Brugada syndrome and cardiac sodium channel disease
Gene: GPD1L
Brugada syndrome 2 (OMIM 611777)Created: 25 Mar 2019, 4:30 p.m.
Variant described in the London paper is recorded 36x on GnomAD. Also several asymptomatic patients have the variant. Variant described in the Huang paper describes nonsense variant assoc with SID that segregated in the family but 36 x on GnomAD. Other variants listed on OMIM as pathogenic at very high frequency on gnomAD. Evidence is not strong for monogenic cause. PMID:17967977. PMID:29077258. PMID:17967976Created: 25 Mar 2019, 4:27 p.m.
Mode of inheritance
Unknown
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/10149Created: 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. 13 variants listed on HGMD (accessed 29/01/2019). ClinGen Knowledge Base: disputed association with Brugada syndrome (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 2 (611777)
Publications
Variants in this GENE are reported as part of current diagnostic practice
Comment when marking as ready: On Manchester diagnostic panel
Multiple variants in unrelated individuals in OMIMCreated: 11 Feb 2016, 11:16 a.m.
PMID 17967977 - Identified variant through linkage and candidate gene approach. A280V detected in 16 phenotypically affected members of the family and in a further 27 phenotypically uncertain members. Functional studies suggest altered trafficking of SCN5A. Is in 25 of 126354 European alleles on gnomAD. PMID 17967976 - following detection of variant in PMID 17967977 this group screened SCD cases. E83K id in 3month old SCD which is in 37 of 128998 European alleles on GnomAD. PMID 17967976 - R273C in 1 month olf SIDS case which is in 12 of 111718 Europeans alleles in gnomAD. In conclusion - most variants identified to date are more frequent on gnomAD than the prevelance of Brugada syndrome which made it unlikely they are mendelian cause of disease.Created: 25 Jan 2019, 1:15 p.m.
Variants in this GENE are reported as part of current diagnostic practice
Phenotypes for gene: GPD1L were changed from Brugada syndrome 2 (611777) to Brugada syndrome 2, OMIM:611777
Phenotypes for gene: GPD1L were changed from Brugada syndrome 2 (611777); Brugada syndrome 2 to Brugada syndrome 2 (611777)
Gene: gpd1l has been classified as Red List (Low Evidence).
Source South West GLH was added to GPD1L. Mode of inheritance for gene GPD1L was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to Unknown
Source London South GLH was added to GPD1L.
Source North West GLH was added to GPD1L. Added phenotypes Brugada syndrome 2 (611777) for gene: GPD1L Publications for gene GPD1L were changed from to 27761167; 19666841 Rating Changed from Green List (high evidence) to Green List (high evidence)
This gene has been classified as Green List (High Evidence).
Model of inheritance for gene GPD1L was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
GPD1L was added to Brugada syndromepanel. Sources: UKGTN,Radboud University Medical Center, Nijmegen,Illumina TruGenome Clinical Sequencing Services,Emory Genetics Laboratory,Expert list
Model of inheritance for gene GPD1L was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
GPD1L was added to Brugada syndromepanel. Sources: UKGTN,Radboud University Medical Center, Nijmegen,Illumina TruGenome Clinical Sequencing Services,Emory Genetics Laboratory,Expert list
Model of inheritance for gene GPD1L was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
GPD1L was added to Brugada syndromepanel. Sources: UKGTN,Radboud University Medical Center, Nijmegen,Illumina TruGenome Clinical Sequencing Services,Emory Genetics Laboratory,Expert list
Model of inheritance for gene GPD1L was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
GPD1L was added to Brugada syndromepanel. Sources: UKGTN,Radboud University Medical Center, Nijmegen,Illumina TruGenome Clinical Sequencing Services,Emory Genetics Laboratory,Expert list
GPD1L was added to Brugada syndromepanel. Sources: UKGTN,Radboud University Medical Center, Nijmegen,Illumina TruGenome Clinical Sequencing Services,Emory Genetics Laboratory,Expert list