Paralogue Annotation for RYR2 residue 4497
Residue details
Gene: RYR2Reference Sequences: LRG:
LRG_402, Ensembl variant:
ENST00000366574 /
ENSP00000355533Amino Acid Position: 4497
Reference Amino Acid: R - Arginine
Protein Domain: Transmembrane region
Paralogue Variants mapped to RYR2 residue 4497
| Paralogue | Variant | Associated Disease | Mapping Quality | Consensus | Pubmed | | RYR1 | R4558Q | Central core disease | High | 9 |
17226826, 25637381, 26332594 |
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 | THRYGEPEVPESAFWKKIIAYQQKLLNYFA>R<NFYNMRMLALFVAFAINFILLFYKVSTSSV | 4527 |
| RYR1 | PSPPPKKEEAGGEFWGELEVQRVKFLNYLS>R<NFYTLRFLALFLAFAINFILLFYKVSDSPP | 4588 |
| RYR3 | GQKVEKPEAFTANFFKGLEIYQTKLLHYLA>R<NFYNLRFLALFVAFAINFILLFYKVTEEPL | 4438 |
| cons | > < | |
Known Variants in RYR2
| Protein | CDS | Disease Classification | Disease | dbSNP links | Effect Prediction |
|---|
| p.R4497C | c.13489C>T |
Inherited Arrhythmia | CPVT | rs121918600 | SIFT: deleterious
Polyphen: probably damaging |
| Reports | Inherited Arrhythmia | CPVT |
Mutations in the cardiac ryanodine receptor gene (hRyR2) underlie catecholaminergic polymorphic ventricular tachycardia. Circulation. 2001 103(2):196-200.
11208676 |
| Inherited Arrhythmia | CPVT |
FKBP12.6 deficiency and defective calcium release channel (ryanodine receptor) function linked to exercise-induced sudden cardiac death. Cell. 2003 113(7):829-40.
12837242 |
| Inherited Arrhythmia | CPVT |
FKBP12.6 binding of ryanodine receptors carrying mutations associated with arrhythmogenic cardiac disease. Biochem J. 2009 419(2):273-8.
19226252 |
| Inherited Arrhythmia | CPVT |
Na+-dependent SR Ca2+ overload induces arrhythmogenic events in mouse cardiomyocytes with a human CPVT mutation. Cardiovasc Res. 2010 87(1):50-9.
20080988 |
| Inherited Arrhythmia | CPVT |
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 |