Mutations in RYR1

# genomic protein exon classification criteria
1 c.38T>G p.(Leu13Arg) 1 Pathogenic PSb PMb PPa PPc
2 c.103T>C p.(Cys35Arg) 2 Pathogenic PSb PPb PPa PPc
3 c.130C>T p.(Arg44Cys) 2 Pathogenic PSb PPb PPc
4 c.487C>T p.(Arg163Cys) 6 Pathogenic PSb PMb PPa PPb PPc
5 c.488G>T p.(Arg163Leu) 6 Pathogenic PSb PMb PPb PPc
6 c.529C>T p.(Arg177Cys) 6 Likely Pathogenic PMb PPa PPb PPc
7 c.742G>A p.(Gly248Arg) 9 Pathogenic PSa PMb PPb PPc
8 c.742G>C p.(Gly248Arg) 9 Pathogenic PSb PPa PPb PPc
9 c.1021G>A p.(Gly341Arg) 11 Pathogenic PSb PMb PPa PPb PPc
10 c.1021G>C p.(Gly341Arg) 11 Pathogenic PSb PMb PPb PPc
11 c.1201C>T p.(Arg401Cys) 12 Pathogenic PSb PMb PPb PPc
12 c.1202G>A p.(Arg401His) 12 Pathogenic PSb PMb PPb PPc
13 c.1565A>C p.(Tyr522Ser) 14 Pathogenic PSb PPb PPc
14 c.1565A>G p.(Tyr522Cys) 14 Likely Pathogenic PMb PPb PPc
15 c.1597C>T p.(Arg533Cys) 15 Pathogenic PSa PMb PPa PPb PPc
16 c.1615T>C p.(Phe539Leu) 15 Likely Pathogenic PMb PPb PPc
17 c.1654C>T p.(Arg552Trp) 15 Pathogenic PSb PMb PPc
18 c.1840C>T p.(Arg614Cys) 17 Pathogenic PSa PMb PPa PPb PPc
19 c.1841G>T p.(Arg614Leu) 17 Pathogenic PSb PMb PPa PPb PPc
20 c.5183C>T p.(Ser1728Phe) 34 Likely Pathogenic PMb PPa PPc
21 c.6487C>T p.(Arg2163Cys) 39 Pathogenic PSb PPa PPb PPc
22 c.6488G>A p.(Arg2163His) 39 Pathogenic PSb PMb PPa PPb PPc
23 c.6488G>C p.(Arg2163Pro) 39 Likely pathogenic PMb PPa PPb PPc
24 c.6502G>A p.(Val2168Met) 39 Pathogenic PSb PMb PPa PPb PPc
25 c.6612C>G p.(His2204Gln) 40 Likely pathogenic PMb PPa PPc
26 c.6617C>G p.(Thr2206Arg) 40 Pathogenic PSb PMb PPa PPb PPc
27 c.6617C>T p.(Thr2206Met) 40 Pathogenic PSb PMb PPa PPb PPc
28 c.6628G>T p.(Val2210Phe) 40 Likely Pathogenic PMb PPb PPc
30 c.7007G>A p.(Arg2336His) 43 Pathogenic PSb PMb PPa PPb PPc
31 c.7042_7044del p.(Glu2348del) 44 Pathogenic PSb PMb PPc
32 c.7048G>A p.(Ala2350Thr) 44 Pathogenic PSa PMb PPa PPb PPc
33 c.7063C>T p.(Arg2355Trp) 44 Pathogenic PSb PMb PPa PPb PPc
34 c.7090T>G p.(Phe2364Val) 44 Likely pathogenic PMb PPb PPb
35 c.7124G>C p.(Gly2375Ala) 44 Pathogenic PSb PMb PPa PPb PPc
36 c.7282G>A p.(Ala2428Thr) 45 Pathogenic PSb PPb PPc
37 c.7291G>T p.(Asp2431Tyr) 45 Pathogenic PSb PMb PPa PPb PPc
38 c.7300G>A p.(Gly2434Arg) 45 Pathogenic PSb PMb PPa PPb PPc
39 c.7304G>A p.(Arg2435His) 45 Pathogenic PSb PMb PPa PPb PPc
40 c.7304G>T p.(Arg2435Leu) 45 Likely pathogenic PMb PPb PPc
