Table 2.
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.