ClinVar Miner

Submissions for variant NM_005477.3(HCN4):c.3131G>A (p.Arg1044Gln) (rs750637152)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000180279 SCV000232681 uncertain significance not provided 2014-09-01 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000180279 SCV001149524 uncertain significance not provided 2018-07-01 criteria provided, single submitter clinical testing
Invitae RCV001210700 SCV001382199 uncertain significance Brugada syndrome 8 2019-06-29 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 1044 of the HCN4 protein (p.Arg1044Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. While this variant is present in population databases (rs750637152), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been observed in an individual who suffered an unexpected death (PMID: 30578647). ClinVar contains an entry for this variant (Variation ID: 198825). This variant has been reported to not to substantially affect HCN4 protein function (PMID: 30578647). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.

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.