Paralogue Annotation for RYR2 residue 433

Residue details

Gene: RYR2
Reference Sequences: LRG: LRG_402, Ensembl variant: ENST00000366574 / ENSP00000355533
Amino Acid Position: 433
Reference Amino Acid: L - Leucine
Protein Domain: Cytoplasmic region

Paralogue Variants mapped to RYR2 residue 433

Paralogue	Variant	Associated Disease	Mapping Quality	Consensus	Pubmed
RYR1	L417P	Myopathy, congenital	High	5	21911697

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	ISLSRSQHEESRTARVIRSTVFLFNRFIRG>L<DALSKKAKA----STVDLPIESVSLSLQDL	459
RYR1	LSLTRCQQEESQAARMIHSTNGLYNQFIKS>L<DSFSGKPRGSGPPAGTALPIEGVILSLQDL	447
RYR3	LTLQRCQREESQAARIIRNTTALFSQFVSG>N<-----NRTA----APITLPIEEVLQTLQDL	446
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See full Alignment of Paralogues

Known Variants in RYR2

Protein	CDS	Disease Classification	Disease	dbSNP links	Effect Prediction
p.L433P	c.1298T>C	Cardiomyopathy	ARVD/C	rs121918602	SIFT: deleterious Polyphen: possibly damaging
Reports		Cardiomyopathy	ARVD/C	Identification of mutations in the cardiac ryanodine receptor gene in families affected with arrhythmogenic right ventricular cardiomyopathy type 2 (ARVD2). Hum Mol Genet. 2001 10(3):189-94. 11159936
		Cardiomyopathy	ARVD/C	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
		Cardiomyopathy	ARVD/C	Abnormal termination of Ca2+ release is a common defect of RyR2 mutations associated with cardiomyopathies. Circ Res. 2012 110(7):968-77. 22374134
		Cardiomyopathy	ARVD/C	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
		Cardiomyopathy	ARVD/C	The cardiac ryanodine receptor N-terminal region contains an anion binding site that is targeted by disease mutations. Structure. 2013 21(8):1440-9. doi: 10.1016/j.str.2013.06.012. 23871484
		Cardiomyopathy	ARVD/C	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