Paralogue Annotation for KCNH2 residue 622

Residue details

Gene: KCNH2
Reference Sequences: LRG: LRG_288, Ensembl variant: ENST00000262186 / ENSP00000262186
Amino Acid Position: 622
Reference Amino Acid: L - Leucine
Protein Domain: Transmembrane/Linker/Pore

Paralogue Variants mapped to KCNH2 residue 622

Paralogue	Variant	Associated Disease	Mapping Quality	Consensus	Pubmed
CNGA3	L363P	Achromatopsia	High	9	20506298

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	----------LGGPSIKDKYVTALYFTFSS>L<TSVGFGNVSPNTNSEKIFSICVMLIGSLMY	652
KCNH1	---S--GK-WEGGPSKNSVYISSLYFTMTS>L<TSVGFGNIAPSTDIEKIFAVAIMMIGSLLY	491
KCNH3	SEANGTGLELLGGPSLRSAYITSLYFALSS>L<TSVGFGNVSANTDTEKIFSICTMLIGALMH	493
KCNH4	---------SVGGPSRRSAYIAALYFTLSS>L<TSVGFGNVCANTDAEKIFSICTMLIGALMH	467
KCNH5	---A--GI-WEGGPSKDSLYVSSLYFTMTS>L<TTIGFGNIAPTTDVEKMFSVAMMMVGSLLY	460
KCNH6	---P------ASGPSVQDKYVTALYFTFSS>L<TSVGFGNVSPNTNSEKVFSICVMLIGSLMY	504
KCNH7	---S------SSGPSIKDKYVTALYFTFSS>L<TSVGFGNVSPNTNSEKIFSICVMLIGSLMY	655
KCNH8	---------TLGGPSIRSAYIAALYFTLSS>L<TSVGFGNVSANTDAEKIFSICTMLIGALMH	462
CNGA1	-----------EFGRLARKYVYSLYWSTLT>L<TTIG-ETPPPVRDSEYVFVVVDFLIGVLIF	389
CNGA2	-----------EYGYLAREYIYCLYWSTLT>L<TTIG-ETPPPVKDEEYLFVIFDFLIGVLIF	364
CNGA3	-----------EHGRLSRKYIYSLYWSTLT>L<TTIG-ETPPPVKDEEYLFVVVDFLVGVLIF	392
CNGA4	-----------GFERLRRQYLYSFYFSTLI>L<TTVG-DTPPPAREEEYLFMVGDFLLAVMGF	258
CNGB1	--------------GVGNSYIRCYYFAVKT>L<ITIG-GLPDPKTLFEIVFQLLNYFTGVFAF	872
CNGB3	--------------GEGNEYLRCYYWAVRT>L<ITIG-GLPEPQTLFEIVFQLLNFFSGVFVF	434
HCN1	-----------VNDSWGKQYSYALFKAMSH>M<LCIGYGAQAPVSMSDLWITMLSMIVGATCY	386
HCN2	-----------VNHSWSELYSFALFKAMSH>M<LCIGYGRQAPESMTDIWLTMLSMIVGATCY	455
HCN3	-----------VNHSWGRQYSHALFKAMSH>M<LCIGYGQQAPVGMPDVWLTMLSMIVGATCY	339
HCN4	-----------VNNSWGKQYSYALFKAMSH>M<LCIGYGRQAPVGMSDVWLTMLSMIVGATCY	506
cons	> <

See full Alignment of Paralogues

Known Variants in KCNH2

Protein	CDS	Disease Classification	Disease	dbSNP links	Effect Prediction
p.L622F	c.1864C>T	Inherited Arrhythmia	LQTS	rs199473525	SIFT: deleterious Polyphen: probably damaging
Reports		Inherited Arrhythmia	LQTS	Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing. Heart Rhythm. 2005 2(5):507-17. 15840476