Table 1 Genetic details of RYR1-affected individuals

1/1

c.212C > A

p.Ser71Tyr

No

E 3

NTD-A

Pathogenic

[54, 55]

c.6847A > C

p.Asn2283His

E 42

BSol

Pathogenic

[54]

2/2

c.467G > A

p.Arg156Lys

No

E 6

NTD-A

Pathogenic

[55, 56]

3/3

c.487C > T

p.Arg163Cys

AD

E 6

NTD-A

Pathogenic

[57, 58]

4/3

c.487C > T

p.Arg163Cys

AD

E 6

NTD-A

Pathogenic

[57, 58]

5/3

c.487C > T

p.Arg163Cys

AD

E 6

NTD-A

Pathogenic

[57, 58]

6/4

c.487C > T

p.Arg163Cys

AD

E 6

NTD-A

Pathogenic

[57, 58]

7/5

c.1021G > A

p.Gly341Arg

AR

E 11

NTD-B

Pathogenic

[59, 60]

c.1021G > A

p.Gly341Arg

E 11

NTD-B

Pathogenic

[59, 60]

8/6

c.1209C > G

p.Ile403Met

No

E 12

NTD-B

Pathogenic

[61]

9/7

c.1250 T > C

p.Leu417Pro

No

E 13

NTD-C

Likely pathogenic

[62]

10/8

c.1840C > T

p.Arg614Cys

AD

E 17

NTD-C

Pathogenic

[63, 64]

11/9

c.3301G > A

p.Val1101Met

No

E 25

SPRY2/SPRY3

Likely pathogenic

[65]

c.14473C > T

p.Arg4825Cys

E 100

Pore

Pathogenic

[66]

12/10

c.4711A > G

p.Ile1571Val

No

E 33

SPRY2/SPRY3

Likely benign

[62, 67]

c.7373G > A

p.Arg2458His

E 46

BSol

Pathogenic

[68]

c.10097G > A

p.Arg3366His

E 67

BSol

Likely pathogenic

[67]

c.10259 + 7G > A

p.( =)

I 67

BSol

Benign

dbSNP: rs143752962

c.11798A > G

p.Tyr3933Cys

E 86

CSol

Pathogenic

[67, 69]

13/11

c.4711A > G

p.Ile1571Val

No

E 33

SPRY2/SPRY3

Likely benign

[62, 67]

c.10097G > A

p.Arg3366His

E 67

BSol

Likely pathogenic

[67]

c.11708G > A

p.Arg3903Gln

E 85

CSol

Pathogenic

[55]

c.11798A > G

p.Tyr3933Cys

E 85

CSol

Pathogenic

[67, 69]

14/12

c.4816C > T

p.Arg1606Cys

No

E 33

SPRY2/SPRY3

Pathogenic

[70]

15/13

c.5510A > C

p.Gln1837Pro

AD

E 34

JSol

Pathogenic

This paper

16/14

c.6488G > A

p.Arg2163His

No

E 39

BSol

Pathogenic

[57]

17/15

c.6502G > A

p.Val2168Met

AR

E 39

BSol

Pathogenic

[60]

c.7372C > T

p.Arg2458Cys

E 46

BSol

Pathogenic

[68]

18/16

c.7025A > G

p.Asn2342Ser

No

E 43

BSol

Pathogenic

[71]

c.14659C > T

p.His4887Tyr

E 102

Pore

Pathogenic

[72]

19/17

c.7048G > A

p.Ala2350Thr

AD

E 44

BSol

Pathogenic

[73]

20/17

c.7048G > A

p.Ala2350Thr

AD

E 44

BSol

Pathogenic

[73]

21/18

c.7085A > G

p.Glu2362Gly

AD

E 44

BSol

Pathogenic

[55]

c.13513G > C

p.Asp4505His

E 92

pVSD

Pathogenic

[74, 75]

22/19

c.7304G > A

p.Arg2435His

AD

E 45

BSol

Pathogenic

[60]

23/20

c.7523G > A

p.Arg2508His

No

E 47

BSol

Pathogenic

[20, 55]

24/21

c.9293G > T

p.Ser3098Ile

No

E 63

BSol

Pathogenic

This paper

c.14645C > T

p.Thr4882Met

E 101

Pore

Pathogenic

[76]

25/22

c.10097G > A

p.Arg3366His

AD

E 67

BSol

Likely pathogenic

[67]

c.11798A > G

p.Tyr3933Cys

E 86

CSol

Pathogenic

[67, 69]

26/23

c.11708G > A

p.Arg3903Gln

No

E 85

CSol

Pathogenic

[55]

27/24

c.11708G > A

p.Arg3903Gln

AR

E 85

CSol

Pathogenic

[55]

c.11708G > A

p.Arg3903Gln

E 85

CSol

Pathogenic

[55]

28/24

c.11708G > A

p.Arg3903Gln

AR

E 85

CSol

Pathogenic

[55]

c.11708G > A

p.Arg3903Gln

E 85

CSol

Pathogenic

[55]

29/25

c.13724A > C

p.Asn4575Thr

No

E 94

pVSD

Pathogenic

[77]

30/26

c.13910C > T

p.Thr4637Ile

No

E 95

pVSD

Pathogenic

[78]

31/27

c.14209C > T

p.Arg4737Trp

AD

E 98

pVSD

Pathogenic

[79, 80]

32/27

c.14209C > T

p.Arg4737Trp

AD

E 98

pVSD

Pathogenic

[79, 80]

33/28

c.14582G > A

p.Arg4861His

No

E 101

Pore

Pathogenic

[66, 78]

