ClinVar Miner

Submissions for variant NM_172056.2(KCNH2):c.1325C>T (p.Ala442Val) (rs1554426225)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000536145 SCV000627420 uncertain significance Long QT syndrome 2017-06-12 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 442 of the KCNH2 protein (p.Ala442Val). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and valine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with a KCNH2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, this variant has uncertain impact on KCNH2 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000768002 SCV000898771 uncertain significance Short QT syndrome 1; Long QT syndrome 2 2018-08-31 criteria provided, single submitter clinical testing KCNH2 NM_000238.3 exon 6 p.Ala442Val (c.1325C>T): This variant has not been reported in the literature and is not present in large control databases. This variant is present in ClinVar (Variation ID:456885). Evolutionary conservation and computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain._x000D_

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