Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000695220 | SCV000823705 | pathogenic | Long QT syndrome | 2025-01-15 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 3 of the KCNQ1 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 KCNQ1 are known to be pathogenic (PMID: 9323054, 19862833). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with Jervell and Lange-Nielsen syndrome (PMID: 22629021). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 573523). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
Juno Genomics, |
RCV004796281 | SCV005418165 | likely pathogenic | Atrial fibrillation, familial, 3; Long QT syndrome 1; Jervell and Lange-Nielsen syndrome 1; Short QT syndrome type 2 | criteria provided, single submitter | clinical testing | PVS1+PM2_Supporting |