Paralogue Annotation for KCNH2 residue 402

Residue details

Gene: KCNH2
Reference Sequences: LRG: LRG_288, Ensembl variant: ENST00000262186 / ENSP00000262186
Amino Acid Position: 402
Reference Amino Acid: H - Histidine
Protein Domain: N-terminus

Paralogue Variants mapped to KCNH2 residue 402

Paralogue	Variant	Associated Disease	Mapping Quality	Consensus	Pubmed
CNGA3	P163L	Colour-blindness, total	Medium	9	9662398, 23105016
CNGA1	P160L	Usher syndrome	Medium	9	26338283

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	QVL---SLGADVL-PEYKLQAPRIHRWTIL>H<YSPFKA-VWDWLILLLVIYTAVFTPYSAAF	431
KCNH1	EVL---QLGSDIL-PQYKQEAPKTPPHIIL>H<YCVFKT-TWDWIILILTFYTAILVPYNVSF	241
KCNH3	KGV---FGEKPNL-PEYKVAAIRKSPFILL>H<CGALRA-TWDGFILLATLYVAVTVPYSVCV	248
KCNH4	NNV---FEPKPSV-PEYKVASVGGSRCLLL>H<YSVSKA-IWDGLILLATFYVAVTVPYNVCF	250
KCNH5	EVL---QLGSDIL-PQYKQEAPKTPPHIIL>H<YCAFKT-TWDWVILILTFYTAIMVPYNVSF	238
KCNH6	QVL---SLGADVL-PEYKLQAPRIHRWTIL>H<YSPFKA-VWDWLILLLVIYTAVFTPYSAAF	280
KCNH7	QVL---SLGADVL-PEYKLQTPRINKFTIL>H<YSPFKA-VWDWLILLLVIYTAIFTPYSAAF	431
KCNH8	NNV---FVDKPAF-PEYKVSDAKKSKFILL>H<FSTFKA-GWDWLILLATFYVAVTVPYNVCF	245
CNGA1	KD-KEKKKK--EEKSKDKKEEEKKEVVVID>P<SGNTYY-NWLFCITLPVMYNWTMVIARACF	189
CNGA2	------------KDGEDKGTKKKFELFVLD>P<AGDWYY-CWLFVIAMPVLYNWCLLVARACF	164
CNGA3	PLAKCNTNTSNN-TEEE-KKTKKKDAIVVD>P<SSNLYY-RWLTAIALPVFYNWYLLICRACF	192
CNGA4	--------------SPPAPSKARKLLPVLD>P<SGDYYY-WWLNTMVFPVMYNLIILVCRACF	58
CNGB1	MLC----CKFKHR-PW----KKYQFPQSID>P<LTNLMYVLWLFFVVMAWNWNCWLIPVRWAF	680
CNGB3	LLW----FKVKKM-PLTEYLKRIKLPNSID>S<YTDRLYLLWLLLVTLAYNWNCCFIPLRLVF	242
HCN1	LRM---FGSQKAV-EKEQERVKTAGFWIIH>P<YSDFRF-YWDLIMLIMMVGNLVIIPVGITF	166
HCN2	LRM---FGSQKAV-EREQERVKSAGAWIIH>P<YSDFRF-YWDFTMLLFMVGNLIIIPVGITF	235
HCN3	LRV---FGSHKAV-EIEQERVKSAGAWIIH>P<YSDFRF-YWDLIMLLLMVGNLIVLPVGITF	117
HCN4	LRM---FGSQKAV-EREQERVKSAGFWIIH>P<YSDFRF-YWDLTMLLLMVGNLIIIPVGITF	286
cons	> <

See full Alignment of Paralogues

Known Variants in KCNH2

Protein	CDS	Disease Classification	Disease	dbSNP links	Effect Prediction
p.H402R	c.1205A>G	Inherited Arrhythmia	LQTS	rs199473506	SIFT: deleterious Polyphen: probably damaging
Reports		Inherited Arrhythmia	LQTS	Novel mutation (H402R) in the S1 domain of KCNH2-encoded gene associated with long QT syndrome in a Spanish family. Int J Cardiol. 2010 142(2):206-8. 19136169
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