ClinVar Miner

Submissions for variant NM_172057.2(KCNH2):c.2231C>T (p.Pro744Leu) (rs762510312)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000535906 SCV000627480 uncertain significance Long QT syndrome 2018-10-14 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 1084 of the KCNH2 protein (p.Pro1084Leu). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs762510312, ExAC 0.01%) but 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. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000620231 SCV000737439 uncertain significance Cardiovascular phenotype 2017-11-27 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence

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