ClinVar Miner

Submissions for variant NM_000218.3(KCNQ1):c.1515-2_1515-1del

dbSNP: rs1564886323
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000698644 SCV000827324 likely pathogenic Long QT syndrome 2023-10-18 criteria provided, single submitter clinical testing This sequence change affects a splice site in intron 11 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 clinical features of KCNQ1-related conditions (PMID: 19716085; Invitae). This variant is also known as 1515-2 del AG. ClinVar contains an entry for this variant (Variation ID: 576205). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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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