Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000647244 | SCV000769033 | uncertain significance | Brugada syndrome 8 | 2017-10-26 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C65"). This variant has not been reported in the literature in individuals with HCN4-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces tryptophan with cysteine at codon 341 of the HCN4 protein (p.Trp341Cys). The tryptophan residue is highly conserved and there is a large physicochemical difference between tryptophan and cysteine. |