Paralogue | Variant | Associated Disease | Mapping Quality | Consensus | Pubmed |
---|---|---|---|---|---|
RYR2 | R176Q | Arrhythmogenic right ventricular dysplasia type 2 | High | 9 | 11159936, 16239587, 16873551, 19226252, 22374134, 23978697, 24025405, 24136861 |
To assess whether the paralogue annotation here confidently predicts that variation at this residue is pathogenic, it is important to check the reports in the Pubmed links above to ascertain that the mutations in these paralogues have been proved likely to be disease-causing. It is also important to check that the direction of effect of the variant in the paralogue is compatible with your observed phenotype in RYR1.
RYR1 | DVGLQEDATGEACWWTMHPASKQRSEGEKV>R<VGDDIILVSVSSERYLHLSTASGELQVDAS | 193 |
RYR2 | DVGLQEDTTGEACWWTIHPASKQRSEGEKV>R<VGDDLILVSVSSERYLHLSYGNGSLHVDAA | 206 |
RYR3 | DVGLREHATGEACWWTIHPASKQRSEGEKV>R<IGDDLILVSVSSERYLHLSVSNGNIQVDAS | 196 |
cons | > < |
Protein | CDS | Disease Classification | Disease | dbSNP links | Effect Prediction |
---|---|---|---|---|---|
p.R163C | c.487C>T | Other Myopathy | rs118192161 | SIFT: Polyphen: | |
Reports | Other Myopathy | Mutations in the ryanodine receptor gene in central core disease and malignant hyperthermia. Nat Genet. 1993 5(1):51-5. 8220423 | |||
Other Myopathy | Functional effects of central core disease mutations in the cytoplasmic region of the skeletal muscle ryanodine receptor. J Gen Physiol. 2001 118(3):277-90. 11524458 | ||||
Other Myopathy | Crystal structure of type I ryanodine receptor amino-terminal beta-trefoil domain reveals a disease-associated mutation "hot spot" loop. Proc Natl Acad Sci U S A. 2009 106(27):11040-4. doi: 10.1073/pnas.0905186106. 19541610 | ||||
Other Myopathy | Genetic variation in RYR1 and malignant hyperthermia phenotypes. Br J Anaesth. 2009 103(4):538-48. doi: 10.1093/bja/aep204. 19648156 | ||||
Other Myopathy | Functional studies of RYR1 mutations in the skeletal muscle ryanodine receptor using human RYR1 complementary DNA. Anesthesiology. 2010 112(6):1350-4. doi: 10.1097/ALN.0b013e3181d69283. 20461000 | ||||
Other Myopathy | Screening of the ryanodine 1 gene for malignant hyperthermia causative mutations by high resolution melt curve analysis. Anesth Analg. 2011 113(5):1120-8. 21965348 | ||||
Other Myopathy | Exclusion of defects in the skeletal muscle specific regions of the DHPR alpha 1 subunit as frequent causes of malignant hyperthermia. J Med Genet. 1995 32(11):913-4. 8592342 | ||||
Other Myopathy | Functional defects in six ryanodine receptor isoform-1 (RyR1) mutations associated with malignant hyperthermia and their impact on skeletal excitation-contraction coupling. J Biol Chem. 2003 278(28):25722-30. 12732639 | ||||
Other Myopathy | Intracellular calcium homeostasis in human primary muscle cells from malignant hyperthermia-susceptible and normal individuals. Effect Of overexpression of recombinant wild-type and Arg163Cys mutated ryanodine receptors. J Clin Invest. 1998 101(6):1233-42. 9502764 | ||||
Other Myopathy | Skeletal muscle ryanodine receptor mutations associated with malignant hyperthermia showed enhanced intensity and sensitivity to triggering drugs when expressed in human embryonic kidney cells. Anesthesiology. 2013 119(1):111-8. doi: 10.1097/ALN.0b013e31828cebfe. 23459219 | ||||
Other Myopathy | Caffeine and halothane sensitivity of intracellular Ca2+ release is altered by 15 calcium release channel (ryanodine receptor) mutations associated with malignant hyperthermia and/or central core disease. J Biol Chem. 1997 272(42):26332-9. 9334205 | ||||
Other Myopathy | Measurement of resting cytosolic Ca2+ concentrations and Ca2+ store size in HEK-293 cells transfected with malignant hyperthermia or central core disease mutant Ca2+ release channels. J Biol Chem. 1999 274(2):693-702. 9873004 | ||||
Unknown | ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing. Genet Med. 2013 15(7):565-74. doi: 10.1038/gim.2013.73. 23788249 | ||||
Unknown | A search for three known RYR1 gene mutations in 41 Swedish families with predisposition to malignant hyperthermia. Clin Genet. 1995 48(1):12-6. 7586638 | ||||
Unknown | Malignant hyperthermia and apparent heat stroke. JAMA. 2001 286(2):168-9. 11448278 | ||||
Unknown | Clinical utility gene card for: Multi-minicore disease. Eur J Hum Genet. 2012 20(2). doi: 10.1038/ejhg.2011.180. 22009146 | ||||
Other Myopathy | Functional and biochemical properties of ryanodine receptor type 1 channels from heterozygous R163C malignant hyperthermia-susceptible mice. Mol Pharmacol. 2011 79(3):420-31. doi: 10.1124/mol.110.067959. 21156754 | ||||
p.R163L | c.488G>T | Other Myopathy | rs193922753 | SIFT: Polyphen: | |
Reports | Other Myopathy | Correlations between genotype and pharmacological, histological, functional, and clinical phenotypes in malignant hyperthermia susceptibility. Hum Mutat. 2005 26(5):413-25. 16163667 | |||
Other Myopathy | Next-generation Sequencing of RYR1 and CACNA1S in Malignant Hyperthermia and Exertional Heat Illness. Anesthesiology. 2015 122(5):1033-46. doi: 10.1097/ALN.0000000000000610. 25658027 | ||||
p.R163H | c.488G>A | Putative Benign | SIFT: Polyphen: |