| | Max Magnitude | Chromosome position | Summary |
|---|
| i3002484 | | | |
| i3002773 | | | |
| i5000011 | | | |
| i5000015 | | | |
| i5000016 | | | |
| i5000017 | | | |
| i5000020 | | | |
| i5000022 | | | |
| i5000024 | | | |
| i5008290 | | | |
| i5900460 | | | |
| i6017603 | | | |
| i6017606 | | | |
| i6017636 | | | |
| i6017652 | | | |
| i6017660 | | | |
| i6017661 | | | |
| i6017662 | | | |
| i6017665 | | | |
| i6017673 | | | |
| i6017680 | | | |
| i6017686 | | | |
| i6017694 | | | |
| i6017703 | | | |
| i6017722 | | | |
| i6017748 | | | |
| i6017785 | | | |
| i6017792 | | | |
| i6017825 | | | |
| i6017835 | | | |
| i6017837 | | | |
| rs10500279 | 0 | 38,544,428 | |
| rs1057517909 | 0 | 38,505,400 | |
| rs1057518773 | 0 | 38,505,868 | |
| rs1057518885 | 0 | 38,561,362 | |
| rs1057518940 | 0 | 38,499,718 | |
| rs1057518970 | 0 | 38,448,398 | |
| rs1057519173 | 0 | 38,489,444 | |
| rs1057520711 | 0 | 38,580,112 | |
| rs1057523844 | 0 | 38,506,547 | |
| rs1057524858 | 0 | 38,502,728 | |
| rs1064793254 | 0 | 38,478,570 | |
| rs1064793717 | 0 | 38,483,078 | |
| rs1064793932 | 0 | 38,580,369 | |
| rs1064794572 | 0 | 38,585,066 | |
| rs1064794845 | 0 | 38,496,232 | |
| rs1064797243 | 0 | 38,587,333 | |
| rs1085307631 | 0 | 38,580,410 | |
| rs1085307909 | 0 | 38,567,912 | |
| rs111364670 | 0 | 38,510,566 | |
The RYR1 gene on chromosome 19 encodes the skeletal muscle isoform ryanodine receptor that is fundamental to the process of excitation-contraction coupling and skeletal muscle calcium homeostasis. The gene is large, comprising 106 exons and encoding a protein of 5,038 amino acids.
Mutations in the RYR1 gene have been associated with at least three diseases: malignant hyperthermia (MH), and two congenital myopathies, central core disease (CCD) and multiminicore disease (MmD). The majority of RYR1 gene mutations are missense changes identified in cases of MH and CCD, exhibiting dominant inheritance in cases of MH and both dominant and recessive inheritance in CCD.[PMID 16917943]
Note also that the vast majority of causative mutations are not included on any common DNA microarray (chip) testing platforms at the present time.
Probably the best list of causative mutations in the RYR1 gene leading to malignant hyperthermia is maintained by the European Malignant Hyperthermia Group (EMHG). Their list, modified to include each corresponding SNP rs-identifier and the microarray platform (if any) testing it, is as follows:
| Exon #
|
Nucleotide
|
Amino Acid
|
SNP Rs#
|
On microarray?
|
| 2
|
c.103T>C
|
p.Cys35Arg
|
rs193922747
|
Ancestry v2, Ancestry v2d
|
| 2
|
c.130C>T
|
p.Arg44Cys
|
rs193922748
|
Ancestry v2, Ancestry v2d
|
| 6
|
c.487C>T
|
p.Arg163Cys
|
rs118192161
|
Ancestry v2, Ancestry v2c, Ancestry v2d
|
| 6
|
c.488G>T
|
p.Arg163Leu
|
rs193922753
|
Ancestry v2, Ancestry v2d
|
| 9
|
c.742G>A
|
p.Gly248Arg
|
rs1801086
|
Ancestry v2d
|
| 9
|
c.742G>C
|
p.Gly248Arg
|
rs1801086
|
Ancestry v2d
|
| 11
|
c.982C>T
|
p.Arg328Trp
|
rs193922762
|
Ancestry v2, Ancestry v2d
|
| 11
|
c.1021G>A
|
p.Gly341Arg
|
rs121918592
|
Ancestry v2c
|
| 11
|
c.1021G>C
|
p.Gly341Arg
|
rs121918592
|
Ancestry v2c
|
| 12
|
c.1201C>T
|
p.Arg401Cys
|
rs193922764
|
|
| 12
|
c.1209C>G
|
p.Ile403Met
|
rs118192116
|
Ancestry v2, Ancestry v2c, Ancestry v2d
|
| 14
|
c.1565A>C
|
p.Tyr522Ser
|
