Brugada syndrome

Gene: HCN4

Red List (low evidence)

HCN4 (hyperpolarization activated cyclic nucleotide gated potassium channel 4)
EnsemblGeneIds (GRCh38): ENSG00000138622
EnsemblGeneIds (GRCh37): ENSG00000138622
OMIM: 605206, Gene2Phenotype
HCN4 is in 5 panels

6 reviews

Ivone Leong (Genomics England Curator)

Comment 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

Rebecca Whittington (South West GLH)

Green List (high evidence)

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_0c665867a80ab79d2af032616efe9099
Created: 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

Ellen McDonagh (Genomics England Curator)

Red List (low evidence)

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/10150
Created: 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

James Eden (Manchester)

Red List (low evidence)

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

Caroline Wright (Genomics England Curator)

Comment when marking as ready: On Manchester diagnostic panel
Created: 11 Feb 2016, 11:16 a.m.

Oxford Medical Genetics Laboratory (OUH NHS Foundation Trust)

Red List (low evidence)

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

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Red
  • South West GLH
  • London South GLH
  • North West GLH
  • Expert list
  • Emory Genetics Laboratory
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Brugada syndrome 8, OMIM:613123
OMIM
605206
Clinvar variants
Variants in HCN4
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

2 Mar 2021, Gel status: 1

Set Phenotypes

Ivone Leong (Genomics England Curator)

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

27 Feb 2019, Gel status: 1

Entity classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

Gene: hcn4 has been classified as Red List (Low Evidence).

21 Feb 2019, Gel status: 4

Added New Source, Set mode of inheritance

Ellen McDonagh (Genomics England Curator)

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

20 Feb 2019, Gel status: 4

Added New Source

Ellen McDonagh (Genomics England Curator)

Source London South GLH was added to HCN4.

14 Feb 2019, Gel status: 3

Added New Source, Set Phenotypes, Set publications, Status Update

Ellen McDonagh (Genomics England Curator)

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)

11 Feb 2016, Gel status: 4

Set Mode of Inheritance

Caroline Wright (Genomics England Curator)

Mode of inheritance for HCN4 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

11 Feb 2016, Gel status: 4

Gene classified by Genomics England curator

Caroline Wright (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

13 Jul 2015, Gel status: 3

Added New Source

Ellen McDonagh (Genomics England Curator)

HCN4 was added to Brugada syndromepanel. Sources: UKGTN,Radboud University Medical Center, Nijmegen,Emory Genetics Laboratory,Expert list

13 Jul 2015, Gel status: 3

Added New Source

Ellen McDonagh (Genomics England Curator)

HCN4 was added to Brugada syndromepanel. Sources: UKGTN,Radboud University Medical Center, Nijmegen,Emory Genetics Laboratory,Expert list

13 Jul 2015, Gel status: 2

Added New Source

Ellen McDonagh (Genomics England Curator)

HCN4 was added to Brugada syndromepanel. Sources: UKGTN,Radboud University Medical Center, Nijmegen,Emory Genetics Laboratory,Expert list

13 Jul 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

HCN4 was added to Brugada syndromepanel. Sources: UKGTN,Radboud University Medical Center, Nijmegen,Emory Genetics Laboratory,Expert list