ClinVar Miner

Submissions for variant NM_172057.2(KCNH2):c.1489G>A (p.Asp497Asn) (rs199473005)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Medical Genetics Ghent,University of Ghent RCV000240628 SCV000299240 likely pathogenic Long QT syndrome 2 2016-01-01 criteria provided, single submitter clinical testing
Invitae RCV000631627 SCV000752710 pathogenic Long QT syndrome 2017-12-26 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 837 of the KCNH2 protein (p.Asp837Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is not present in population databases (rs199473005, ExAC no frequency). This variant has been reported in indiviudals affected with Long QT syndrome  (PMID: 26669661, 19841300). ClinVar contains an entry for this variant (Variation ID: 67405). A different missense substitution at this codon (p.Asp837Gly) has been determined to be pathogenic (Invitae database). This suggests that the aspartic acid residue is critical for KCNH2 protein function and that other missense substitutions at this position may also be pathogenic. For these reasons, this variant has been classified as Pathogenic.
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000058129 SCV000089649 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:19841300). 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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