| Paralogue | Variant | Associated Disease | Mapping Quality | Consensus | Pubmed |
|---|---|---|---|---|---|
| RYR1 | R163C | Central core disease | High | 9 | 8220423, 11524458, 19541610, 19648156, 20461000, 21965348, 8592342, 12732639, 9502764, 23459219, 9334205, 9873004, 21156754 |
| RYR1 | R163L | Malignant hyperthermia ? | High | 9 | 16163667, 25658027 |
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 RYR2.
| RYR2 | DVGLQEDTTGEACWWTIHPASKQRSEGEKV>R<VGDDLILVSVSSERYLHLSYGNGSLHVDAA | 206 |
| RYR1 | DVGLQEDATGEACWWTMHPASKQRSEGEKV>R<VGDDIILVSVSSERYLHLSTASGELQVDAS | 193 |
| RYR3 | DVGLREHATGEACWWTIHPASKQRSEGEKV>R<IGDDLILVSVSSERYLHLSVSNGNIQVDAS | 196 |
| cons | > < |
| Protein | CDS | Disease Classification | Disease | dbSNP links | Effect Prediction |
|---|---|---|---|---|---|
| p.R176Q | c.527G>A | Cardiomyopathy | CPVT,ARVD/C | SIFT: deleterious Polyphen: probably damaging | |
| Reports | Cardiomyopathy | ARVD/C | Identification of mutations in the cardiac ryanodine receptor gene in families affected with arrhythmogenic right ventricular cardiomyopathy type 2 (ARVD2). Hum Mol Genet. 2001 10(3):189-94. 11159936 | ||
| Cardiomyopathy | ARVD/C | Enhanced store overload-induced Ca2+ release and channel sensitivity to luminal Ca2+ activation are common defects of RyR2 mutations linked to ventricular tachycardia and sudden death. Circ Res. 2005 97(11):1173-81. 16239587 | |||
| Cardiomyopathy | ARVD/C | FKBP12.6 binding of ryanodine receptors carrying mutations associated with arrhythmogenic cardiac disease. Biochem J. 2009 419(2):273-8. 19226252 | |||
| Cardiomyopathy | ARVD/C | Mice with the R176Q cardiac ryanodine receptor mutation exhibit catecholamine-induced ventricular tachycardia and cardiomyopathy. Proc Natl Acad Sci U S A. 2006 103(32):12179-84. 16873551 | |||
| Inherited Arrhythmia | CPVT | The RYR2-encoded ryanodine receptor/calcium release channel in patients diagnosed previously with either catecholaminergic polymorphic ventricular tachycardia or genotype negative, exercise-induced long QT syndrome: a comprehensive open reading frame mutational analysis. J Am Coll Cardiol. 2009 54(22):2065-74. 19926015 | |||
| Cardiomyopathy | ARVD/C | Abnormal termination of Ca2+ release is a common defect of RyR2 mutations associated with cardiomyopathies. Circ Res. 2012 110(7):968-77. 22374134 | |||
| Cardiomyopathy | ARVD/C | Type 2 ryanodine receptor domain A contains a unique and dynamic α-helix that transitions to a β-strand in a mutant linked with a heritable cardiomyopathy. J Mol Biol. 2013 425(21):4034-46. doi: 10.1016/j.jmb.2013.08.015. 23978697 | |||
| Cardiomyopathy | ARVD/C | New exome data question the pathogenicity of genetic variants previously associated with catecholaminergic polymorphic ventricular tachycardia. Circ Cardiovasc Genet. 2013 6(5):481-9. doi: 10.1161/CIRCGENETICS.113.000118. 24025405 | |||
| Inherited Arrhythmia | CPVT | Paralogue annotation identifies novel pathogenic variants in patients with Brugada syndrome and catecholaminergic polymorphic ventricular tachycardia. J Med Genet. 2014 51(1):35-44. doi: 10.1136/jmedgenet-2013-101917. 24136861 | |||
| p.Arg176Leu | c.527G>T | Unknown | SIFT: Polyphen: | ||