ClinVar Miner

Submissions for variant NM_172056.2(KCNH2):c.1689G>A (p.Trp563Ter) (rs199473517)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000631644 SCV000752727 pathogenic Long QT syndrome 2017-10-24 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp563*) in the KCNH2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with KCNH2-related disease. Loss-of-function variants in KCNH2 are known to be pathogenic (PMID: 19862833). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000760331 SCV000890187 pathogenic not provided 2018-06-06 criteria provided, single submitter clinical testing The W563X variant in the KCNH2 gene has been reported in one family with LQTS (Itoh et al., 2016). The W563X variant is predicted to cause loss of normal protein function either by protein truncation or nonsense-mediated mRNA decay. Other nonsense variants in the KCNH2 gene have been reported in Human Gene Mutation Database in association with LQTS (Stenson et al., 2014). Furthermore, the W563X variant is not observed in large population cohorts (Lek et al., 2016). In summary, W563X in the KCNH2 gene is interpreted as a pathogenic variant.

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