Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000170948 | SCV000223508 | uncertain significance | not provided | 2022-04-20 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function |
Invitae | RCV000465418 | SCV000541559 | uncertain significance | Brugada syndrome 8 | 2023-03-26 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 190789). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt HCN4 protein function. This variant has not been reported in the literature in individuals affected with HCN4-related conditions. This variant is present in population databases (rs761337460, gnomAD 0.01%). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 820 of the HCN4 protein (p.Gly820Arg). |
Ambry Genetics | RCV002426811 | SCV002731616 | uncertain significance | Cardiovascular phenotype | 2022-12-16 | criteria provided, single submitter | clinical testing | The p.G820R variant (also known as c.2458G>A), located in coding exon 8 of the HCN4 gene, results from a G to A substitution at nucleotide position 2458. The glycine at codon 820 is replaced by arginine, 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 tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |