Dilated and arrhythmogenic cardiomyopathy

Gene: RYR2

Green List (high evidence)

Submitted on behalf of the GMS Cardiology specialist group. This gene did not achieve a consensus Green rating; however, the group agreed that the existing evidence (published and in-house data) was sufficient to support inclusion in this panel.

Created: 9 Dec 2019, 1:19 p.m. | Last Modified: 9 Dec 2019, 1:19 p.m.

Panel Version: 0.61

I don't know

RYR2 is not currently tested in Manchester for DCM. RYR2 (whole gene) is associated with ARVD and CPVT on OMIM. Limited association of RYR2 variants with DCM. The RYR2 exon 3 deletion was reported in one article in 2 families with CPVT combined with additional features of dilated cardiomyopathy (https://www.ncbi.nlm.nih.gov/pubmed/17875969) This deletion is more commonly associated with LVNC cardiomyopathy in the literature (https://www.ncbi.nlm.nih.gov/pubmed/24394973, https://www.ncbi.nlm.nih.gov/pubmed/26018045)

Created: 27 Sep 2019, 11:37 a.m. | Last Modified: 27 Sep 2019, 11:37 a.m.

Panel Version: 0.46

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Arrhythmogenic right ventricular dysplasia 2 600996; Ventricular tachycardia, catecholaminergic polymorphic, 1 604772

Publications

• 17875969

Green List (high evidence)

On CGGL Royal Brompton DCM panel. Definitive CPVT gene, appropriate for DCM panel due to possible phenotypic overlap as some evidence for exon 3 deletion specifically associated with DCM.

Created: 19 Sep 2019, 10:14 p.m. | Last Modified: 8 Apr 2021, 11:42 p.m.

Panel Version: 1.13

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

I don't know

Submitted on behalf of the GMS Cardiology specialist group. Demoted from Green to Amber. The group has agreed that this gene should be Amber on this panel. Testing should involve dosage analysis only in this gene.

Created: 3 Dec 2019, 2:28 p.m. | Last Modified: 3 Dec 2019, 2:28 p.m.

Panel Version: 0.52

RYR2 is a green gene on the Arrhythmogenic cardiomyopathy (code: 134, version 1.25). It has been promoted from amber to green in this panel as the GMS Cardiology Specialist Group decided that all green genes that are present on the Arrhythmogenic cardiomyopathy panel should also be green on this panel because of the overlap in clinical presentation.

Created: 4 Sep 2019, 10:51 a.m. | Last Modified: 4 Sep 2019, 10:51 a.m.

Panel Version: 0.37

Red List (low evidence)

Arrhythmogenic right ventricular dysplasia 2 (600996); Ventricular tachycardia, catecholaminergic polymorphic, 1 (604772)

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

PubMED: 29567486 - core gene. Lots of entries on HGMDPro for CPVT as considered to be the main gene. Reported C5 RYR2 assoc with short QT. Multiple variants on HGMD however pathogenicity downgraded to VUS: Pubmed: 28404607. Insufficient evidence to include.

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

I don't know

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.

Green List (high evidence)

Discussed with NHS GMS cardiology specialist group 25.01.19. Only recurrent exon 3 deletion is reliably associated with ARVC.

Created: 4 Feb 2019, 7:27 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Arrhythmogenic right ventricular cardiomyopathy

Publications

• PMID:19926015
• 17875969

I don't know

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Mode of pathogenicity
Other

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

Green List (high evidence)

Comment when marking as ready: Lots of patient reported with ARVC/D and rare variants in RYR2

Created: 14 Feb 2016, 3:51 p.m.