Table 2.
RYR1 Variants of Uncertain Significance in Malignant Hyperthermia-Susceptible Subjects
|
RYR1 Variants Amino Acid Substitution |
Exon | Caffeine-Halothane Contracture Test (g) |
Inclusion criteria |
Citation | |
|---|---|---|---|---|---|
| Caffeine 2mM | Halothane 3% | ||||
| Leu13Arg | 1 | 0.34 | 2.55 | MH | 4, 5 |
| Gly40Ala | 2 | 0.83 | 2.7 | FH | Current study (16) |
| Leu487Pro | 14 | 2.4 | 3.6 | FH | Current study |
| Val518Ala (a) | 14 | 1.0 | 1.3 | MH | Current study |
| Arg975Trp | 24 | na | na | CCD | Current study |
| Arg1043Cys (d) | 24 | 3.3 | 5.7 | MH, FH | 5, 17 |
| Arg1043His | 24 | 0.95 | 1.8 | FH | Current study (5,17) |
| Arg2248His (b) | 41 | 0.3 | 2.3 | MH | Current study (7) |
| Arg2336His (d) | 43 | 3.3 | 5.7 | MH, FH | 5, 17 |
| Asn2342Ser | 43 | 0.2 | 1.5 | MH | 17 |
| del Glu2347 | 44 | 1.36 | 5.9 | FH | 18 |
| Asn2351His | 44 | 0.5 | 5.0 | MH | Current study |
| Val2354Met | 44 | 1.25 | 3.4 | MH | Current study |
| Arg2355Trp | 44 | 2.6 | 9.5 | MH | 17, 19, 20 |
| Arg2355Trp | 44 | 1.82 | 1.6 | MH | 17, 19, 20 |
| Arg2355Trp | 44 | 0.3 | 5.1 | MH | 17, 19, 20 |
| Ile2358Leu (b) | 44 | 0.3 | 2.3 | MH | Current study |
| Arg2435Leu | 45 | 1.9 | 1.1 | FH | 7, 17, 21–23 |
| Arg2508His | 47 | na | na | MH, CCD | 15, 24 |
| Arg3238Gly | 66 | 0 | 0 | CCD | Current study |
| Arg3283Gln* | 66 | na | na | MH Death | Current study |
| Arg3539His | 71 | 0.8 | 5.2 | MH | 25, 26 |
| Glu3583Gln (c) | 72 | 1.0 | 2.6 | MH, FH | 17 |
| Thr3711Arg | 76 | 0.85 | 7.5 | FH | Current study |
| Tyr3933Cys (a) | 86 | 1.0 | 1.3 | MH | 7, 27 |
| Trp3985Arg | 87 | 1.2 | 2.2 | MH | 28 |
| Asp3986Glu | 87 | 1.9 | 8.8 | MH | 17 |
| Asp3986Glu | 87 | 2.5 | 10.8 | MH | 17 |
| Gly4178Val | 90 | 1.77 | 6.95 | FH | Current study |
| Met4230Arg | 91 | 3.3** | 6.3** | MH, FH | Current study |
| Gln4837Glu | 100 | 0.5 | 9.9 | FH | Current study |
| Val4847Leu | 101 | na | na | MH | 6 |
| Val4849Ile | 101 | 1.9 | 9.8 | MH | 2, 3, 29 |
| Val4849Ile | 101 | 0.3 | 3.6 | FH | 2, 3, 29 |
| Val4849Ile | 101 | 0.9 | 5.0 | MH, FH | 2, 3, 29 |
| Val4849Ile (c) | 101 | 1.0 | 2.6 | MH, FH | 2, 3, 29 |
| Ala4906Gly | 102 | 0.4 | 2.1 | FH | Current study (30) |
| Asp4939Glu | 103 | 2.0 | 11.3 | MH, FH | 31 |
| Ala4940Thr | 103 | 0.84 | 8.42 | FH | 3, 32–34 |
| Pro4973Leu | 104 | 0.85 | 2.1 | 22, 35 | |
na = not done; MH indicates that a personal episode of malignant hyperthermia was reported; FH indicates that a family history of MH was reported; CCD = central core disease; del = deletion.
When no data were available regarding an anonymized subject the cell remains empty. The letters (a), (b), (c) and (d) indicate the variants were both observed in a single subject, (a), (b), (c) and (d) respectively. Therefore there are 36 subjects represented in the 40 rows of this Table. The number appearing in parentheses below "current study" refers to the citation in which a different amino acid variant was reported at the same location. This was the case in 4 subjects in Table 2.
One RYR1 variant and a novel variant in CACNA1S found in this subject.
Caffeine-halothane contracture test (CHCT) was from soleus muscle; the parent had positive CHCT results from deltoid muscle.
Further details that are available regarding these subjects are presented in the Web Supplement.