Paralogue Annotation for RYR2 residue 4762

Residue details

Gene: RYR2
Reference Sequences: LRG: LRG_402, Ensembl variant: ENST00000366574 / ENSP00000355533
Amino Acid Position: 4762
Reference Amino Acid: H - Histidine
Protein Domain: Transmembrane region

Paralogue Variants mapped to RYR2 residue 4762

Paralogue	Variant	Associated Disease	Mapping Quality	Consensus	Pubmed
RYR1	H4833Y	Malignant hyperthermia	High	9	18212565, 20461000, 20482855, 23459219

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	GHYNNFFFAAHLLDIAMGFKTLRTILSSVT>H<NGKQLVLTVGLLAVVVYLYTVVAFNFFRKF	4792
RYR1	GHYNNFFFAAHLLDIAMGVKTLRTILSSVT>H<NGKQLVMTVGLLAVVVYLYTVVAFNFFRKF	4863
RYR3	GHYNNFFFAAHLLDIAMGFKTLRTILSSVT>H<NGKQLVLTVGLLAVVVYLYTVVAFNFFRKF	4695
cons	> <

See full Alignment of Paralogues

Known Variants in RYR2

Protein	CDS	Disease Classification	Disease	dbSNP links	Effect Prediction
p.H4762P	c.14285A>C	Inherited Arrhythmia	CPVT		SIFT: deleterious Polyphen: benign
Reports		Inherited Arrhythmia	CPVT	Catecholaminergic polymorphic ventricular tachycardia: RYR2 mutations, bradycardia, and follow up of the patients. J Med Genet. 2005 42(11):863-70. 16272262
		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