ClinVar Miner

Submissions for variant NM_005477.3(HCN4):c.433C>G (p.Pro145Ala)

gnomAD frequency: 0.00001  dbSNP: rs886043525
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) RCV000346829 SCV000340535 uncertain significance not provided 2016-03-31 criteria provided, single submitter clinical testing
Invitae RCV000647230 SCV000769019 uncertain significance Brugada syndrome 8 2023-12-02 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 145 of the HCN4 protein (p.Pro145Ala). This variant is not present in population databases (gnomAD no frequency). 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: 286934). 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 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.
Ambry Genetics RCV003278740 SCV004003461 uncertain significance Cardiovascular phenotype 2023-05-18 criteria provided, single submitter clinical testing The p.P145A variant (also known as c.433C>G), located in coding exon 1 of the HCN4 gene, results from a C to G substitution at nucleotide position 433. The proline at codon 145 is replaced by alanine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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.