| Paralogue | Variant | Associated Disease | Mapping Quality | Consensus | Pubmed |
|---|---|---|---|---|---|
| RYR2 | R4822H | Catecholaminergic polymorphic ventricular tachycar | High | 9 | 19926015, 24025405, 24136861 |
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 RYR1.
| RYR1 | FYNKSEDEDEPDMKCDDMMTCYLFHMYVGV>R<AGGGIGDEIEDPAGDEYELYRVVFDITFFF | 4923 |
| RYR2 | FYNKSEDGDTPDMKCDDMLTCYMFHMYVGV>R<AGGGIGDEIEDPAGDEYEIYRIIFDITFFF | 4852 |
| RYR3 | FYNKSEDDDEPDMKCDDMMTCYLFHMYVGV>R<AGGGIGDEIEDPAGDPYEMYRIVFDITFFF | 4755 |
| cons | > < |
| Protein | CDS | Disease Classification | Disease | dbSNP links | Effect Prediction |
|---|---|---|---|---|---|
| p.R4893W | c.14677C>T | Other Myopathy | rs118192150 | SIFT: Polyphen: | |
| Reports | Other Myopathy | Familial and sporadic forms of central core disease are associated with mutations in the C-terminal domain of the skeletal muscle ryanodine receptor. Hum Mol Genet. 2001 10(22):2581-92. 11709545 | |||
| Other Myopathy | The pore region of the skeletal muscle ryanodine receptor is a primary locus for excitation-contraction uncoupling in central core disease. J Gen Physiol. 2003 121(4):277-86. 12642598 | ||||
| Other Myopathy | Central core disease mutations R4892W, I4897T and G4898E in the ryanodine receptor isoform 1 reduce the Ca2+ sensitivity and amplitude of Ca2+-dependent Ca2+ release. Biochem J. 2004 382(Pt 2):557-64. 15175001 | ||||
| Other Myopathy | Effect of ryanodine receptor mutations on interleukin-6 release and intracellular calcium homeostasis in human myotubes from malignant hyperthermia-susceptible individuals and patients affected by central core disease. J Biol Chem. 2004 279(42):43838-46. 15299003 | ||||
| Other Myopathy | Ca2+ release in muscle fibers expressing R4892W and G4896V type 1 ryanodine receptor disease mutants. PLoS One. 2013 8(1):e54042. doi: 10.1371/journal.pone.0054042. 23308296 | ||||
| Unknown | Clinical utility gene card for: Multi-minicore disease. Eur J Hum Genet. 2012 20(2). doi: 10.1038/ejhg.2011.180. 22009146 | ||||
| Other Myopathy | Ryanodine myopathies without central cores--clinical, histopathologic, and genetic description of three cases. Pediatr Neurol. 2014 51(2):275-8. doi: 10.1016/j.pediatrneurol.2014.04. 24950660 | ||||
| p.R4893Q | c.14678G>A | Other Myopathy | rs118192151 | SIFT: Polyphen: | |
| Reports | Other Myopathy | Principal mutation hotspot for central core disease and related myopathies in the C-terminal transmembrane region of the RYR1 gene. Neuromuscul Disord. 2003 13(2):151-7. 12565913 | |||
| Other Myopathy | Clinical features and ryanodine receptor type 1 gene mutation analysis in a Chinese family with central core disease. J Child Neurol. 2013 28(3):384-8. doi: 10.1177/0883073812441251. 22550088 | ||||
| Unknown | Clinical utility gene card for: Multi-minicore disease. Eur J Hum Genet. 2012 20(2). doi: 10.1038/ejhg.2011.180. 22009146 | ||||
| p.R4893P | c.14678G>C | Other Myopathy | rs118192151 | SIFT: Polyphen: | |
| Reports | Other Myopathy | Central core disease is due to RYR1 mutations in more than 90% of patients. Brain. 2006 129(Pt 6):1470-80. 16621918 | |||
| Unknown | Clinical utility gene card for: Multi-minicore disease. Eur J Hum Genet. 2012 20(2). doi: 10.1038/ejhg.2011.180. 22009146 | ||||
| p.R4893G | c.14677C>G | Putative Benign | rs118192150 | SIFT: Polyphen: benign | |