Brugada syndrome and cardiac sodium channel disease
Gene: HCN4Comment on phenotypes: This gene is also associated with Sick sinus syndrome 2 (163800)Created: 2 Mar 2021, 11:48 a.m. | Last Modified: 2 Mar 2021, 11:48 a.m.
Panel Version: 2.14
Brugada syndrome 8 (OMIM 613123), Sick sinus syndrome 2 (OMIM 163800)Created: 25 Mar 2019, 4:30 p.m.
Milano (2014) paper (25145517) showed segregation / ?functional effect. Macri paper (24607718) showed functional effect. PMID: 27553229. https://ac.els-cdn.com/S0735109716015862/1-s2.0-S0735109716015862-main.pdf?_tid=89c56f79-58d9-413a-a162-598c96f24a0b&acdnat=1546869351_0c665867a80ab79d2af032616efe9099Created: 25 Mar 2019, 4:27 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Variants in this GENE are reported as part of current diagnostic practice
Comment on list classification: Due to new expert reviews and disputed evidence for this gene-disease causation, this gene has been demoted from Green to Red.Created: 27 Feb 2019, 9:58 a.m.
This gene was given a validity classification of Disputed by the ClinGen validity curation group and is reflected by providing a Red review here.The gene-disease summary was downloaded on 20th Feb 2019.For the full report and publications see the ClinGen Gene Validity Curation for each gene here: https://search.clinicalgenome.org/kb/gene-validity/10150Created: 20 Feb 2019, 2:47 p.m.
This gene was part of an initial gene list collated by Matthew Edwards Royal Brompton Hospital sent 16th Jan 2019 on behalf of the London South GLH for review by the GMS Cardiology Specialist Group. Only gene symbol from the Royal Brompton gene panel was provided - suggested initial gene rating and evidence for inclusion not provided with the list.Created: 20 Feb 2019, 2:17 p.m.
Mode of inheritance
Disputed
Phenotypes
Brugada syndrome 1; MONDO_0011001
Gene currently tested on Manchester cardiac gene panel. Only class 1-3 variants detected to date. 37 variants listed on HGMD (accessed 29/01/2019). ClinGen Knowledge Base: disputed association with Brugada syndrome 1 (accessed 29/01/2019).Created: 14 Feb 2019, 1:38 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Brugada syndrome 8 (613123); Sick sinus syndrome 2 (163800)
Publications
Variants in this GENE are reported as part of current diagnostic practice
Comment when marking as ready: On Manchester diagnostic panelCreated: 11 Feb 2016, 11:16 a.m.
Mouse studies suggest homozygous knockout is embryonic lethal. Heterozygous littermates were phenotypically indistinguishable from WT. Most variants reported are in sick sinus syndrome or with sinus bradycardia. 2 variants id in this gene in isolated cases of brugada syndrome (1 was asymptomatic) - minimal evidence suggesting pathogenicity for BS. Suggest Red gene for BS - Green gene for sick sinus syndrome - Green gene on molecular autopsy panel.Created: 25 Jan 2019, 1:15 p.m.
Variants in this GENE are reported as part of current diagnostic practice
Phenotypes for gene: HCN4 were changed from Sick sinus syndrome 2 (163800); Brugada syndrome 8; Brugada syndrome 8 (613123) to Brugada syndrome 8, OMIM:613123
Gene: hcn4 has been classified as Red List (Low Evidence).
Source South West GLH was added to HCN4. Mode of inheritance for gene HCN4 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Source London South GLH was added to HCN4.
Source North West GLH was added to HCN4. Added phenotypes Sick sinus syndrome 2 (163800); Brugada syndrome 8 (613123) for gene: HCN4 Publications for gene HCN4 were changed from to 27761167 Rating Changed from Green List (high evidence) to Green List (high evidence)
Mode of inheritance for HCN4 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
This gene has been classified as Green List (High Evidence).
HCN4 was added to Brugada syndromepanel. Sources: UKGTN,Radboud University Medical Center, Nijmegen,Emory Genetics Laboratory,Expert list
HCN4 was added to Brugada syndromepanel. Sources: UKGTN,Radboud University Medical Center, Nijmegen,Emory Genetics Laboratory,Expert list
HCN4 was added to Brugada syndromepanel. Sources: UKGTN,Radboud University Medical Center, Nijmegen,Emory Genetics Laboratory,Expert list
HCN4 was added to Brugada syndromepanel. Sources: UKGTN,Radboud University Medical Center, Nijmegen,Emory Genetics Laboratory,Expert list