Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002448421 | SCV002735637 | uncertain significance | Cardiovascular phenotype | 2018-02-09 | criteria provided, single submitter | clinical testing | The p.R784P variant (also known as c.2351G>C), located in coding exon 9 of the KCNH2 gene, results from a G to C substitution at nucleotide position 2351. The arginine at codon 784 is replaced by proline, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV003101752 | SCV003330431 | uncertain significance | Long QT syndrome | 2022-03-16 | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with KCNH2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 784 of the KCNH2 protein (p.Arg784Pro). |