Paralogue Annotation for KCNH2 residue 164

Residue details

Gene: KCNH2
Reference Sequences: LRG: LRG_288, Ensembl variant: ENST00000262186 / ENSP00000262186
Amino Acid Position: 164
Reference Amino Acid: R - Arginine
Protein Domain: N-terminus


Paralogue Variants mapped to KCNH2 residue 164

ParalogueVariantAssociated DiseaseMapping QualityConsensusPubmed
CNGB1D402NRetinitis pigmentosa, autosomal recessiveLow1 24938718

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-----------TNHRGPPTSWLAPGRAKTF>R<LKLPALLALTARESSVRSGGAGGAGAPGAV194
KCNH1--------------------------CKGW>G<------------------------------149
KCNH3--------------------------WKET>G<GGRR--------------------------153
KCNH4--------------------------GRGD>S<NHEN--------------------------154
KCNH5--------------------------TKGW>T<------------------------------147
KCNH6---------------------LAKCSSRSL>S<QRLLSQSFLGSEGSHGRPGGPG--------167
KCNH7------------N----PILPIKTVNRKFF>G<FKFPGLRVLTYRKQSLPQEDPD------VV183
KCNH8-----------------------------D>K<KEDK--------------------------149
CNGA1------------------------------>-<------------------------------
CNGA2------------------------------>-<------------------------------
CNGA3------------------------------>-<------------------------------
CNGA4------------------------------>-<------------------------------
CNGB1VTEVLLDSCVVSQVGVGQSEEDGTRPQSTS>D<QKLWEEVGEEAKKEAEEKAKEEAEEVAEEE432
CNGB3----------------SRRNEEGSHPSNQS>Q<Q----TTAQEENKGEEKSLKTKSTPVTSEE64
HCN1--------------------------PAGG>-<--F---------------------------81
HCN2--------------------------EAGS>E<EAG---------------------------150
HCN3------------------------------>-<--G---------------------------41
HCN4---------------------------AAG>D<QIL---------------------------201
cons                              > <                              

See full Alignment of Paralogues


Known Variants in KCNH2

ProteinCDSDisease ClassificationDiseasedbSNP linksEffect Prediction
p.R164Hc.491G>A Inherited ArrhythmiaLQTSrs199472866SIFT: tolerated
Polyphen: benign
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 End-recovery QTc: a useful metric for assessing genetic variants of unknown significance in long-QT syndrome. J Cardiovasc Electrophysiol. 2012 23(6):637-42. doi: 10.1111/j.1540-8167.2011.02265. 22429796
p.R164Cc.490C>T Inherited ArrhythmiaSQTSSIFT:
Polyphen:
ReportsInherited ArrhythmiaSQTS Gain-of-Function KCNH2 Mutations in Patients with Brugada Syndrome. J Cardiovasc Electrophysiol. 2014 25(5):522-30. doi: 10.1111/jce.12361. 24400717