Paralogue Annotation for RYR1 residue 4898

Residue details

Gene: RYR1
Reference Sequences: Ensembl variant: ENST00000359596 / ENSP00000352608
Amino Acid Position: 4898
Reference Amino Acid: I - Isoleucine
Protein Domain:

Paralogue Variants mapped to RYR1 residue 4898

Paralogue	Variant	Associated Disease	Mapping Quality	Consensus	Pubmed
RYR3	I4730T	Schizophrenia	High	9	24463507

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	EDEDEPDMKCDDMMTCYLFHMYVGVRAGGG>I<GDEIEDPAGDEYELYRVVFDITFFFFVIVI	4928
RYR2	EDGDTPDMKCDDMLTCYMFHMYVGVRAGGG>I<GDEIEDPAGDEYEIYRIIFDITFFFFVIVI	4857
RYR3	EDDDEPDMKCDDMMTCYLFHMYVGVRAGGG>I<GDEIEDPAGDPYEMYRIVFDITFFFFVIVI	4760
cons	> <

See full Alignment of Paralogues

Known Variants in RYR1

Protein	CDS	Disease Classification	Disease	dbSNP links	Effect Prediction
p.I4898T	c.14693T>C	Other Myopathy		rs118192170	SIFT: Polyphen:
Reports		Other Myopathy		A mutation in the transmembrane/luminal domain of the ryanodine receptor is associated with abnormal Ca2+ release channel function and severe central core disease. Proc Natl Acad Sci U S A. 1999 96(7):4164-9. 10097181
		Other Myopathy		Excitation--contraction uncoupling by a human central core disease mutation in the ryanodine receptor. Proc Natl Acad Sci U S A. 2001 98(7):4215-20. 11274444
		Other Myopathy		Functional studies of RYR1 mutations in the skeletal muscle ryanodine receptor using human RYR1 complementary DNA. Anesthesiology. 2010 112(6):1350-4. doi: 10.1097/ALN.0b013e3181d69283. 20461000
		Other Myopathy		De novo RYR1 heterozygous mutation (I4898T) causing lethal core-rod myopathy in twins. Eur J Med Genet. 2011 54(1):29-33. doi: 10.1016/j.ejmg.2010.09.009. 20888934
		Other Myopathy		The I4895T mutation in the type 1 ryanodine receptor induces fiber-type specific alterations in skeletal muscle that mimic premature aging. Aging Cell. 2010 9(6):958-70. doi: 10.1111/j.1474-9726.2010.00623.x 20961389
		Other Myopathy		Calcitonin gene-related peptide restores disrupted excitation-contraction coupling in myotubes expressing central core disease mutations in RyR1. J Physiol. 2011 589(Pt 19):4649-69. doi: 10.1113/jphysiol.2011.210 21825032
		Other Myopathy		Type 1 ryanodine receptor knock-in mutation causing central core disease of skeletal muscle also displays a neuronal phenotype. Proc Natl Acad Sci U S A. 2012 109(2):610-5. doi: 10.1073/pnas.1115111108. 22203976
		Other Myopathy		Altered ryanodine receptor function in central core disease: leaky or uncoupled Ca(2+) release channels? Trends Cardiovasc Med. 2002 12(5):189-97. 12161072
		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
		Unknown		Identification of four novel mutations in the C-terminal membrane spanning domain of the ryanodine receptor 1: association with central core disease and alteration of calcium homeostasis. Hum Mol Genet. 2001 10(25):2879-87. 11741831
		Other Myopathy		Silent polymorphisms in the RYR1 gene do not modify the phenotype of the p.4898 I>T pathogenic mutation in central core disease: a case report. BMC Res Notes. 2014 7:487. doi: 10.1186/1756-0500-7-487. 25084811