Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV001841005 | SCV001354464 | uncertain significance | Cardiac arrhythmia | 2023-01-10 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with tryptophan at codon 883 of the KCNH2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with KCNH2-related disorders in the literature. This variant has been identified in 8/281260 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
Invitae | RCV001219456 | SCV001391396 | uncertain significance | Long QT syndrome | 2024-01-09 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 883 of the KCNH2 protein (p.Arg883Trp). This variant is present in population databases (rs201765446, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with KCNH2-related conditions. ClinVar contains an entry for this variant (Variation ID: 925591). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. |
Gene |
RCV001572412 | SCV001797044 | uncertain significance | not provided | 2019-04-16 | criteria provided, single submitter | clinical testing | In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge |
Ambry Genetics | RCV002429829 | SCV002743725 | uncertain significance | Cardiovascular phenotype | 2023-07-20 | criteria provided, single submitter | clinical testing | The p.R883W variant (also known as c.2647C>T), located in coding exon 11 of the KCNH2 gene, results from a C to T substitution at nucleotide position 2647. The arginine at codon 883 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Fulgent Genetics, |
RCV002497655 | SCV002791800 | uncertain significance | Short QT syndrome type 1; Long QT syndrome 2 | 2021-09-07 | criteria provided, single submitter | clinical testing |