Paralogue Annotation for KCNE2 residue 57

Residue details

Gene: KCNE2
Reference Sequences: LRG: LRG_291, Ensembl variant: ENST00000290310 / ENSP00000290310
Amino Acid Position: 57
Reference Amino Acid: I - Isoleucine
Protein Domain: Transmembrane region

Paralogue Variants mapped to KCNE2 residue 57

ParalogueVariantAssociated DiseaseMapping QualityConsensusPubmed
KCNE3M65TArrhythmiaMedium9 24082139

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 KCNE2.

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See full Alignment of Paralogues

Known Variants in KCNE2

ProteinCDSDisease ClassificationDiseasedbSNP linksEffect Prediction
p.I57Tc.170T>C ConflictSIFT: deleterious
Polyphen: probably damaging
ReportsOther Cardiac Phenotype MiRP1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia. Cell. 1999 97(2):175-87. 10219239
Other Cardiac Phenotype A common polymorphism associated with antibiotic-induced cardiac arrhythmia. Proc Natl Acad Sci U S A. 2000 97(19):10613-8. 10984545
Inherited ArrhythmiaLQTS Genetic variations of KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 in drug-induced long QT syndrome patients. J Mol Med (Berl). 2004 82(3):182-8. 14760488
Inherited ArrhythmiaLQTS Spectrum of pathogenic mutations and associated polymorphisms in a cohort of 44 unrelated patients with long QT syndrome. Clin Genet. 2006 70(3):214-27. 16922724
Inherited 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
Other Cardiac Phenotype KCNE2 modulation of Kv4.3 current and its potential role in fatal rhythm disorders. Heart Rhythm. 2010 7(2):199-205. 20042375
Other Cardiac Phenotype High prevalence of genetic variants previously associated with LQT syndrome in new exome data. Eur J Hum Genet. 2012 20(8):905-8. doi: 10.1038/ejhg.2012.23. 22378279
Other Cardiac Phenotype Actionable, pathogenic incidental findings in 1,000 participants' exomes. Am J Hum Genet. 2013 93(4):631-40. doi: 10.1016/j.ajhg.2013.08.006. 24055113
Inherited ArrhythmiaAF Very early-onset lone atrial fibrillation patients have a high prevalence of rare variants in genes previously associated with atrial fibrillation. Heart Rhythm. 2014 11(2):246-51. doi: 10.1016/j.hrthm.2013.10.034. 24144883
Other Cardiac Phenotype Gain-of-function mutations in potassium channel subunit KCNE2 associated with early-onset lone atrial fibrillation. Biomark Med. 2014 8(4):557-70. doi: 10.2217/bmm.13.137. 24796621
Unknown Actionable exomic incidental findings in 6503 participants: challenges of variant classification. Genome Res. 2015 25(3):305-15. doi: 10.1101/gr.183483.114. 25637381
Other Cardiac Phenotype Rare genetic variants previously associated with congenital forms of long QT syndrome have little or no effect on the QT interval. Eur Heart J. 2015 36(37):2523-9. doi: 10.1093/eurheartj/ehv297. 26159999
Unknown Novel genotype-phenotype associations demonstrated by high-throughput sequencing in patients with hypertrophic cardiomyopathy. Heart. 2015 101(4):294-301. doi: 10.1136/heartjnl-2014-306387. 25351510
p.I57Mc.171T>G Putative BenignSIFT: deleterious
Polyphen: benign