ClinVar Miner

Submissions for variant NM_005477.3(HCN4):c.134G>T (p.Arg45Leu)

gnomAD frequency: 0.00001  dbSNP: rs1416460262
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000557330 SCV000648434 uncertain significance Brugada syndrome 8 2022-09-20 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 45 of the HCN4 protein (p.Arg45Leu). 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 variant has not been reported in the literature in individuals affected with HCN4-related conditions. ClinVar contains an entry for this variant (Variation ID: 470647). 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. 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.
Fulgent Genetics, Fulgent Genetics RCV002491073 SCV002782404 uncertain significance Sick sinus syndrome 2, autosomal dominant; Brugada syndrome 8; Epilepsy, idiopathic generalized, susceptibility to, 18 2021-07-29 criteria provided, single submitter clinical testing

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