Arrhythmogenic right ventricular cardiomyopathy

Gene: RYR2

Red List (low evidence)

Gene-disease association assessed as REFUTED by ClinGen: 57 papers reviewed in the process. Some of the original variants were relatively often present in reference alleles from the gnomAD database, clear ARVD diagnosis was not provided, segregation information was not informative and/or CPVT was also present in the family. In a recent review it was also recognized that the observed phenotype in the original three publications that reported RYR2 variants in ARVD for the first time should be catecholamine-induced ventricular tachycardia rather than ARVD, and this gene is no longer considered as ARVD causing (29543670).

Created: 3 Aug 2020, 7:02 a.m. | Last Modified: 3 Aug 2020, 7:02 a.m.

Panel Version: 2.6

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Arrhythmogenic right ventricular dysplasia 2, MIM# 600996

Publications

• 11159936
• 25041964
• 29543670

I don't know

The rating of this gene has been updated following NHS Genomic Medicine Service approval.

Created: 3 Mar 2022, 10:46 a.m. | Last Modified: 3 Mar 2022, 10:46 a.m.

Panel Version: 2.15

Have tagged with "for-review" for the next major review of the panel.

Created: 4 Aug 2020, 3:31 p.m. | Last Modified: 4 Aug 2020, 3:31 p.m.

Panel Version: 2.7

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

Created: 2 Dec 2019, 1:28 p.m. | Last Modified: 2 Dec 2019, 1:28 p.m.

Panel Version: 1.45

I don't know

RYR2 (whole gene) is associated with ARVD and CPVT on OMIM. Not currently tested in Manchester for ARVC. Some literature associating RYR2 variants with ARVC.

Created: 27 Sep 2019, 9:19 a.m. | Last Modified: 27 Sep 2019, 9:19 a.m.

Panel Version: 1.36

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

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

Publications

• 25041964
• 27761164

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.