| Paralogue | Variant | Associated Disease | Mapping Quality | Consensus | Pubmed |
|---|---|---|---|---|---|
| RYR2 | P4902L | Ventricular tachycardia, polymorphic | High | 9 | 14571276, 24025405 |
| RYR2 | P4902S | Catecholaminergic polymorphic ventricular tachycar | High | 9 | 16272262, 22383456, 24025405 |
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 | ELRDQQEQVKEDMETKCFICGIGSDYFDTT>P<HGFETHTLEEHNLANYMFFLMYLINKDETE | 5003 |
| RYR2 | ELRDQQEQVKEDMETKCFICGIGNDYFDTV>P<HGFETHTLQEHNLANYLFFLMYLINKDETE | 4932 |
| RYR3 | ELRDQQEQVREDMETKCFICGIGNDYFDTT>P<HGFETHTLQEHNLANYLFFLMYLINKDETE | 4835 |
| cons | > < |
| Protein | CDS | Disease Classification | Disease | dbSNP links | Effect Prediction |
|---|---|---|---|---|---|
| p.P4973L | c.14918C>T | Other Myopathy | rs146876145 | SIFT: Polyphen: | |
| Reports | Other Myopathy | Mutations in the RYR1 gene in Italian patients at risk for malignant hyperthermia: evidence for a cluster of novel mutations in the C-terminal region. Cell Calcium. 2002 32(3):143-51. 12208234 | |||
| Other Myopathy | Ryanodine receptor type 1 gene variants in the malignant hyperthermia-susceptible population of the United States. Anesth Analg. 2013 116(5):1078-86. doi: 10.1213/ANE.0b013e31828a71ff. 23558838 | ||||
| Unknown | Actionable exomic incidental findings in 6503 participants: challenges of variant classification. Genome Res. 2015 25(3):305-15. doi: 10.1101/gr.183483.114. 25637381 | ||||
| Other Myopathy | Centronuclear myopathies: genotype-phenotype correlation and frequency of defined genetic forms in an Italian cohort. J Neurol. 2015 262(7):1728-40. doi: 10.1007/s00415-015-7757-9. 25957634 | ||||
| p.P4973S | c.14917C>T | Putative Benign | SIFT: Polyphen: | ||