ClinVar Miner

Submissions for variant NM_000238.4(KCNH2):c.3365dup (p.Ala1124fs)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001216294 SCV001388084 likely pathogenic Long QT syndrome 2019-06-10 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the KCNH2 gene (p.Ala1124Glyfs*146). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 36 amino acids of the KCNH2 protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with long QT syndrome (PMID: 15572050, Invitae). This variant is also known in the literature as 1122fs/147. This variant has been reported to affect KCNH2 protein function (PMID: 15572050). 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.
GeneDx RCV001544857 SCV001764072 uncertain significance not provided 2021-05-21 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); Frameshift variant predicted to result in protein truncation as the last 36 amino acids are replaced with 145 different amino acids, although loss-of-function variants have not been reported downstream of this position in the protein; This variant is associated with the following publications: (PMID: 15572050)

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