ClinVar Miner

Submissions for variant NM_172056.2(KCNH2):c.1685A>G (p.His562Arg) (rs199472922)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000544355 SCV000627432 uncertain significance Long QT syndrome 2017-04-01 criteria provided, single submitter clinical testing This sequence change replaces histidine with arginine at codon 562 of the KCNH2 protein (p.His562Arg). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and arginine. This variant is not present in population databases (ExAC no frequency). This variant was reported in a family with long QT syndrome (PMID: 25819988) and in individuals referred for genetic long QT testing (PMID: 19716085). ClinVar contains an entry for this variant (Variation ID: 67232). Experimental studies have shown that this missense change leads to defective protein trafficking (PMID: 25417810). This variant identified in the KCNH2 gene is located in the transmembrane S5 region of the resulting protein (PMID: 19841300, 25348405). For more information about the location of this variant, please visit www.invitae.com/KCNH2-topology. It is unclear how this variant impacts the function of this protein. In summary, this variant is a rare missense change with a deleterious affect on protein function. While it is absent from the population and reported in affected individuals, the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000057943 SCV000089463 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:19716085). 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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