ClinVar Miner

Submissions for variant NM_172056.2(KCNH2):c.1603G>A (p.Val535Met) (rs375872367)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000459974 SCV000543413 uncertain significance Long QT syndrome 2016-10-04 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 535 of the KCNH2 protein (p.Val535Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. This variant is present in population databases (rs375872367, ExAC 0.002%). This variant has been reported in two related individuals affected with long QT syndrome (PMID: 22173492). ClinVar contains an entry for this variant (Variation ID: 161256). This variant identified in the KCNH2 gene is located in the transmembrane S4 region of the resulting protein (PMID: 19841300, 25348405). For more information about the location of this variant, please visit Experimental studies have shown that this missense change leads to a negative inactivation shift with slowed recovery of the KCNH2 channel in vitro, but the clinical significance of this observation is uncertain (PMID: 22173492). In summary, this variant is a rare missense change with uncertain impact on protein function. It has been reported in both the population and affected individuals, but 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 RCV000622193 SCV000737695 uncertain significance Cardiovascular phenotype 2016-09-07 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
CSER _CC_NCGL, University of Washington RCV000148538 SCV000190251 uncertain significance Long QT syndrome 2 2014-06-01 no assertion criteria provided research

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