ClinVar Miner

Submissions for variant NM_172056.2(KCNH2):c.934C>T (p.Arg312Cys) (rs199472885)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000171561 SCV000050607 uncertain significance Long QT syndrome 2018-04-05 criteria provided, single submitter research
Invitae RCV000171561 SCV000283990 uncertain significance Long QT syndrome 2018-10-19 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 312 of the KCNH2 protein (p.Arg312Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs199472885, ExAC 0.02%). This variant has been reported in an individual affected with long QT syndrome (PMID: 10973849) and in an individual who presented with sinus bradycardia, first-degree atrioventricular block, moderate mitral regurgitation and impaired left ventricular relaxation on ECHO, and who had a family history of sudden death (PMID: 23861362). ClinVar contains an entry for this variant (Variation ID: 67547). This variant identified in the KCNH2 gene is located in the cytoplasmic N-terminal 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. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, this variant has been reported in two affected individuals and has an uncertain impact on protein function. For these reasons, this change has been classified as a Variant of Uncertain Significance.
Fulgent Genetics,Fulgent Genetics RCV000515393 SCV000611203 pathogenic Short QT syndrome 1; Long QT syndrome 2 2017-05-18 criteria provided, single submitter clinical testing
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000058276 SCV000089796 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:10973849;PMID:15051636;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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