Paralogue Annotation for RYR2 residue 419

Residue details

Gene: RYR2
Reference Sequences: LRG: LRG_402, Ensembl variant: ENST00000366574 / ENSP00000355533
Amino Acid Position: 419
Reference Amino Acid: I - Isoleucine
Protein Domain: Cytoplasmic region

Paralogue Variants mapped to RYR2 residue 419

Paralogue	Variant	Associated Disease	Mapping Quality	Consensus	Pubmed
RYR1	I403M	Central core disease	High	9	8220423, 11524458, 23422674, 9334205, 9873004

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	RKAIMHHEGHMDDGISLSRSQHEESRTARV>I<RSTVFLFNRFIRGLDALSKKAKA----STV	445
RYR1	KKAMLHQEGHMDDALSLTRCQQEESQAARM>I<HSTNGLYNQFIKSLDSFSGKPRGSGPPAGT	433
RYR3	RKVILHQEGHMDDGLTLQRCQREESQAARI>I<RNTTALFSQFVSGN-----NRTA----API	432
cons	> <

See full Alignment of Paralogues

Known Variants in RYR2

Protein	CDS	Disease Classification	Disease	dbSNP links	Effect Prediction
p.I419F	c.1255A>T	Inherited Arrhythmia	CPVT		SIFT: deleterious Polyphen: possibly damaging
Reports		Inherited Arrhythmia	CPVT	Spectrum and frequency of cardiac channel defects in swimming-triggered arrhythmia syndromes. Circulation. 2004 110(15):2119-24. 15466642
		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