Brugada syndrome and cardiac sodium channel disease
Gene: TRPM4Comment on phenotypes: This gene is also associated with Progressive familial heart block, type IB 604559Created: 2 Mar 2021, 12:02 p.m. | Last Modified: 2 Mar 2021, 12:02 p.m.
Panel Version: 2.27
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=AbstractCreated: 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, 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/10164Created: 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
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
Comment on phenotypes: Added phenotype from OMIMCreated: 16 Jan 2019, 11:58 a.m.
Comment when marking as ready: On Manchester diagnostic panel; functional evidence in multiple unrelated individuals described in 2013 paper in association with BrSCreated: 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.
Evidence of variants in this gene leading to progressive familial heart block but not for BS.Created: 25 Jan 2019, 1:15 p.m.
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
Gene: trpm4 has been classified as Red List (Low Evidence).
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
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)
Phenotypes for gene: TRPM4 were changed from to Progressive familial heart block, type IB 604559
This gene has been classified as Green List (High Evidence).
Mode of inheritance for TRPM4 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
This gene has been classified as Green List (High Evidence).
Publications for TRPM4 were set to http://www.ncbi.nlm.nih.gov/pubmed/23382873
TRPM4 was added to Brugada syndromepanel. Sources: Oxford Medical Genetics Laboratory
TRPM4 was created by OxfordGenetics