Brugada syndrome

Gene: TRPM4

Red List (low evidence)

TRPM4 (transient receptor potential cation channel subfamily M member 4)
EnsemblGeneIds (GRCh38): ENSG00000130529
EnsemblGeneIds (GRCh37): ENSG00000130529
OMIM: 606936, Gene2Phenotype
TRPM4 is in 4 panels

7 reviews

Ivone Leong (Genomics England Curator)

Comment on phenotypes: This gene is also associated with Progressive familial heart block, type IB 604559
Created: 2 Mar 2021, 12:02 p.m. | Last Modified: 2 Mar 2021, 12:02 p.m.
Panel Version: 2.27

Rebecca Whittington (South West GLH)

Green List (high evidence)

Progressive familial heart block, type IB (OMIM 604559)
Created: 25 Mar 2019, 4:30 p.m.
Literature evidence including prevalence of variants in affected individuals and functional evidence. However appears mainly assoc with heart block /PCCD. PMID:23382873. PMID:29568272. https://www.ncbi.nlm.nih.gov/pubmed/21887725?dopt=Abstract. https://www.ncbi.nlm.nih.gov/pubmed/26820365?dopt=Abstract
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, 10:01 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/10164
Created: 20 Feb 2019, 2:47 p.m.
Comments from Matthew Edwards Royal Brompton Hospital sent 16th Jan 2019 on behalf of the London South GLH for review by the GMS Cardiology Specialist Group: Liu paper (PMID: 23382873) variants: 8/14 variants listed in paper have AFs likely to be incompatible with prevalence of disease of others all are VUS via ACMG guidelines. Stallmeyer paper (PMID: 21887725) similar and all RBBB phenotype no Brugada. Possible inclusion for R328? Need for separate BrS panel if cardiac conducation disease panel available.
Created: 20 Feb 2019, 2:17 p.m.

Mode of inheritance
Disputed

Phenotypes
Brugada syndrome; MONDO_0015263

Publications

James Eden (Manchester)

Red List (low evidence)

Gene currently tested on Manchester cardiac gene panel. Only class 1-3 variants detected to date. 36 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
Progressive familial heart block, type IB (604559)

Publications

Variants in this GENE are reported as part of current diagnostic practice

Eleanor Williams (Genomics England Curator)

Comment on phenotypes: Added phenotype from OMIM
Created: 16 Jan 2019, 11:58 a.m.

Caroline Wright (Genomics England Curator)

Comment when marking as ready: On Manchester diagnostic panel; functional evidence in multiple unrelated individuals described in 2013 paper in association with BrS
Created: 11 Feb 2016, 12:29 p.m.
Comment on list classification: 2013 paper: Molecular genetics and functional anomalies in a series of 248 Brugada cases with 11 mutations in the TRPM4 channel.
Created: 11 Feb 2016, 12:27 p.m.

Oxford Medical Genetics Laboratory (OUH NHS Foundation Trust)

Red List (low evidence)

Evidence of variants in this gene leading to progressive familial heart block but not for BS.
Created: 25 Jan 2019, 1:15 p.m.

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Red
  • South West GLH
  • North West GLH
Phenotypes
  • Brugada syndrome, MONDO:0015263
OMIM
606936
Clinvar variants
Variants in TRPM4
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: TRPM4 were changed from Progressive familial heart block, type IB 604559; Progressive familial heart block, type IB (604559) to Brugada syndrome, MONDO:0015263

27 Feb 2019, Gel status: 1

Entity classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

Gene: trpm4 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 TRPM4. Mode of inheritance for gene TRPM4 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

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 TRPM4. Added phenotypes Progressive familial heart block, type IB (604559) for gene: TRPM4 Publications for gene TRPM4 were changed from http://www.ncbi.nlm.nih.gov/pubmed/23382873 to 23382873; 27761167 Rating Changed from Green List (high evidence) to Green List (high evidence)

16 Jan 2019, Gel status: 3

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: TRPM4 were changed from to Progressive familial heart block, type IB 604559

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).

11 Feb 2016, Gel status: 4

Set Mode of Inheritance

Caroline Wright (Genomics England Curator)

Mode of inheritance for TRPM4 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).

11 Feb 2016, Gel status: 0

Set publications

Caroline Wright (Genomics England Curator)

Publications for TRPM4 were set to http://www.ncbi.nlm.nih.gov/pubmed/23382873

6 Jan 2016, Gel status: 0

Added New Source

Oxford Medical Genetics Laboratory (OUH NHS Foundation Trust)

TRPM4 was added to Brugada syndromepanel. Sources: Oxford Medical Genetics Laboratory

6 Jan 2016, Gel status: 0

Created

Oxford Medical Genetics Laboratory (OUH NHS Foundation Trust)

TRPM4 was created by OxfordGenetics