Paralogue Annotation for KCNH2 residue 586

Residue details

Gene: KCNH2
Reference Sequences: LRG: LRG_288, Ensembl variant: ENST00000262186 / ENSP00000262186
Amino Acid Position: 586
Reference Amino Acid: L - Leucine
Protein Domain: Transmembrane/Linker/Pore

Paralogue Variants mapped to KCNH2 residue 586

Paralogue	Variant	Associated Disease	Mapping Quality	Consensus	Pubmed
CNGA3	V336F	Achromatopsia	Medium	8	25637600

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	IAHWLACIWYAIGNMEQPHMDSR----IGW>L<HNLGDQIGKPYNSS----------G-----	601
KCNH1	AAHWMACIWYSIGDYEIFDEDTKTIRNNSW>L<YQLAMDIGTPYQFN--------GSG-----	436
KCNH3	LAHWVACVWFYIGQREIESSESELPE-IGW>L<QELARRLETPYYLVGRRPAGGNSSGQSDNC	429
KCNH4	LAHWMACIWYVIGRREMEANDPLLWD-IGW>L<HELGKRLEVPYVNG----------------	415
KCNH5	VAHWLACIWYSIGDYEVIDEVTNTIQIDSW>L<YQLALSIGTPYRYN--------T-S-----	405
KCNH6	IAHWLACIWYAIGNVERPYLEHK----IGW>L<DSLGVQLGKRYNGS----------D-----	452
KCNH7	IAHWLACIWYAIGNVERPYLTDK----IGW>L<DSLGQQIGKRYNDS----------D-----	603
KCNH8	LAHWMACIWYVIGKMEREDNSLLKWE-VGW>L<HELGKRLESPYYGNN---------------	410
CNGA1	IIHWNACVFYSISKAIGFGND-------TW>V<YPD---INDP--------------------	340
CNGA2	IIHWNACIYYAISKSIGFGVD-------TW>V<YPN---ITDP--------------------	315
CNGA3	IIHWNACIYFAISKFIGFGTD-------SW>V<YPN---ISIP--------------------	343
CNGA4	VIHWNSCLYFALSRYLGFGRD-------AW>V<YPD---PAQP--------------------	209
CNGB1	SLHLNSCLYYWASAYQGLGST-------HW>V<YD----------------------------	826
CNGB3	ILHINACVYYWASNYEGIGTT-------RW>V<YD----------------------------	388
HCN1	LCHWDGCLQFLVPLLQDFPPD-------CW>V<S-----LNEM--------------------	336
HCN2	LCHWDGCLQFLVPMLQDFPRN-------CW>V<S-----INGM--------------------	405
HCN3	LCHWDGCLQFLVPMLQDFPPD-------CW>V<S-----INHM--------------------	289
HCN4	LCHWDGCLQFLVPMLQDFPDD-------CW>V<S-----INNM--------------------	456
cons	> <

See full Alignment of Paralogues

Known Variants in KCNH2

Protein	CDS	Disease Classification	Disease	dbSNP links	Effect Prediction
p.L586M	c.1756C>A	Inherited Arrhythmia	LQTS		SIFT: Polyphen:
Reports		Inherited Arrhythmia	LQTS	Sodium-channel blockers might contribute to the prevention of ventricular tachycardia in patients with long QT syndrome type 2: a description of 4 cases. J Electrocardiol. 2012 45(3):237-43. 22402334