Paralogue Annotation for KCNH2 residue 616

Residue details

Gene: KCNH2
Reference Sequences: LRG: LRG_288, Ensembl variant: ENST00000262186 / ENSP00000262186
Amino Acid Position: 616
Reference Amino Acid: Y - Tyrosine
Protein Domain: Transmembrane/Linker/Pore

Paralogue Variants mapped to KCNH2 residue 616

Paralogue	Variant	Associated Disease	Mapping Quality	Consensus	Pubmed
CNGA3	Y357C	Oligocone trichromacy	High	9	21268679, 24504161

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	----------------LGGPSIKDKYVTAL>Y<FTFSSLTSVGFGNVSPNTNSEKIFSICVML	646
KCNH1	---------S--GK-WEGGPSKNSVYISSL>Y<FTMTSLTSVGFGNIAPSTDIEKIFAVAIMM	485
KCNH3	DNCSSSSEANGTGLELLGGPSLRSAYITSL>Y<FALSSLTSVGFGNVSANTDTEKIFSICTML	487
KCNH4	---------------SVGGPSRRSAYIAAL>Y<FTLSSLTSVGFGNVCANTDAEKIFSICTML	461
KCNH5	---------A--GI-WEGGPSKDSLYVSSL>Y<FTMTSLTTIGFGNIAPTTDVEKMFSVAMMM	454
KCNH6	---------P------ASGPSVQDKYVTAL>Y<FTFSSLTSVGFGNVSPNTNSEKVFSICVML	498
KCNH7	---------S------SSGPSIKDKYVTAL>Y<FTFSSLTSVGFGNVSPNTNSEKIFSICVML	649
KCNH8	---------------TLGGPSIRSAYIAAL>Y<FTLSSLTSVGFGNVSANTDAEKIFSICTML	456
CNGA1	-----------------EFGRLARKYVYSL>Y<WSTLTLTTIG-ETPPPVRDSEYVFVVVDFL	383
CNGA2	-----------------EYGYLAREYIYCL>Y<WSTLTLTTIG-ETPPPVKDEEYLFVIFDFL	358
CNGA3	-----------------EHGRLSRKYIYSL>Y<WSTLTLTTIG-ETPPPVKDEEYLFVVVDFL	386
CNGA4	-----------------GFERLRRQYLYSF>Y<FSTLILTTVG-DTPPPAREEEYLFMVGDFL	252
CNGB1	--------------------GVGNSYIRCY>Y<FAVKTLITIG-GLPDPKTLFEIVFQLLNYF	866
CNGB3	--------------------GEGNEYLRCY>Y<WAVRTLITIG-GLPEPQTLFEIVFQLLNFF	428
HCN1	-----------------VNDSWGKQYSYAL>F<KAMSHMLCIGYGAQAPVSMSDLWITMLSMI	380
HCN2	-----------------VNHSWSELYSFAL>F<KAMSHMLCIGYGRQAPESMTDIWLTMLSMI	449
HCN3	-----------------VNHSWGRQYSHAL>F<KAMSHMLCIGYGQQAPVGMPDVWLTMLSMI	333
HCN4	-----------------VNNSWGKQYSYAL>F<KAMSHMLCIGYGRQAPVGMSDVWLTMLSMI	500
cons	> <

See full Alignment of Paralogues

Known Variants in KCNH2

Protein	CDS	Disease Classification	Disease	dbSNP links	Effect Prediction
p.Y616C	c.1847A>G	Inherited Arrhythmia	LQTS	rs199472946	SIFT: deleterious Polyphen: probably damaging
Reports		Inherited Arrhythmia	LQTS	Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION long QT syndrome genetic test. Heart Rhythm. 2009 6(9):1297-303. 19716085
		Inherited Arrhythmia	LQTS	Large-scale mutational analysis of Kv11.1 reveals molecular insights into type 2 long QT syndrome. Nat Commun. 2014 5:5535. doi: 10.1038/ncomms6535. 25417810