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Table 2 Mutations of ryanodine receptor type 1

From: Functional and genetic characterization of clinical malignant hyperthermia crises: a multi-centre study

     In vitro contracture test        
       Contracture Threshold       
Exon Nucleotide Substitution No. of patients in this study 2 vol% halothane [mN] 2 mmoll-1caffeine [mN] Halothane [vol%] Caffeine [mmoll-1] Clinical grading scale Causative mutation? PolyPhen2 predictions Sift predictions Mutation Taster predictions Reference
2 c.130C>T p.R44C 1 12.0 10.8 0.5 1.0 78.0 No     Tammaro et al. 2003 [28]
3 c.178G>T p.D60Y 1 13.0 4.5 1.0 2.0 30.0 No + + + This study, V. Sorrentino
11 c.1021G>A p.G341R 3 14.3 ± 4.8 13.7
± 3.1
0.8 ± 0.2 0.8 ± 0.5 54.3 ± 4.9 Yes     Quane et al. 1994 [29]
11 c.1024G>A p.E342K 1 37.8 23.8 0.5 0.5 30.0 No + + + This study, K. Jurkat-Rott
11 c.1100G>A p.R367Q 1 10.0 4.1 0.5 1.5 15.0 No     Galli et al. 2006 [30]
12 c.1201C>T p.R401C 1 17.0 7.0 1.0 1.5 18.0 No     Davis et al. 2002 [31]
12 c.1202G>A p.R401H 1 21.0 12.0 1.0 1.5 55.0 No     Rüffert et al. 2002 [32]
15 c.1655G>A p.R552Q* 1 36.0 8.0 0.5 1.5 38.0 No + - + This study, V. Sorrentino
17 c.1840C>T p.R614C 25 13.7 ± 8.9 10.5
± 8.3
0.9 ± 0.5 1.3 ± 0.7 50.8 ± 22.3 Yes     Gillard et al. 1992 [33]
17 c.1841G>T p.R614L 2 16.6 ± 2.6 8.3 ± 2.3 0.5 ± 0.0 1.0 ± 0.5 30.5 ± 2.5 Yes     Quane et al. 1997 [34]
34 c.5011G>A p.A1671T 1 8.0 24.8 2.0 0.5 35.0 No + + - This study, K. Jurkat-Rott
38 c.6178G>T p.G2060C* 1 16.4 8.0 0.5 1.0 88.0 No     Robinson et al. 2006 [6]
39 c.6377G>A p.R2126Q 1 26.8 8.8 0.5 2.0 35.0 No     Kraeva et al. 2011 [7]
39 c.6387C>G p.D2129E 1 10.0 11.0 2.0 1.0 45.0 No     Rüffert et al. 2001 [35]
39 c.6488G>C p.R2163P 1 20.0 4.0 1.0 2.0 55.0 No     Robinson et al. 2006 [6]
39 c.6502G>A p.V2168M 6 22.5 ± 7.1 12.3 ± 5.0 0.5 ± 0.0 1.1 ± 0.3 58.8 ± 20.5 Yes     Manning et al. 1998 [36]
40 c.6599C>T p.A2200V 1 - 3.0 - 2.0 10.0 No     Sambuughin et al. 2005 [37]
40 c.6617C>T p.T2206M 9 20.5 ± 10.7 10.4 ± 4.9 0.9 ± 0.4 1.0 ± 0.4 50.4 ± 16.2 Yes     Manning et al. 1998 [36]
41 c.6710G>A p.C2237Y 1 6.0 6.0 0.5 1.0 38.0 No + + + This study, M. Snoeck
43 c.7007G>A p.R2336H 4 12.8 ± 4.5 11.7 ± 6.1 0.8 ± 0.3 1.1 ± 0.2 47.3 ± 4.4 No     Levano et al. 2009 [38]
43 c.7025A>G p.N2342S 1 3.0 0.0 2.0 4.0 30.0 No     Marchant et al. 2004 [39]
44 c.7034G>C p.S2345T 1 32.0 24.0 0.5 1.0 28.0 No (+) - + This study, V. Sorrentino
44 c.7048G>A p.A2350T 1 22.0 9.0 1.0 1.0 55.0 Yes     Sambuughin et al. 2001 [40]
