ClinVar Miner

Submissions for variant NM_005477.3(HCN4):c.1159C>T (p.Arg387Cys)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001294623 SCV001483507 uncertain significance Brugada syndrome 8 2020-07-22 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 387 of the HCN4 protein (p.Arg387Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with HCN4-related conditions. 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.

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