Paralogue Annotation for KCNH2 residue 640

Residue details

Gene: KCNH2
Reference Sequences: LRG: LRG_288, Ensembl variant: ENST00000262186 / ENSP00000262186
Amino Acid Position: 640
Reference Amino Acid: F - Phenylalanine
Protein Domain: Transmembrane/Linker/Pore


Paralogue Variants mapped to KCNH2 residue 640

ParalogueVariantAssociated DiseaseMapping QualityConsensusPubmed
CNGA3F380SColour-blindness, totalHigh9 11536077

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.



KCNH2KYVTALYFTFSSLTSVGFGNVSPNTNSEKI>F<SICVMLIGSLMYASIFGNVSAIIQRLYSGT670
KCNH1VYISSLYFTMTSLTSVGFGNIAPSTDIEKI>F<AVAIMMIGSLLYATIFGNVTTIFQQMYANT509
KCNH3AYITSLYFALSSLTSVGFGNVSANTDTEKI>F<SICTMLIGALMHAVVFGNVTAIIQRMYARR511
KCNH4AYIAALYFTLSSLTSVGFGNVCANTDAEKI>F<SICTMLIGALMHAVVFGNVTAIIQRMYSRR485
KCNH5LYVSSLYFTMTSLTTIGFGNIAPTTDVEKM>F<SVAMMMVGSLLYATIFGNVTTIFQQMYANT478
KCNH6KYVTALYFTFSSLTSVGFGNVSPNTNSEKV>F<SICVMLIGSLMYASIFGNVSAIIQRLYSGT522
KCNH7KYVTALYFTFSSLTSVGFGNVSPNTNSEKI>F<SICVMLIGSLMYASIFGNVSAIIQRLYSGT673
KCNH8AYIAALYFTLSSLTSVGFGNVSANTDAEKI>F<SICTMLIGALMHALVFGNVTAIIQRMYSRW480
CNGA1KYVYSLYWSTLTLTTIG-ETPPPVRDSEYV>F<VVVDFLIGVLIFATIVGNIGSMISNMNAAR407
CNGA2EYIYCLYWSTLTLTTIG-ETPPPVKDEEYL>F<VIFDFLIGVLIFATIVGNVGSMISNMNATR382
CNGA3KYIYSLYWSTLTLTTIG-ETPPPVKDEEYL>F<VVVDFLVGVLIFATIVGNVGSMISNMNASR410
CNGA4QYLYSFYFSTLILTTVG-DTPPPAREEEYL>F<MVGDFLLAVMGFATIMGSMSSVIYNMNTAD276
CNGB1SYIRCYYFAVKTLITIG-GLPDPKTLFEIV>F<QLLNYFTGVFAFSVMIGQMRDVVGAATAGQ890
CNGB3EYLRCYYWAVRTLITIG-GLPEPQTLFEIV>F<QLLNFFSGVFVFSSLIGQMRDVIGAATANQ452
HCN1QYSYALFKAMSHMLCIGYGAQAPVSMSDLW>I<TMLSMIVGATCYAMFVGHATALIQSLDSSR404
HCN2LYSFALFKAMSHMLCIGYGRQAPESMTDIW>L<TMLSMIVGATCYAMFIGHATALIQSLDSSR473
HCN3QYSHALFKAMSHMLCIGYGQQAPVGMPDVW>L<TMLSMIVGATCYAMFIGHATALIQSLDSSR357
HCN4QYSYALFKAMSHMLCIGYGRQAPVGMSDVW>L<TMLSMIVGATCYAMFIGHATALIQSLDSSR524
cons                              > <                              

See full Alignment of Paralogues


Known Variants in KCNH2

ProteinCDSDisease ClassificationDiseasedbSNP linksEffect Prediction
p.F640Lc.1920C>A Inherited ArrhythmiaLQTSSIFT: deleterious
Polyphen: probably damaging
ReportsInherited ArrhythmiaLQTS Novel KCNQ1 and HERG missense mutations in Dutch long-QT families. Hum Mutat. 1999 13(4):301-10. 10220144
Inherited ArrhythmiaLQTS The use of genotype-phenotype correlations in mutation analysis for the long QT syndrome. J Med Genet. 2003 40(2):141-5. 12566525
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
p.F640Vc.1918T>G Inherited ArrhythmiaLQTSSIFT: deleterious
Polyphen: probably damaging
ReportsInherited ArrhythmiaLQTS 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
Inherited ArrhythmiaLQTS Most LQT2 mutations reduce Kv11.1 (hERG) current by a class 2 (trafficking-deficient) mechanism. Circulation. 2006 113(3):365-73. 16432067
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 An in vivo cardiac assay to determine the functional consequences of putative long QT syndrome mutations. Circ Res. 2013 112(5):826-30. doi: 10.1161/CIRCRESAHA.112.300664. 23303164
p.Phe640Leuc.1918T>C UnknownSIFT:
Polyphen: