ClinVar Miner

Submissions for variant NM_000219.5(KCNE1):c.292C>T (p.Arg98Trp) (rs199473362)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000619552 SCV000737536 likely pathogenic Cardiovascular phenotype 2017-06-06 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),In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
Biesecker Lab/Human Development Section,National Institutes of Health RCV000171560 SCV000050606 uncertain significance Long QT syndrome 2018-04-05 criteria provided, single submitter research
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000119088 SCV000153807 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:16922724;PMID:19907016). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.
Human Genome Sequencing Center Clinical Lab,Baylor College of Medicine RCV000709726 SCV000839963 pathogenic Long QT syndrome 5 2017-07-05 criteria provided, single submitter clinical testing This c.292C>T (p.Arg98Trp) variant in the KCNE1 gene has been reported in 6 individuals and one family from a cohort of 262 patients with long QT [PMID 10973849] and additional patients [PMID 16922724, 17341399]. Segregation of the variant with the disorder was observed in one additional family of 7 individuals, 2 of which were carrier for this variant [PMID 21070882]. Functional assays showed a modest effect of the variant on trafficking and current density [PMID 17341399]. This variant was reported in 2 heterozygous individuals from Europe and East-Asia ( Arginine at amino acid position 98 of the KCNE1 protein is highly conserved in mammals. While not validated for clinical use, computer-based algorithms SIFT and Polyphen-2 predict this p.Arg98Trp change to be deleterious. This variant thus classified as pathogenic.
Invitae RCV000171560 SCV000549144 uncertain significance Long QT syndrome 2016-05-30 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 98 of the KCNE1 protein (p.Arg98Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs199473362, ExAC 0.01%). This variant has been reported in individuals affected with long QT syndrome (PMID: 10973849, 16922724, 17341399), and sudden unexpected death (PMID: 21070882). ClinVar contains an entry for this variant (Variation ID: 132676). Experimental studies have shown that this missense has a mild effect on KCNE1 current and trafficking (PMID: 17341399, 19907016), but the clinical significance of this observation is uncertain. 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.

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