Table 2.

Paralogue annotation of novel variants identified in RYR2

RYR2 variant
CDS	Protein	Region	Cases (n=155)	Exon	Paralogue	Paralogue variant	Paralogue disease	Consensus
c.527G>A	p.R176Q	N-terminal hotspot	1	8	RYR1	R163L	Malignant hyperthermia	9
					RYR1	R163C	Central core disease	9
c.994C>T	p.R332W	N-terminal hotspot	1	12	RYR1	R316L	Malignant hyperthermia	8
c.1069G>A	p.G357S	N-terminal hotspot	1	13	RYR1	G341R	Malignant hyperthermia	9
					RYR1	G341R	Malignant hyperthermia	9
c.1646C>T	p.A549V	Outside hotspots	1	17	RYR1	A537T	Congenital myopathy	9
c.6504C>G	p.H2168Q	Outside hotspots	2	42	RYR1	H2204Q	Multiminicore disease	9
c.7258A>T	p.R2420W	Central hotspot	1	48	RYR1	R2454C	Malignant hyperthermia	9
					RYR1	R2454H	Malignant hyperthermia	9
c.11989A>G	p.K3997E	Channel hotspot	1	90	RYR1	R4041W	Malignant hyperthermia	9
c.14369G>A	p.R4790Q	Channel hotspot	1	100	RYR1	R4861C	Central core disease	9
					RYR1	R4861H	Central core disease	9
c.14414A>G	p.K4805R	Channel hotspot	1	100	RYR1	K4876R	Malignant hyperthermia	9
c.14465G>A	p.R4822H	Channel hotspot	1	101	RYR1	R4893W	Central core disease	9
					RYR1	R4893Q	Central core disease	9
					RYR1	R4893P	Central core disease	9

Ten out of 31 novel missense variants identified in 155 unrelated CPVT patients¹⁰ were annotated. This provides strong evidence of pathogenicity for these variants. In addition, five of the 29 RYR2 missense variants previously reported to be pathogenic were annotated (see supplementary table S1, available online only).

RYR2 coordinates given with respect to transcripts NM_001035/NP_001026 (Refseq), ENST00000366574/ENSP00000355533 (Ensembl), LRG_402t1/LRG_402p1 (Locus Reference Genomic).

CDS, coding DNA sequence; CPVT, catecholaminergic polymorphic ventricular tachycardia.