ClinVar Miner

Submissions for variant NM_172057.2(KCNH2):c.1745G>A (p.Arg582Gln) (rs199473439)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000471859 SCV000543423 uncertain significance Long QT syndrome 2018-04-11 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 922 of the KCNH2 protein (p.Arg922Gln). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and glutamine. While this variant is not present in population databases (rs199473439), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been reported in the literature in one individual referred for long QT syndrome genetic testing (PMID: 19716085). ClinVar contains an entry for this variant (Variation ID: 67436). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: (SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). The glutamine amino acid residue is also found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies. This variant identified in the KCNH2 gene is located in the cytoplasmic C-terminal region of the resulting protein (PMID: 19841300, 25348405), but it is unclear how this variant impacts the function of this protein. In summary, this variant is a rare missense change with uncertain impact on protein function. It has been reported in both the population and individuals suspected to be affected, but the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000058162 SCV000089682 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:19716085). 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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