| Paralogue | Variant | Associated Disease | Mapping Quality | Consensus | Pubmed |
|---|---|---|---|---|---|
| RYR1 | R2508G | Central core disease | High | 9 | 16621918, 20142353, 16732084, 26381711 |
| RYR1 | R2508C | Central core disease | High | 9 | 16621918, 19685112, 16732084 |
| RYR1 | R2508H | Central core disease | High | 9 | 16621918, 16732084, 23558838, 26381711 |
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 | TIAKDGNVVEPDMSAGFCPDHKAAMVLFLD>R<VYGIEVQDFLLHLLEVGFLPDLRAAASLDT | 2504 |
| RYR1 | TLGKDGALVQPKMSASFVPDHKASMVLFLD>R<VYGIENQDFLLHVLDVGFLPDMRAAASLDT | 2538 |
| RYR3 | SLNKDGSVSEPDMAANFCPDHKAPMVLFLD>R<VYGIKDQTFLLHLLEVGFLPDLRASASLDT | 2401 |
| cons | > < |
| Protein | CDS | Disease Classification | Disease | dbSNP links | Effect Prediction |
|---|---|---|---|---|---|
| p.R2474S | c.7422G>C | Inherited Arrhythmia | CPVT | rs121918598 | SIFT: tolerated 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 | 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 | |||
| Inherited Arrhythmia | CPVT | Leaky Ca2+ release channel/ryanodine receptor 2 causes seizures and sudden cardiac death in mice. J Clin Invest. 2008 118(6):2230-45. 18483626 | |||
| Inherited Arrhythmia | CPVT | Clinical and molecular characterization of patients with catecholaminergic polymorphic ventricular tachycardia. Circulation. 2002 106(1):69-74. 12093772 | |||
| Inherited Arrhythmia | CPVT | Calcium leak through ryanodine receptors leads to atrial fibrillation in 3 mouse models of catecholaminergic polymorphic ventricular tachycardia. Circ Res. 2012 111(6):708-17. doi: 10.1161/CIRCRESAHA.112.273342. 22828895 | |||
| 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 | |||
| p.R2474G | c.7420A>G | Inherited Arrhythmia | CPVT | SIFT: deleterious Polyphen: probably damaging | |
| Reports | Inherited Arrhythmia | CPVT | Genetic background of catecholaminergic polymorphic ventricular tachycardia in Japan. Circ J. 2013 77(7):1705-13. 23595086 | ||