Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001300689 | SCV001489838 | uncertain significance | Brugada syndrome 8 | 2020-10-08 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with HCN4-related conditions. 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the HCN4 gene (p.Glu981*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 223 amino acid(s) of the HCN4 protein. |