ClinVar Miner

Submissions for variant NM_172056.2(KCNH2):c.1745G>T (p.Arg582Leu) (rs199473426)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001377677 SCV001575069 likely pathogenic Long QT syndrome 2020-03-25 criteria provided, single submitter clinical testing This sequence change replaces arginine with leucine at codon 582 of the KCNH2 protein (p.Arg582Leu). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of long QT syndrome (PMID: 16414944, 18441445, Invitae). ClinVar contains an entry for this variant (Variation ID: 67258). This variant has been reported to affect KCNH2 protein function (PMID: 25417810, 21376840). This variant disrupts the p.Arg582 amino acid residue in KCNH2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10220144, 22949429, 12566525, 18441445, 21350584, 21376840). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000057971 SCV000089491 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:16414944). 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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