Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV001841042 | SCV001355650 | uncertain significance | Cardiac arrhythmia | 2020-01-17 | criteria provided, single submitter | clinical testing | This missense variant replaces glycine with arginine at codon 970 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). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has not been identified 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. |
| Ambry Genetics | RCV002436759 | SCV002750944 | uncertain significance | Cardiovascular phenotype | 2022-02-22 | criteria provided, single submitter | clinical testing | The p.G970R variant (also known as c.2908G>A), located in coding exon 12 of the KCNH2 gene, results from a G to A substitution at nucleotide position 2908. The glycine at codon 970 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is 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. |