ClinVar Miner

Submissions for variant NM_005477.3(HCN4):c.3064C>T (p.Arg1022Ter)

gnomAD frequency: 0.00001  dbSNP: rs762950777
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000559988 SCV000648457 uncertain significance Brugada syndrome 8 2023-07-28 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg1022*) in the HCN4 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 182 amino acid(s) of the HCN4 protein. 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: 470663). 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 RCV002223873 SCV002502181 uncertain significance not provided 2022-03-07 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002506357 SCV002814166 uncertain significance Sick sinus syndrome 2, autosomal dominant; Brugada syndrome 8; Epilepsy, idiopathic generalized, susceptibility to, 18 2022-04-25 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004538033 SCV004117251 uncertain significance HCN4-related disorder 2023-09-03 criteria provided, single submitter clinical testing The HCN4 c.3064C>T variant is predicted to result in premature protein termination (p.Arg1022*). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0056% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/15-73615370-G-A). Loss of function has not been conclusively established as a mechanism for HCN4-related disorders. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.