ClinVar Miner

Submissions for variant NM_172056.2(KCNH2):c.215C>T (p.Pro72Leu) (rs199473421)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000181938 SCV000234241 pathogenic not provided 2015-02-12 criteria provided, single submitter clinical testing The Pro72Leu mutation in the KCNH2 gene has been reported previously in association with LQTS (Kapplinger JD et al., 2009). Kapplinger et al. (2009) identified Pro72Leu in one patient with LQTS, and did not observe the mutation in more than 2,600 control alleles of varying ethnic backgrounds. Furthermore, the Pro72Leu mutation was not observed in approximately 6,400 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Mutations in the same residue (Pro72Arg, Pro72Gln) and nearby residues (His70Arg, His70Asn, Gly71Arg, Thr74Arg, Thr74Met, Thr74Pro) have been reported in association with LQTS, further supporting the functional importance of this residue and this region of the protein. Lastly, Pro72Leu results in a semi-conservative amino acid change, resulting in the loss of a sterically constrained Proline residue at a position that is class conserved in mammals. The variant is found in LQT panel(s).
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000058090 SCV000089610 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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