ClinVar Miner

Submissions for variant NM_172057.2(KCNH2):c.2213A>G (p.Tyr738Cys) (rs199473029)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000455396 SCV000539445 uncertain significance not specified 2016-07-26 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Reported in 1 LQT proband (PMID 19716085), functional study (PMID 25417810) shows this variant does not impact trafficking
Invitae RCV000684931 SCV000812394 uncertain significance Long QT syndrome 2018-06-04 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with cysteine at codon 1078 of the KCNH2 protein (p.Tyr1078Cys). The tyrosine residue is moderately conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual reffered for LQTS genetic testing, however it is not known if this individual was affected with KCNH2-related conditions (PMID: 19716085). ClinVar contains an entry for this variant (Variation ID: 67483). This variant identified in the KCNH2 gene is located in the cytoplasmic C-terminal region of the resulting protein (PMID: 19841300, 25348405). However, experimental studies have shown that this missense change does not have an effect on trafficking the KCNH2 protein to the plasma membrane (PMID: 25417810). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000058212 SCV000089732 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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