ClinVar Miner

Submissions for variant NM_172056.2(KCNH2):c.243G>C (p.Gln81His) (rs199472849)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000702044 SCV000830873 uncertain significance Long QT syndrome 2018-03-07 criteria provided, single submitter clinical testing This sequence change replaces glutamine with histidine at codon 81 of the KCNH2 protein (p.Gln81His). The glutamine residue is weakly conserved and there is a small physicochemical difference between glutamine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an infant affected with sudden death after a history of febrile convulsions (PMID: 20167303). ClinVar contains an entry for this variant (Variation ID: 67399). 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.
RBHT Clinical Genetics and Genomics Laboratory,Royal Brompton and Harefield NHS Foundation Trust RCV000714904 SCV000845657 uncertain significance Long QT syndrome, LQT1 subtype 2017-09-08 criteria provided, single submitter clinical testing This variant has not been detected in control populations (ExAC), and has been reported once in the literature, in a 21 month old who died suddenly, it was also detected in the healthy father (Gladding et al 2010 Heart Rhythm 7(4):481-6) . The variant is located in the N-terminus region, which is a hotspot for mutations. The affecte amino acid is highly conserved, how in silico tools offer conflicting evidence as to the damaging effect on protein function
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000058121 SCV000089641 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:20167303). 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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