| Paralogue | Variant | Associated Disease | Mapping Quality | Consensus | Pubmed |
|---|---|---|---|---|---|
| RYR1 | R2435H | Central core disease | High | 9 | 8220422, 11524458, 19648156, 21965348, 9334205, 9873004, 23842196 |
| RYR1 | R2435L | Central core disease | High | 9 | 10051009, 19027160, 23558838 |
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 | TLDTEEEEDDTIHMGNAIMTFYSALIDLLG>R<CAPEMHLIHAGKGEAIRIRSILRSLIPLGD | 2431 |
| RYR1 | HFGEEPPEENRVHLGHAIMSFYAALIDLLG>R<CAPEMHLIQAGKGEALRIRAILRSLVPLED | 2465 |
| RYR3 | STGDDEEEEEIVHMGNAIMSFYSALIDLLG>R<CAPEMHLIQTGKGEAIRIRSILRSLVPTED | 2328 |
| cons | > < |
| Protein | CDS | Disease Classification | Disease | dbSNP links | Effect Prediction |
|---|---|---|---|---|---|
| p.R2401H | c.7202G>A | Inherited Arrhythmia | CPVT | SIFT: deleterious Polyphen: probably damaging | |
| Reports | Inherited Arrhythmia | CPVT | A novel mutation in FKBP12.6 binding region of the human cardiac ryanodine receptor gene (R2401H) in a Japanese patient with catecholaminergic polymorphic ventricular tachycardia. Int J Cardiol. 2005 99(2):343-5. 15749201 | ||
| 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 | |||
| Inherited Arrhythmia | CPVT | Human cardiac ryanodine receptor mutations in ion channel disorders in Japan. Int J Cardiol. 2007 116(2):263-5. 16843546 | |||
| 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 | |||
| 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 | |||
| Inherited Arrhythmia | CPVT | Germline and somatic mosaicism for a mutation of the ryanodine receptor type 2 gene: implication for genetic counselling and patient caring. Europace. 2011 13(1):130-2. doi: 10.1093/europace/euq331. 20851825 | |||
| p.R2401L | c.7202G>T | Inherited Arrhythmia | CPVT | SIFT: deleterious Polyphen: probably damaging | |
| Reports | Inherited Arrhythmia | CPVT | Identification of novel missense mutations of cardiac ryanodine receptor gene in exercise-induced sudden death at autopsy. J Mol Diagn. 2006 8(1):62-7. 16436635 | ||
| 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 | |||