ClinVar Miner

Submissions for variant NM_181798.1(KCNQ1):c.651+1G>A (rs397508070)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000182161 SCV000234464 likely pathogenic not provided 2019-01-04 criteria provided, single submitter clinical testing The c.1032+1 G>A likely pathogenic variant in the KCNQ1 gene has been reported in association with LQTS (Berge et al., 2008; Kapplinger et al., 2009; Shigemizu et al., 2015). This variant destroys the canonical splice donor site in intron 7 and is predicted to cause abnormal gene splicing. The c.1032+1 G>A variant is predicted to lead to either an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. Other splice site variants in the KCNQ1 gene have been reported in HGMD in association with LQTS (Stenson et al., 2014). Furthermore, the c.1032+1 G>A variant is not observed in large population cohorts (Lek et al., 2016). In summary, c.1032+1 G>A in the KCNQ1 gene is interpreted as a likely pathogenic variant.
Invitae RCV000190169 SCV001576508 likely pathogenic Long QT syndrome 2019-12-23 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 7 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 individual(s) with clinical features of long QT syndrome (PMID: 16244680, 16244680, 19716085). ClinVar contains an entry for this variant (Variation ID: 52937). 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.
Medical Research Institute,Tokyo Medical and Dental University RCV000190169 SCV000222019 likely pathogenic Long QT syndrome no assertion criteria provided research

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