ClinVar Miner

Submissions for variant NM_005477.3(HCN4):c.1915G>A (p.Val639Met) (rs563194186)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000179452 SCV000231703 uncertain significance not provided 2014-11-30 criteria provided, single submitter clinical testing
Invitae RCV001346820 SCV001541052 uncertain significance Brugada syndrome 8 2020-01-13 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 639 of the HCN4 protein (p.Val639Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. This variant is present in population databases (rs563194186, ExAC 0.04%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with HCN4-related conditions. ClinVar contains an entry for this variant (Variation ID: 198183). 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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