Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001304652 | SCV001493945 | uncertain significance | Brugada syndrome 8 | 2022-08-03 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 663 of the HCN4 protein (p.Leu663Met). This variant is not present in population databases (gnomAD no frequency). 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: 1007466). 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 expected to disrupt HCN4 protein function. 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. |
Ai |
RCV002224051 | SCV002502599 | uncertain significance | not provided | 2021-10-29 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV002486182 | SCV002785495 | uncertain significance | Sick sinus syndrome 2, autosomal dominant; Brugada syndrome 8; Epilepsy, idiopathic generalized, susceptibility to, 18 | 2021-09-13 | criteria provided, single submitter | clinical testing |