Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001359109 | SCV001554971 | uncertain significance | Brugada syndrome 8 | 2020-10-28 | 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals with HCN4-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with serine at codon 650 of the HCN4 protein (p.Thr650Ser). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and serine. |
| Ambry Genetics | RCV002413845 | SCV002724010 | uncertain significance | Cardiovascular phenotype | 2020-06-08 | criteria provided, single submitter | clinical testing | The p.T650S variant (also known as c.1949C>G), located in coding exon 6 of the HCN4 gene, results from a C to G substitution at nucleotide position 1949. The threonine at codon 650 is replaced by serine, an amino acid with similar properties. This amino acid position is 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. |