973849, 19862833). |
| Gene |
RCV004719649 | SCV005325352 | pathogenic | not provided | 2024-01-02 | criteria provided, single submitter | clinical testing | 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; Not observed at significant frequency in large population cohorts (gnomAD); Functional in vitro studies of hERG transfected HEK293 cells demonstrated that this variant abolishes the normal splicing and disrupts channel trafficking (PMID: 21057041); This variant is associated with the following publications: (PMID: 21057041, 10086971) |
| OMIM | RCV000015519 | SCV000035784 | pathogenic | Long QT syndrome 1/2, digenic | 1999-03-23 | no assertion criteria provided | literature only |