No paralogue variants have been mapped to residue 176 for KCNH2.
| KCNH2 | NHRGPPTSWLAPGRAKTFRLKLPALLALTA>R<ESSVRSGGAGGAGAPGAVVVDVDLTPAAPS | 206 |
| KCNH1 | --------------CKGWG----------->-<------------------------------ | 149 |
| KCNH3 | --------------WKETGGGRR------->-<------------------------------ | 153 |
| KCNH4 | --------------GRGDSNHEN------->-<------------------------------ | 154 |
| KCNH5 | --------------TKGWT----------->-<------------------------------ | 147 |
| KCNH6 | ---------LAKCSSRSLSQRLLSQSFLGS>E<GSHGRPGGPG-------------------- | 167 |
| KCNH7 | N----PILPIKTVNRKFFGFKFPGLRVLTY>R<KQSLPQEDPD------VVVIDS----SKHS | 191 |
| KCNH8 | -----------------DKKEDK------->-<------------------------------ | 149 |
| CNGA1 | ------------------------------>-<------------------------------ | |
| CNGA2 | ------------------------------>-<------------------------------ | |
| CNGA3 | ------------------------------>-<------------------------------ | |
| CNGA4 | ------------------------------>-<------------------------------ | |
| CNGB1 | QVGVGQSEEDGTRPQSTSDQKLWEEVGEEA>K<KEAEEKAKEEAEEVAEEEAEKEPQDWAETK | 444 |
| CNGB3 | ----SRRNEEGSHPSNQSQQ----TTAQEE>N<KGEEKSLKTKSTPVTSEEPHTNIQDKLSKK | 76 |
| HCN1 | --------------PAGG---F-------->-<------------------------------ | 81 |
| HCN2 | --------------EAGSEEAG-------->-<------------------------------ | 150 |
| HCN3 | ---------------------G-------->-<------------------------------ | 41 |
| HCN4 | ---------------AAGDQIL-------->-<------------------------------ | 201 |
| cons | > < |
| Protein | CDS | Disease Classification | Disease | dbSNP links | Effect Prediction |
|---|---|---|---|---|---|
| p.R176W | c.526C>T | Conflict | rs36210422 | SIFT: deleterious Polyphen: probably damaging | |
| Reports | Inherited Arrhythmia | LQTS | Sinus node function and ventricular repolarization during exercise stress test in long QT syndrome patients with KvLQT1 and HERG potassium channel defects. J Am Coll Cardiol. 1999 34(3):823-9. 10483966 | ||
| Inherited Arrhythmia | LQTS | Survey of the coding region of the HERG gene in long QT syndrome reveals six novel mutations and an amino acid polymorphism with possible phenotypic effects. Hum Mutat. 2000 15(6):580-1. 10862094 | |||
| Putative Benign | Ethnic differences in cardiac potassium channel variants: implications for genetic susceptibility to sudden cardiac death and genetic testing for congenital long QT syndrome. Mayo Clin Proc. 2003 78(12):1479-87. 14661677 | ||||
| Inherited Arrhythmia | LQTS | Allelic dropout in long QT syndrome genetic testing: a possible mechanism underlying false-negative results. Heart Rhythm. 2006 3(7):815-21. 16818214 | |||
| Other Cardiac Phenotype | Association of torsades de pointes with novel and known single nucleotide polymorphisms in long QT syndrome genes. Am Heart J. 2006 152(6):1116-22. 17161064 | ||||
| Inherited Arrhythmia | LQTS | High prevalence of four long QT syndrome founder mutations in the Finnish population. Ann Med. 2009 41(3):234-40. 19160088 | |||
| Benign | Genetic testing for long-QT syndrome: distinguishing pathogenic mutations from benign variants. Circulation. 2009 120(18):1752-60. 19841300 | ||||
| Inherited Arrhythmia | LQTS | The genetic basis of long QT and short QT syndromes: a mutation update. Hum Mutat. 2009 30(11):1486-511. 19862833 | |||
| Inherited Arrhythmia | LQTS | Molecular characterization of two founder mutations causing long QT syndrome and identification of compound heterozygous patients. Ann Med. 2006 38(4):294-304. 16754261 | |||
| Inherited Arrhythmia | LQTS | Model for long QT syndrome type 2 using human iPS cells demonstrates arrhythmogenic characteristics in cell culture. Dis Model Mech. 2012 5(2):220-30. doi: 10.1242/dmm.008409. 22052944 | |||
| Inherited Arrhythmia | LQTS | 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 | |||
| Putative Benign | 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 Arrhythmia | LQTS | 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 | |||
| Inherited Arrhythmia | LQTS | A presumably benign human ether-a-go-go-related gene mutation (R176W) with a malignant primary manifestation of long QT syndrome. Cardiol Young. 2012 22(3):360-3. doi: 10.1017/S1047951111001831. 22067087 | |||
| 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 | ||||