ClinVar Miner

Submissions for variant NM_172056.2(KCNH2):c.2162C>T (p.Pro721Leu) (rs199472986)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000458802 SCV000543427 likely pathogenic Long QT syndrome 2018-05-29 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 721 of the KCNH2 protein (p.Pro721Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (rs199472986, ExAC no frequency). This variant has been reported in at least one individual affected with long QT syndrome (PMID: 15840476, 19841300, 22949429, 26669661). ClinVar contains an entry for this variant (Variation ID: 67371). Experimental studies have shown that this missense change leads to a trafficking-deficient KCNH2 protein that is unable to be corrected in vitro (PMID: 25417810). In summary, this variant is absent from population databases, has been observed in at least one patient with long QT syndrome, and has been shown to have a deleterious functional effect. In the absence of confirmed segregation evidence, at this time this variant has been classified as Likely Pathogenic.
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000058091 SCV000089611 not provided Congenital long QT syndrome no assertion provided literature only This variant has been reported as associated with Long QT syndrome in the following publications (PMID:15840476;PMID:19841300). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.

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