ClinVar Miner

Submissions for variant NM_005477.3(HCN4):c.1987C>A (p.Leu663Met)

gnomAD frequency: 0.00001  dbSNP: rs1265876338
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001304652 SCV001493945 uncertain significance Brugada syndrome 8 2022-08-03 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 663 of the HCN4 protein (p.Leu663Met). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with HCN4-related conditions. ClinVar contains an entry for this variant (Variation ID: 1007466). 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.
AiLife Diagnostics, AiLife Diagnostics RCV002224051 SCV002502599 uncertain significance not provided 2021-10-29 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002486182 SCV002785495 uncertain significance Sick sinus syndrome 2, autosomal dominant; Brugada syndrome 8; Epilepsy, idiopathic generalized, susceptibility to, 18 2021-09-13 criteria provided, single submitter clinical testing

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