Paralogue Annotation for RYR2 residue 176

Residue details

Gene: RYR2
Reference Sequences: LRG: LRG_402, Ensembl variant: ENST00000366574 / ENSP00000355533
Amino Acid Position: 176
Reference Amino Acid: R - Arginine
Protein Domain: Cytoplasmic region

Paralogue Variants mapped to RYR2 residue 176

ParalogueVariantAssociated DiseaseMapping QualityConsensusPubmed
RYR1R163CCentral core diseaseHigh9 8220423, 11524458, 19541610, 19648156, 20461000, 21965348, 8592342, 12732639, 9502764, 23459219, 9334205, 9873004, 21156754
RYR1R163LMalignant hyperthermia ?High9 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.

cons                              > <                              

See full Alignment of Paralogues

Known Variants in RYR2

ProteinCDSDisease ClassificationDiseasedbSNP linksEffect Prediction
p.R176Qc.527G>A CardiomyopathyCPVT,ARVD/CSIFT: deleterious
Polyphen: probably damaging
ReportsCardiomyopathyARVD/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
CardiomyopathyARVD/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
CardiomyopathyARVD/C FKBP12.6 binding of ryanodine receptors carrying mutations associated with arrhythmogenic cardiac disease. Biochem J. 2009 419(2):273-8. 19226252
CardiomyopathyARVD/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 ArrhythmiaCPVT 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
CardiomyopathyARVD/C Abnormal termination of Ca2+ release is a common defect of RyR2 mutations associated with cardiomyopathies. Circ Res. 2012 110(7):968-77. 22374134
CardiomyopathyARVD/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
CardiomyopathyARVD/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 ArrhythmiaCPVT 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.Arg176Leuc.527G>T UnknownSIFT: