ClinVar Miner

Submissions for variant NM_172056.2(KCNH2):c.1280A>G (p.Tyr427Cys) (rs199472897)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Agnes Ginges Centre for Molecular Cardiology,Centenary Institute RCV000584803 SCV000692514 likely pathogenic Long QT syndrome 1 2017-03-16 criteria provided, single submitter research The KCNH2 Tyr427Cys variant is located in the Transmembrane/ S1 domain. It has been reported in 2 long QT probands and was absent from 1300 controls (Itoh H, et al., 2016; Kapplinger, et al., 2009). The variant is absent in the 1000 genomes project (http://www.1000genomes.org/), as well as the Exome Aggregation Consortium dataset (http://exac.broadinstitute.org/). We have identified this variant in one long QT proband with no family history of disease or SCD. Interestingly, different rare variants at this position (Tyr427Ser and Tyr427His) have also been reported in long QT individuals, suggesting that an amino acid substitution at this site may not be tolerated. Computational tools SIFT, MutationTaster, and PolyPhen-2 predict this variant to have a deleterious effect. The variant was discussed at our multidisciplinary pathogenicity meeting and it was agreed based on the above evidence that it should be considered as "likely pathogenic".
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000057886 SCV000089406 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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