Paralogue Annotation for RYR2 residue 2168

Residue details

Gene: RYR2
Reference Sequences: LRG: LRG_402, Ensembl variant: ENST00000366574 / ENSP00000355533
Amino Acid Position: 2168
Reference Amino Acid: H - Histidine
Protein Domain: Cytoplasmic region


Paralogue Variants mapped to RYR2 residue 2168

ParalogueVariantAssociated DiseaseMapping QualityConsensusPubmed
RYR1H2204QMultiminicore/minicore/multicore diseaseHigh9 21674524

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.



RYR2EEKLMIRGLGDIMNNKVFYQHPNLMRALGM>H<ETVMEVMVNVLGGGESKEITFPKMVANCCR2198
RYR1EENLMIQSIGNIMNNKVFYQHPNLMRALGM>H<ETVMEVMVNVLGGGESKEIRFPKMVTSCCR2234
RYR3EELLMINGLGDIMNNKVFYQHPNLMRVLGM>H<ETVMEVMVNVLGT-EKSQIAFPKMVASCCR2095
cons                              > <                              

See full Alignment of Paralogues


Known Variants in RYR2

ProteinCDSDisease ClassificationDiseasedbSNP linksEffect Prediction
p.H2168Qc.6504C>G Inherited ArrhythmiaCPVTSIFT: tolerated
Polyphen: probably damaging
ReportsInherited 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
Inherited ArrhythmiaCPVT 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