ClinVar Miner

Submissions for variant NM_005477.3(HCN4):c.2399G>A (p.Arg800His) (rs375180021)

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
GeneDx RCV000489092 SCV000576606 uncertain significance not provided 2017-04-25 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the HCN4 gene. The R800H variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). However, the R800H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is only conserved in mammals and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.
Center for Advanced Laboratory Medicine, UC San Diego Health,University of California San Diego RCV000852709 SCV000995423 likely benign Cardiomyopathy 2018-05-02 criteria provided, single submitter clinical testing
Invitae RCV001060460 SCV001225148 uncertain significance Brugada syndrome 8 2019-12-11 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 800 of the HCN4 protein (p.Arg800His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs375180021, ExAC 0.01%). This variant has not been reported in the literature in individuals with HCN4-related conditions. ClinVar contains an entry for this variant (Variation ID: 426219). 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.