Brugada syndrome and cardiac sodium channel disease

Gene: SCN5A

Green List (high evidence)

Submitted on behalf of the GMS Cardiology specialist group. The group has agreed that this gene should be Green on this panel.

Created: 18 Nov 2019, 2:25 p.m. | Last Modified: 18 Nov 2019, 2:25 p.m.

Panel Version: 1.45

MOI was changed from Biallelic back to Monoallelic after discussion with Helen Brittain (Genomics England Clinical Team).

Created: 27 Sep 2019, 1:47 p.m. | Last Modified: 27 Sep 2019, 1:47 p.m.

Panel Version: 1.45

Green List (high evidence)

Cardinal Gene for Brugada syndrome.

Created: 18 Sep 2019, 1:57 p.m. | Last Modified: 18 Sep 2019, 1:57 p.m.

Panel Version: 1.42

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

Green List (high evidence)

Atrial fibrillation, familial, 10 (OMIM 614022), Brugada syndrome 1 (OMIM 601144), Cardiomyopathy, dilated, 1E (OMIM 601154), Heart block, nonprogressive (OMIM 113900), Heart block, progressive, type IA (OMIM 113900), Long QT syndrome-3 (OMIM 603830), Sick sinus syndrome 1 (OMIM 608567), Ventricular fibrillation, familial, 1 (OMIM 603829-AR), {Sudden infant death syndrome, susceptibility to} (OMIM 272120-AR).

Created: 25 Mar 2019, 4:30 p.m.

Lots of literature evidence including prevalence of variants in affected individuals. PMID:20129283. PMID:23805106. PMID:24573164. PMID:22739120

Created: 25 Mar 2019, 4:27 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

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

Green List (high evidence)

Gene currently tested on Manchester cardiac gene panel. 914 variants listed on HGMD (accessed 29/01/2019). ClinGen Knowledge Base: definitive association with Brugada syndrome, association with long QT syndrome 3 (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 1

Publications

• 27761167
• 20031634

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

Green List (high evidence)

This gene was given a validity classification of Definitive by the ClinGen validity curation group and is reflected by providing a Green 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/10165

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.

Comment on publications: Promoter variant reported in PMID: 28391114 in a 16-year-old female who died during sleep.

Created: 14 Aug 2017, 1:47 p.m.

Mode of inheritance
Definitive

Phenotypes
Brugada syndrome; MONDO_0015263

Comment when marking as ready: On Manchester diagnostic panel

Created: 11 Feb 2016, 11:24 a.m.

Green List (high evidence)

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