Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001351771 | SCV001546266 | uncertain significance | Brugada syndrome 8 | 2020-03-19 | 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. This variant has not been reported in the literature in individuals with HCN4-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This sequence change replaces alanine with threonine at codon 149 of the HCN4 protein (p.Ala149Thr). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and threonine. |
| Ambry Genetics | RCV002329345 | SCV002638836 | uncertain significance | Cardiovascular phenotype | 2020-03-17 | criteria provided, single submitter | clinical testing | The p.A149T variant (also known as c.445G>A), located in coding exon 1 of the HCN4 gene, results from a G to A substitution at nucleotide position 445. The alanine at codon 149 is replaced by threonine, an amino acid with 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. |