Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000464288 | SCV000543448 | uncertain significance | Long QT syndrome | 2019-06-22 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.Pro72 amino acid residue in KCNH2. Other variant(s) that disrupt this residue have been determined to be pathogenic  (PMID: 11854117, 25417810). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. This variant has been reported in the literature in one individual affected with long QT syndrome (PMID: 20960620). ClinVar contains an entry for this variant (Variation ID: 67369). This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with arginine at codon 72 of the KCNH2 protein (p.Pro72Arg). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and arginine. |
Cardiovascular Biomedical Research Unit, |
RCV000058089 | SCV000089609 | 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:20960616). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory. |