41 c.7310C>T p.(Ala2437Val) 45 Likely pathogenic PMb PPb PPc
42 c.7354C>T p.(Arg2452Trp) 46 Pathogenic PSb PMb PPa PPc
43 c.7360C>T p.(Arg2454Cys) 46 Pathogenic PSb PPb PPc
44 c.7361G>A p.(Arg2454His) 46 Pathogenic PSb PMb PPa PPb PPc
45 c.7372C>T p.(Arg2458Cys) 46 Pathogenic PSb PMb PPb PPc
46 c.7373G>A p.(Arg2458His) 46 Pathogenic PSb PMb PPa PPb PPc
47 c.7522C>T p.(Arg2508Cys) 47 Pathogenic PSb PMb PPb PPc
48 c.7523G>A p.(Arg2508His) 47 Pathogenic PSb PMb PPb PPc
49 c.8026C>T p.(Arg2676Trp) 50 Likely pathogenic PMb PPa PPc
50 c.9310G>A p.(Glu3104Lys) 63 Pathogenic PSb PMb PPa PPb PPc
51 c.11315G>A p.(Arg3772Gln) 79 Likely pathogenic PMb PPa PPb PPc
52 c.11708G>A p.(Arg3903Gln) 85 Likely pathogenic PMb PPb PPc
53 c.11969G>T p.(Gly3990Val) 87 Pathogenic PSb PMb PPa PPc
54 c.12533G>T p.(Gly4178Val) 90 Likely pathogenic PMb PPb. PPc
55 c.12700G>C p.(Val4234Leu) 91 Likely pathogenic PMb PPa PPb PPc
56 c.12700G>T p.(Val4234Leu) 91 Likely pathogenic PMb PPb PPc
57 c.14209C>T p.(Arg4737Trp) 98 Likely pathogenic PMb PPb PPc
58 c.14210G>A p.(Arg4737Gln) 98 Likely pathogenic PMb PPb PPc
59 c.14471T>C p.(Leu4824Pro) 100 Likely pathogenic PMb PPb PPc
60 c.14477C>T p.(Thr4826Ile) 100 Pathogenic PSb PMb Ppa PPb PPc
61 c.14497C>T p.(His4833Tyr) 100 Pathogenic PSb PPa PPb PPc
62 c.14512C>G p.(Leu4838Val) 101 Pathogenic PSb PMb PPb PPc
63 c.14545G>A p.(Val4849Ile) 101 Pathogenic PSb PMb PPa PPc
64 c.14582G>A p.(Arg4861His) 101 Pathogenic PSb PPb PPc
65 c.14627A>G p.(Lys4876Arg) 101 Likely pathogenic PMb PPa PPb PPc
66 c.14918C>T p.(Pro4973Leu) 104 Likely pathogenic PMb PPa PPb PPc

Mutations in CACNA1S

There are currently two mutations in the dihydropyridine recepter (Gen: CACNA1S) which are accepted as diagnostic mutations by the EMHG.

  • p.Arg1086His c.3257G>A

  • p.Arg174Trp c.520C>T

References:

Weiss RG, O’Connell KM, Flucher BE, Allen PD, Grabner M, Dirksen RT.  Functional analysis of the R1086H malignant hyperthermia mutation in the DHPR reveals an unexpected influence of the III-IV loop on skeletal muscle EC coupling. Am J Physiol Cell Physiol 2004; 287: C1094-102

Eltit JM, Bannister RA, Moua O, Altamirano F, Hopkins PM, Pessah IN, Molinski TF, Lopez JR, Beam KG, Allen PD: Malignant hyperthermia susceptibility arising from altered resting coupling between the skeletal muscle L-type Ca2+ channel and the type 1 ryanodine receptor. Proc Natl Acad Sci U S A 2012; 109: 7923-8