ClinVar Miner

Submissions for variant NM_172056.2(KCNH2):c.172G>A (p.Glu58Lys) (rs199473413)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000472868 SCV000543435 likely pathogenic Long QT syndrome 2016-09-05 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 58 of the KCNH2 protein (p.Glu58Lys). The glutamic acid residue is weakly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is not present in population databases (rs199473413, ExAC no frequency). This variant has been reported in several individuals affected with long QT syndrome (PMID: 11222472, 19695459, Invitae database). ClinVar contains an entry for this variant (Variation ID: 67254). This variant identified in the KCNH2 gene is located in the cytoplasmic PAS region of the resulting protein (PMID: 19841300). Experimental studies have shown that this missense change leads to defective protein trafficking (PMID: 25417810). In summary, this variant is absent from population databases, has been observed in affected individuals, and has a deleterious effect on protein function. In the absence of confirmed segregation data, at this time this variant has been classified as Likely Pathogenic.
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000057966 SCV000089486 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:11222472). 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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