ClinVar Miner

Submissions for variant NM_005477.3(HCN4):c.2555C>T (p.Pro852Leu)

gnomAD frequency: 0.00002  dbSNP: rs779241036
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
Eurofins Ntd Llc (ga) RCV000326913 SCV000343606 uncertain significance not provided 2016-07-29 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000702797 SCV000831667 uncertain significance Brugada syndrome 8 2024-09-23 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 852 of the HCN4 protein (p.Pro852Leu). This variant is present in population databases (rs779241036, gnomAD 0.003%). This missense change has been observed in individual(s) with dilated cardiomyopathy and atrioventricular block (PMID: 28254188). ClinVar contains an entry for this variant (Variation ID: 289273). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt HCN4 protein function with a negative predictive value of 95%. 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 RCV002480042 SCV002780808 uncertain significance Sick sinus syndrome 2, autosomal dominant; Brugada syndrome 8; Epilepsy, idiopathic generalized, susceptibility to, 18 2021-10-19 criteria provided, single submitter clinical testing

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.