ClinVar Miner

Submissions for variant NM_172056.2(KCNH2):c.865G>A (p.Glu289Lys) (rs199472880)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000202899 SCV000257649 uncertain significance Long QT syndrome 2 2015-06-25 criteria provided, single submitter clinical testing
Invitae RCV000460639 SCV000543436 uncertain significance Long QT syndrome 2018-09-19 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 289 of the KCNH2 protein (p.Glu289Lys). The glutamic acid residue is weakly conserved and there is a small physicochemical difference between glutamic acid and lysine. While this variant is not present in population databases (rs199472880), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been reported in an individual affected with Romano-Ward syndrome (PMID: 19862833). ClinVar contains an entry for this variant (Variation ID: 67535). Experimental studies have shown that this missense change results in normal KCNH2 protein expression in cell culture (PMID: 26958806). In summary, this variant is a rare missense change that is not expected to affect 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.
Ambry Genetics RCV000619478 SCV000736437 uncertain significance Cardiovascular phenotype 2017-07-20 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV000460639 SCV000740342 uncertain significance Long QT syndrome 2017-05-29 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000765945 SCV000897366 uncertain significance Short QT syndrome 1; Long QT syndrome 2 2018-10-31 criteria provided, single submitter clinical testing
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000058264 SCV000089784 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:19862833). 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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