ClinVar Miner

Submissions for variant NM_005477.3(HCN4):c.23T>C (p.Met8Thr)

dbSNP: rs749801134
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001939916 SCV002179003 uncertain significance Brugada syndrome 8 2022-03-18 criteria provided, single submitter clinical testing The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 8 of the HCN4 protein (p.Met8Thr). This variant has not been reported in the literature in individuals affected 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. 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 not expected to disrupt HCN4 protein function.

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