Paralogue Annotation for KCNH2 residue 525

Residue details

Gene: KCNH2
Reference Sequences: LRG: LRG_288, Ensembl variant: ENST00000262186 / ENSP00000262186
Amino Acid Position: 525
Reference Amino Acid: K - Lysine
Protein Domain: Transmembrane/Linker/Pore

Paralogue Variants mapped to KCNH2 residue 525

Paralogue	Variant	Associated Disease	Mapping Quality	Consensus	Pubmed
CNGA3	R277G	Achromatopsia	Medium	6	20506298
CNGA3	R277C	Colour-blindness, total	Medium	6	11536077, 20238023, 21911670, 15743887, 23082193, 26992781
CNGA3	R277H	Colour-blindness, total	Medium	6	11536077, 23972307, 26992781
CNGB1	R765C	Retinitis pigmentosa	Medium	6	23484092
CNGB1	R765L	Retinitis pigmentosa & rod cone dystrophy	Medium	6	26355662

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 KCNH2.

KCNH2	-------------------------LIGLL>K<TARLLRLVRVARKLDRY-----SEYGAAV-	549
KCNH1	KIGFADQ---IPPPLEGRESQGISSLFSSL>K<VVRLLRLGRVARKLDHY-----IEYGAAV-	378
KCNH3	------V---Y-------------FGAHLL>K<TVRLLRLLRLLPRLDRY-----SQYSAVV-	359
KCNH4	------V---T-------------SLVHLL>K<TVRLLRLLRLLQKLERY-----SQCSAVV-	361
KCNH5	----------------------ISSLFSSL>K<VVRLLRLGRVARKLDHY-----LEYGAAV-	348
KCNH6	------T---T-------------TLIGLL>K<TARLLRLVRVARKLDRY-----SEYGAAV-	400
KCNH7	------T---T-------------TLIGLL>K<TARLLRLVRVARKLDRY-----SEYGAAV-	551
KCNH8	------V---V-------------SLVHLL>K<TVRLLRLLRLLQKLDRY-----SQHSTIV-	355
CNGA1	------------------------PEIRLN>R<LLRFSRMFEFFQRTETR-----TNYPNIFR	299
CNGA2	------------------------PEVRFN>R<LLHFARMFEFFDRTETR-----TNYPNIFR	274
CNGA3	------------------------PEVRFN>R<LLKFSRLFEFFDRTETR-----TNYPNMFR	302
CNGA4	------------------------PTLRLN>R<FLRAPRLFEAFDRTETR-----TAYPNAFR	168
CNGB1	------------------------PLLRLP>R<CLKYMAFFEFNSRLESI-----LSKAYVYR	790
CNGB3	------------------------PMFRAN>R<MLKYTSFFEFNHHLESI-----MDKAYIYR	352
HCN1	ARALR-IVRFT-------------KILSLL>R<LLRLSRLIRYIHQWEEIFHMTYDLASAVVR	297
HCN2	ARALR-IVRFT-------------KILSLL>R<LLRLSRLIRYIHQWEEIFHMTYDLASAVMR	366
HCN3	ARALR-IVRFT-------------KILSLL>R<LLRLSRLIRYIHQWEEIFHMTYDLASAVVR	250
HCN4	ARALR-IVRFT-------------KILSLL>R<LLRLSRLIRYIHQWEEIFHMTYDLASAVVR	417
cons	> <

See full Alignment of Paralogues

Known Variants in KCNH2

Protein	CDS	Disease Classification	Disease	dbSNP links	Effect Prediction
p.K525N	c.1575G>T	Inherited Arrhythmia	LQTS	rs199472913	SIFT: deleterious Polyphen: probably damaging
Reports		Inherited Arrhythmia	LQTS	Spectrum of pathogenic mutations and associated polymorphisms in a cohort of 44 unrelated patients with long QT syndrome. Clin Genet. 2006 70(3):214-27. 16922724