ClinVar Miner

Submissions for variant NM_172057.2(KCNH2):c.2083C>T (p.Arg695Trp) (rs199473543)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000473177 SCV000543412 uncertain significance Long QT syndrome 2018-07-25 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 1035 of the KCNH2 protein (p.Arg1035Trp). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a KCNH2-related disease. However, it has been reported in a healthy control individual (PMID: 14661677). ClinVar contains an entry for this variant (Variation ID: 67468). 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: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000058196 SCV000089716 not provided not provided no assertion provided literature only This variant has been reported in the following publications (PMID:14661677;PMID:19841300).

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