rs118192162
|
|
| 15
|
c.1589G>A
|
p.Arg530His
|
rs111888148
|
Ancestry v2, Ancestry v2c, Ancestry v2d
|
| 15
|
c.1597C>T
|
p.Arg533Cys
|
rs193922768
|
Ancestry v2, Ancestry v2d
|
| 15
|
c.1598G>A
|
p.Arg533His
|
rs144336148
|
Ancestry v2, Ancestry v2d
|
| 15
|
c.1654C>T
|
p.Arg552Trp
|
rs193922770
|
Ancestry v2, Ancestry v2d
|
| 17
|
c.1840C>T
|
p.Arg614Cys
|
rs118192172
|
Ancestry v2, Ancestry v2c, Ancestry v2d
|
| 17
|
c.1841G>T
|
p.Arg614Leu
|
rs193922772
|
Ancestry v2d
|
| 39
|
c.6487C>T
|
p.Arg2163Cys
|
rs118192175
|
Ancestry v2c, Ancestry v2d
|
| 39
|
c.6488G>A
|
p.Arg2163His
|
rs118192163
|
Ancestry v2c, Ancestry v2d
|
| 39
|
c.6502G>A
|
p.Val2168Met
|
rs118192176
|
Ancestry v2c, Ancestry v2d
|
| 40
|
c.6617C>G
|
p.Thr2206Arg
|
rs118192177
|
Ancestry v2d
|
| 40
|
c.6617C>T
|
p.Thr2206Met
|
rs118192177
|
Ancestry v2d
|
| 43
|
c.7007G>A
|
p.Arg2336His
|
rs112563513
|
Ancestry v2, Ancestry v2dv
|
| 44
|
c.7042-7044delGAG
|
p.Gln2348del
|
rs121918596
|
Ancestry v2, Ancestry v2c, Ancestry v2d
|
| 44
|
c.7048G>A
|
p.Ala2350Thr
|
rs193922802
|
Ancestry v2, Ancestry v2c, Ancestry v2d
|
| 44
|
c.7063C>T
|
p.Arg2335Trp
|
rs193922803
|
Ancestry v2, Ancestry v2c, Ancestry v2d
|
| 44
|
c.7124G>C
|
p.Gly2375Ala
|
rs193922807
|
Ancestry v2, Ancestry v2d
|
| 45
|
c.7282G>A
|
p.Ala2428Thr
|
rs193922809
|
Ancestry v2, Ancestry v2d
|
| 45
|
c.7300G>A
|
p.Gly2434Arg
|
rs121918593
|
Ancestry v2, 23andMe v5, Ancestry v2c, Ancestry v2d
|
| 45
|
c.7304G>A
|
p.Arg2435His
|
rs28933396
|
23andMe v4, Ancestry v2c, 23andMe v3, 23andMe v1, 23andMe v2, Ancestry v2d
|
| 46
|
c.7354C>T
|
p.Arg2452Trp
|
rs118192124
|
Ancestry v2, Ancestry v2d
|
| 46
|
c.7360C>T
|
p.Arg2454Cys
|
rs193922816
|
Ancestry v2, Ancestry v2c, Ancestry v2d
|
| 46
|
c.7361G>A
|
p.Arg2454His
|
rs118192122
|
Ancestry v2, Ancestry v2c, Ancestry v2d
|
| 46
|
c.7372C>T
|
p.Arg2458Cys
|
rs28933397
|
23andMe v4, Ancestry v2, Ancestry v2c, 23andMe v3, 23andMe v1, 23andMe v2, Ancestry v2d
|
| 46
|
c.7373G>A
|
p.Arg2458His
|
rs121918594
|
Ancestry v2, Ancestry v2d
|
| 47
|
c.7522C>T
|
p.Arg2508Cys
|
rs118192178
|
|
| 47
|
c.7522C>G
|
p.Arg2508Gly
|
rs118192178
|
|
| 47
|
c.7523G>A
|
p.Arg2508His
|
rs193922818
|
Ancestry v2, Ancestry v2d
|
| 63
|
c.9310G>A
|
p.Glu3104Lys
|
rs193922832
|
|
| 87
|
c.11969G>T
|
p.Gly3990Val
|
rs193922843
|
Ancestry v2, Ancestry v2d
|
| 100
|
c.14387A>G
|
p.Tyr4796Cys
|
rs118192167
|
Ancestry v2, Ancestry v2c, Ancestry v2d
|
| 100
|
c.14477C>T
|
p.Thr4826Ile
|
rs121918595
|
Ancestry v2, Ancestry v2c, Ancestry v2d
|
| 100
|
c.14497C>T
|
p.His4833Tyr
|
rs193922876
|
Ancestry v2, Ancestry v2d
|
| 101
|
c.14512C>G
|
p.Leu4838Val
|
rs193922878
|
Ancestry v2, Ancestry v2d
|
| 101
|
c.14545G>A
|
p.Val4849Ile
|
rs118192168
|
Ancestry v2, Ancestry v2c, Ancestry v2d
|
| 101
|
c.14582G>A
|
p.Arg4861His
|
rs63749869
|
23andMe v4, Ancestry v2, 23andMe v5, Ancestry v2c, 23andMe v3, Ancestry v2d
|
| 102
|
c.14693T>C
|
p.Ile4898Thr
|
rs118192170
|
Ancestry v2, Ancestry v2d
|
Coverage (% of known variants of any magnitude in SNPedia tested by a given company/chip) for variants from this gene is shown in the following table:
SNP % is based on # of SNPs on chip vs in SNPedia (unadjusted for mutation frequency or magnitude)
|
Gene
|
| Company & chip version
|
RYR1
|
| 23andMe v5
|
10%
|
| Ancestry v2
|
46%
|
