ClinVar Miner

Submissions for variant NM_172057.2(KCNH2):c.1760G>A (p.Trp587Ter) (rs794728399)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000631582 SCV000752664 pathogenic Long QT syndrome 2018-03-01 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp927*) in the KCNH2 gene. It is expected to result in an absent or disrupted protein product. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been reported in several individuals affected with Long QT syndrome or with suspected Long QT syndrome (PMID: 23158531, 19716085). Experimental studies have shown that this nonsense change affects potassium channel  function causing a reduction in current densitites (PMID: 19324319). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Loss-of-function variants in KCNH2 are known to be pathogenic (PMID: 19862833). For these reasons, this variant has been classified as Pathogenic.

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