Paralogue Annotation for KCNH2 residue 594

Residue details

Gene: KCNH2
Reference Sequences: LRG: LRG_288, Ensembl variant: ENST00000262186 / ENSP00000262186
Amino Acid Position: 594
Reference Amino Acid: G - Glycine
Protein Domain: Transmembrane/Linker/Pore


Paralogue Variants mapped to KCNH2 residue 594

ParalogueVariantAssociated DiseaseMapping QualityConsensusPubmed
CNGA3S341PColour-blindness, totalMedium5 11536077, 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.



KCNH2WYAIGNMEQPHMDSR----IGWLHNLGDQI>G<KPYNSS----------G-------------601
KCNH1WYSIGDYEIFDEDTKTIRNNSWLYQLAMDI>G<TPYQFN--------GSG-----------S-437
KCNH3WFYIGQREIESSESELPE-IGWLQELARRL>E<TPYYLVGRRPAGGNSSGQSDNCSSSSEANG437
KCNH4WYVIGRREMEANDPLLWD-IGWLHELGKRL>E<VPYVNG------------------------415
KCNH5WYSIGDYEVIDEVTNTIQIDSWLYQLALSI>G<TPYRYN--------T-S-----------A-406
KCNH6WYAIGNVERPYLEHK----IGWLDSLGVQL>G<KRYNGS----------D-----------P-453
KCNH7WYAIGNVERPYLTDK----IGWLDSLGQQI>G<KRYNDS----------D-----------S-604
KCNH8WYVIGKMEREDNSLLKWE-VGWLHELGKRL>E<SPYYGNN-----------------------410
CNGA1FYSISKAIGFGND-------TWVYPD---I>N<DP----------------------------340
CNGA2YYAISKSIGFGVD-------TWVYPN---I>T<DP----------------------------315
CNGA3YFAISKFIGFGTD-------SWVYPN---I>S<IP----------------------------343
CNGA4YFALSRYLGFGRD-------AWVYPD---P>A<QP----------------------------209
CNGB1YYWASAYQGLGST-------HWVYD----->-<------------------------------826
CNGB3YYWASNYEGIGTT-------RWVYD----->-<------------------------------388
HCN1QFLVPLLQDFPPD-------CWVS-----L>N<EM----------------------------336
HCN2QFLVPMLQDFPRN-------CWVS-----I>N<GM----------------------------405
HCN3QFLVPMLQDFPPD-------CWVS-----I>N<HM----------------------------289
HCN4QFLVPMLQDFPDD-------CWVS-----I>N<NM----------------------------456
cons                              > <                              

See full Alignment of Paralogues


Known Variants in KCNH2

ProteinCDSDisease ClassificationDiseasedbSNP linksEffect Prediction
p.G594Dc.1781G>A Inherited ArrhythmiaLQTSSIFT: deleterious
Polyphen: possibly damaging
ReportsInherited ArrhythmiaLQTS 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 ArrhythmiaLQTS Genetic testing for long-QT syndrome: distinguishing pathogenic mutations from benign variants. Circulation. 2009 120(18):1752-60. 19841300
Inherited ArrhythmiaLQTS Phylogenetic and physicochemical analyses enhance the classification of rare nonsynonymous single nucleotide variants in type 1 and 2 long-QT syndrome. Circ Cardiovasc Genet. 2012 5(5):519-28. doi: 10.1161/CIRCGENETICS.112.963785. 22949429
Inherited ArrhythmiaLQTS 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