ClinVar Miner

Submissions for variant NM_172057.2(KCNH2):c.2144G>A (p.Arg715Gln) (rs41307270)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000181743 SCV000234046 likely benign not specified 2015-03-12 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics RCV000246544 SCV000319531 uncertain significance Cardiovascular phenotype 2016-07-13 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Illumina Clinical Services Laboratory,Illumina RCV000398697 SCV000467505 uncertain significance Long QT syndrome 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000398697 SCV000834399 uncertain significance Long QT syndrome 2018-03-05 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 1055 of the KCNH2 protein (p.Arg1055Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs41307270, ExAC 0.1%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been reported in an individual affected with hypertrophic cardiomyopathy (PMID: 25351510) and has also been reported in unaffected individuals (PMID: 16487223). ClinVar contains an entry for this variant (Variation ID: 67475). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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 RCV000058204 SCV000089724 not provided not provided no assertion provided literature only This variant has been reported in the following publications (PMID:16487223).

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