Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001306370 | SCV001495740 | uncertain significance | Brugada syndrome 8 | 2022-07-26 | 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: 1008953). This variant has not been reported in the literature in individuals affected with HCN4-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamine, which is neutral and polar, with lysine, which is basic and polar, at codon 977 of the HCN4 protein (p.Gln977Lys). |
| Ambry Genetics | RCV002437044 | SCV002748768 | uncertain significance | Cardiovascular phenotype | 2021-09-07 | criteria provided, single submitter | clinical testing | The p.Q977K variant (also known as c.2929C>A), located in coding exon 8 of the HCN4 gene, results from a C to A substitution at nucleotide position 2929. The glutamine at codon 977 is replaced by lysine, an amino acid with similar properties. This amino acid position is conserved. 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. |