Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000693253 | SCV000821113 | uncertain significance | Brugada syndrome 8 | 2023-12-18 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1024 of the HCN4 protein (p.Gly1024Val). This variant is present in population databases (rs775491475, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with HCN4-related conditions. ClinVar contains an entry for this variant (Variation ID: 571974). 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 with a negative predictive value of 95%. 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. |
Ambry Genetics | RCV002319557 | SCV002608665 | uncertain significance | Cardiovascular phenotype | 2022-07-29 | criteria provided, single submitter | clinical testing | The p.G1024V variant (also known as c.3071G>T), located in coding exon 8 of the HCN4 gene, results from a G to T substitution at nucleotide position 3071. The glycine at codon 1024 is replaced by valine, an amino acid with dissimilar 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. |