ClinVar Miner

Submissions for variant NM_172056.2(KCNH2):c.164C>T (p.Ser55Leu) (rs199472844)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000182049 SCV000234352 pathogenic not provided 2018-07-09 criteria provided, single submitter clinical testing The S55L pathogenic variant in the KCNH2 gene has been reported in association with LQTS and was reported to segregate with disease in four related individuals with LQTS and a family history of sudden arrhythmic death syndrome (SADS) (Tester et al., 2005; Behr et al., 2008). Additionally, the S55L variant is not observed in large population cohorts (Lek et al., 2016). The S55L variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This variant is located in the PAS domain which is thought to participate in the regulation of channel function (Harley et al., 2012). In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Furthermore, functional studies show that the S55L variant causes deficient protein trafficking (Anderson et al., 2014).
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000057933 SCV000089453 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:15840476;PMID:18508782). 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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