ClinVar Miner

Submissions for variant NM_181798.1(KCNQ1):c.1134-2_1134-1del (rs1564886323)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000698644 SCV000827324 likely pathogenic Long QT syndrome 2019-08-24 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 11 of the KCNQ1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual referred for long QT testing (PMID: 19716085). This variant is also known as 1515-2 del AG in the literature. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Donor and acceptor splice site variants 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). 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000698644 SCV000917562 likely pathogenic Long QT syndrome 2017-12-26 criteria provided, single submitter clinical testing Variant summary: The KCNQ1 c.1515-2_1515-1delAG variant involves the deletion of two intronic nucleotides that represent the canonical splice site at the intron/exon junction. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict a loss of normal splicing due to the deletion, as well as a disruption of ESE sites at the locus. However, these predictions have yet to be confirmed by functional studies. This variant is absent in 246228 control chromosomes but was identified in a patient suspected of Long QT syndrome (Kapplinger_2009). Taken together, this variant is classified as likely pathogenic.

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