Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000429479 | SCV000515843 | pathogenic | not provided | 2015-03-19 | criteria provided, single submitter | clinical testing | The G820R variant in the KCNH2 gene has been reported in at least two unrelated individuals withLQTS and was absent in <1,300 healthy control individuals (Tester D et al., 2005; Giudicessi J et al.,2012). In addition, G820R was not observed in approximately 6,500 individuals of Europeanand African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a commonbenign variant in these populations. G820R results in a non-conservative amino acid substitution at aposition that is conserved in mammalian species. Consequently, In silico analysis predicts this variant isprobably damaging to the protein structure/function. Furthermore, a variant in the same residue (G820E)and in nearby residues (S818L, S818P, V822M, R823W) have been reported in the HumanGene Mutation Database in association with LQTS (Stenson P et al., 2014), further supporting thefunctional importance of this residue and region of the protein. In summary, G820R in the KCH2 gene is interpreted as a pathogenic variant. |
Cardiovascular Biomedical Research Unit, |
RCV000058124 | SCV000089644 | 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:19841300). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory. |