44 c.7076G>A p.R2359Q 1 3.0 4.0 2.0 2.0 15.0 No (+) - + This study, H. Rüffert
44 c.7085A>G p.E2362G 1 16.0 8.0 0.5 1.0 43.0 No     Galli et al. 2006 [30]
44 c.7112A>G p.E2371G 1 16.0 10.0 1.0 1.5 91.0 No     Zullo et al. 2009 [26]
44 c.7124G>C p.G2375A 2 19.5 ± 0.5 20.5 ± 1.5 0.5 ± 0.0 0.8 ± 0.3 59.5 ± 11.5 Yes     Rüffert et al. 2002 [41]
45 c.7300G>A p.G2434R 5 24.3 ± 14.4 12.2 ± 8.2 0.7 ± 0.2 1.1 ± 0.6 57.4 ± 19.9 Yes     Sambuugghin et al. 2001 [42]
46 c.7354C>T p.R2452W 1 8.0 20.0 1.0 1.5 48.0 No     Chamley et al. 2000 [43]
46 c.7358T>C p.I2453T 1 7.0 7.0 1.0 1.5 63.0 No     Rüffert et al. 2002 [41]
46 c.7360C>T p.R2454C 1 9.2 6.0 0.5 1.0 28.0 Yes     Brandt et al. 1999 [44]
46 c.7361G>A p.R2454H 3 15.3 ± 5.7 13.0 ± 6.5 0.8 ± 0.2 1.0 ± 0.4 48.0 ± 12.2 Yes     Barone et al. 1999 [45]
46 c.7372C>T p.R2458C 2 7.3 ± 1.3 2.0 ± 1.0 1.0 ± 0.0 2.0 ± 0.0 41.5 ± 31.5 Yes     Manning et al. 1998 [46]
71 c.10616G˃A p.R3539H 1 7.0 8.0 2.0 1.5 38.0 No     Dekomien et al. 2005 [47]
85 c.11708G>A p.R3903Q 2 4.8 ± 0.2 2.5 ± 0.5 2.0 ± 0.0 2.0 ± 0.0 25.0 ± 5.0 No     Galli et al. 2006 [30]
85 c.11723A>T p.N3908I 1 8.0 4.8 1.0 1.5 20.0 No + + + This study, K. Jurkat-Rott
90 c.12398A>G p.E4133G 1 2.0 2.5 2.0 2.0 10.0 No + + + This study, V. Sorrentino
90 c.12413T>C p.I4138T 1 11.0 15.0 1.0 1.0 25.0 No     Robinson et al. 2006 [6]
90 c.12532G>A p.G4178S 1 32.0 8.0 0.5 1.5 38.0 No + + + This study, V. Sorrentino
95 c.13990T>C p.C4664R 1 20.0 4.0 1.5 1.5 50.0 No     Zullo et al. 2009 [26]
98 c.14204G>A p.R4735Q 1 7.0 5.0 1.0 1.5 50.0 No + - + This study, H. Rüffert
101 c.14545G>A p.V4849I 3 3.8 ± 3.1 3.3 ± 0.8 1.5 ± 0.5 2.0 ± 0.0 36.3 ± 8.5 No     Jungbluth et al. 2002 [48]
101 c.14627A>G p.K4876R 1 14.0 14.0 0.5 0.5 48.0 No     Monnier et al. 2005 [49]
103 c.14833C>T p.R4945X 1 9.9 23.3 0.5 0.5 15.0 No na na + This study, K. Jurkat-Rott
106 c.15059G>C p.W5020S 1 1.0 2.0 - 2.0 43.0 No + + + This study, V. Sorrentino
  1. Overview of all ryanodine receptor type 1 (RyR1) mutations that have been detected in this study. If more than one patient carried the same mutation results of in vitro contracture tests (IVCT) and clinical grading scales are shown as mean ± standard deviation. Patients with double RyR1 mutations are listed separately. Novel variations (n = 13) are highlighted (bold). Polymorphisms (n = 2) are marked with asterisks (*). Polyphen2: + = probably damaging, (+) = possibly damaging, - = benign, na = not applicable to truncations; Sift: + = deleterious, - = tolerated, na = not applicable to truncations; Mutation taster: + = disease-causing; - = polymorphism.