ClinVar Miner

Submissions for variant NM_172056.2(KCNH2):c.1801G>A (p.Gly601Ser) (rs199472936)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV000208241 SCV000263975 pathogenic Long QT syndrome 2 2014-12-29 criteria provided, single submitter clinical testing
Invitae RCV000233419 SCV000283967 pathogenic Long QT syndrome 2018-03-19 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 601 of the KCNH2 protein (p.Gly601Ser). The glycine residue is moderately conserved and there is a small physicochemical difference between glycine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with long QT syndrome (LQTS), segregating with the disease in one LQTS family (PMID: 9452080, 10862094, 18441445, 18752142, 19841300). ClinVar contains an entry for this variant (Variation ID: 67279). This variant identified in the KCNH2 gene is located in the transmembrane spanning S5/pore region of the resulting protein (PMID: 19841300, 25348405). For more information about the location of this variant, please visit www.invitae.com/KCNH2-topology. Experimental studies have shown that this missense change has a drastic effect on protein trafficking and is not able to functionally rescue for the loss of KCNH2 in an experimental animal system (PMID: 10226095, 12775586, 23303164). In summary, this variant has been reported in affected individuals, segregates with the disease in one family, and has been shown to affect protein function. For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000619597 SCV000737559 likely pathogenic Cardiovascular phenotype 2016-12-08 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation,Deficient protein function in appropriate functional assay(s),Rarity in general population databases (dbsnp, esp, 1000 genomes)
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000057995 SCV000089515 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:9452080;PMID:10483966;PMID:10862094;PMID:16432067;PMID:18441445;PMID:18752142;PMID:19716085;PMID:19841300;PMID:21490315;PMID:21573751;PMID:10226095;PMID:11741928). 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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