34/29

c.14680G > C

p.Ala4894Pro

AD

E 102

Pore

Pathogenic

[81]

35/29

c.14680G > C

p.Ala4894Pro

AD

E 102

Pore

Pathogenic

[81]

36/29

c.14680G > C

p.Ala4894Pro

AD

E 102

Pore

Pathogenic

[81]

37/29

c.14680G > C

p.Ala4894Pro

AD

E 102

Pore

Pathogenic

[81]

38/30

c.14690G > A

p.Gly4897Asp

No

E 102

Pore

Pathogenic

[82, 83]

39/31

c.14693 T > C

p.Ile4898Thr

AD

E 102

Pore

Pathogenic

[83,84,85]

40/31

c.14693 T > C

p.Ile4898Thr

AD

E 102

Pore

Pathogenic

[83,84,85]

41/32

c.14693 T > C

p.Ile4898Thr

AD

E 102

Pore

Pathogenic

[83,84,85]

42/33

c.14693 T > C

p.Ile4898Thr

No

E 102

Pore

Pathogenic

[83,84,85]

43/34

c.14695G > A

p.Gly4899Arg

AD

E 102

Pore

Pathogenic

[85, 86]

44/35

c.14818G > A

p.Ala4940Thr

AD

E 103

Pore

Pathogenic

[78]

45/36

c.14928C > G

p.Phe4976Leu

AR

E 104

CTD

Pathogenic

[87]

c.14928C > G

p.Phe4976Leu

E 104

CTD

Pathogenic

[87]

46/36

c.14928C > G

p.Phe4976Leu

AR

E 104

CTD

Pathogenic

[87]

c.14928C > G

p.Phe4976Leu

E 104

CTD

Pathogenic

[87]

47/37

c.472_474delGAA

p.Glu158del

No

E 6

NTD-A

Pathogenic

This paper

48/38

c.1690 T > C

p.Tyr564His

No

E 16

NTD-C

Benign

[85]

c.2930C > T

p.Thr977Met

E 24

RY1&2

Pathogenic

dbSNP: rs375865052

49/39

c.3866G > A

p.Arg1289Gln

No

E 28

SPRY2/SPRY3

Pathogenic

This paper

50/40

c.3901C > T

p.Arg1301Cys

No

E 28

SPRY2/SPRY3

Pathogenic

dbSNP: rs745920741

c.5360C > T

p.Pro1787Leu

E 34

JSol

Benign

[56]

51/41

c.3935C > T

p.Pro1312Leu

No

E 28

SPRY2/SPRY3

Benign

This paper

52/42

c.4949 T > C

p.Leu1650Pro

No

E 34

SPRY2/SPRY3

Pathogenic

This paper

c.6352C > T

p.Arg2118Trp

E 39

JSol

Pathogenic

[88]

c.14918C > T

p.Pro4973Leu

E 104

CTD

Likely pathogenic

[79]

53/43

c.6178G > T

p.Gly2060Cys

No

E 38

JSol

Benign

[54, 56]

c.13691G > A

p.Arg4564Gln

E 94

pVSD

Pathogenic

[7]

54/44

c.6352C > T

p.Arg2118Trp

AR

E 39

JSol

Pathogenic

[88]

c.14918C > T

c.10347 + 1G > A

p.Pro4973Leu

IVS68 + 1G > A

E 104

I 68

CTD

–

Likely pathogenic

Pathogenic

[79]

[88]

55/45

c.6377G > A

p.Arg2126Gln

No

E 39

JSol

Pathogenic

[89]

c.11813G > A

p.Gly3938Asp

E 86

CSol

Pathogenic

[89]

c.15022G > C

p.Glu5008Gln

E 106

CTD

Pathogenic

This paper

56/46

c.6617C > T

p.Thr2206Met

No

E 40

BSol

Pathogenic

[60]

c.10537A > G

p.Thr3513Ala

E 71

BSol

Pathogenic

This paper

57/47

c.9145C > T

p.Leu3049Phe

No

E 61

BSol

Pathogenic

This paper

58/48

c.10516C > A

p.Gln3506Lys

No

E 71

BSol

Pathogenic

This paper

59/49

c.11609-2A > G

IVS83-2A > G

AD

I 83

–

Uncertain significance

This paper

60/49

c.11609-2A > G

IVS83-2A > G

AD

I 83

–

Uncertain significance

This paper

61/50

c.13952A > G

p.His4651Arg

AD

E 95

pVSD

Pathogenic

dbSNP: rs118192139

62/50

c.13952A > G

p.His4651Arg

AD

E 95

pVSD

Pathogenic

dbSNP: rs118192139

63/51

c.14815G > T

p.Asp4939Tyr

AD

E 103

Pore

Pathogenic

This paper

64/51

c.14815G > T

p.Asp4939Tyr

AD

E 103

Pore

Pathogenic

This paper

65/52

c.12063insAC

c.2709_2711delCCC

p.Asp4021GlufsX4

p.His903del

AR

E 88

E 22

CSol

RY1&2

Pathogenic

Pathogenic

This paper

This paper

66/53

c.7080insG

p.Pro2361AlafsX2

No

E 44

BSol

Likely pathogenic

This paper

67/54

c.14510delA

p.Gln4837ArgfsX3

AD

E 100

Pore

Pathogenic

[56]

68/54

c.14510delA

p.Gln4837ArgfsX3

AD

E 100

Pore

Pathogenic

[56]

69/55

c.4711A > G

p.Ile1571Val

No

E 33

SPRY2/SPRY3

Likely benign

[62, 67]

c.9407delT*

p.Leu3136Argfs

E 63

BSol

Pathogenic

This paper