Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000804308 | SCV000944211 | uncertain significance | Brugada syndrome 8 | 2023-06-30 | 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. 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. ClinVar contains an entry for this variant (Variation ID: 649388). This variant has not been reported in the literature in individuals affected with HCN4-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.01%). This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1034 of the HCN4 protein (p.Pro1034Thr). |
| Ambry Genetics | RCV002325557 | SCV002605918 | uncertain significance | Cardiovascular phenotype | 2022-03-08 | criteria provided, single submitter | clinical testing | The p.P1034T variant (also known as c.3100C>A), located in coding exon 8 of the HCN4 gene, results from a C to A substitution at nucleotide position 3100. The proline at codon 1034 is replaced by threonine, an amino acid with highly similar properties. This amino acid position is not well 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. |