Brugada syndrome and cardiac sodium channel disease

Gene: TRPM4

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

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

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

• 21887725
• 23382873

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

• 23382873
• 27761167

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

Comment on phenotypes: Added phenotype from OMIM

Created: 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 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.

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.