No paralogue variants have been mapped to residue 561 for KCNH2.
| KCNH2 | RKLDRY-----SEYGAAV-LFLLMCTFALI>A<HWLACIWYAIGNMEQPHMDSR----IGWLH | 587 |
| KCNH1 | RKLDHY-----IEYGAAV-LVLLVCVFGLA>A<HWMACIWYSIGDYEIFDEDTKTIRNNSWLY | 420 |
| KCNH3 | PRLDRY-----SQYSAVV-LTLLMAVFALL>A<HWVACVWFYIGQREIESSESELPE-IGWLQ | 400 |
| KCNH4 | QKLERY-----SQCSAVV-LTLLMSVFALL>A<HWMACIWYVIGRREMEANDPLLWD-IGWLH | 402 |
| KCNH5 | RKLDHY-----LEYGAAV-LVLLVCVFGLV>A<HWLACIWYSIGDYEVIDEVTNTIQIDSWLY | 390 |
| KCNH6 | RKLDRY-----SEYGAAV-LFLLMCTFALI>A<HWLACIWYAIGNVERPYLEHK----IGWLD | 438 |
| KCNH7 | RKLDRY-----SEYGAAV-LMLLMCIFALI>A<HWLACIWYAIGNVERPYLTDK----IGWLD | 589 |
| KCNH8 | QKLDRY-----SQHSTIV-LTLLMSMFALL>A<HWMACIWYVIGKMEREDNSLLKWE-VGWLH | 396 |
| CNGA1 | QRTETR-----TNYPNIFRISNLVMYIVII>I<HWNACVFYSISKAIGFGND-------TWVY | 334 |
| CNGA2 | DRTETR-----TNYPNIFRISNLVLYILVI>I<HWNACIYYAISKSIGFGVD-------TWVY | 309 |
| CNGA3 | DRTETR-----TNYPNMFRIGNLVLYILII>I<HWNACIYFAISKFIGFGTD-------SWVY | 337 |
| CNGA4 | DRTETR-----TAYPNAFRIAKLMLYIFVV>I<HWNSCLYFALSRYLGFGRD-------AWVY | 203 |
| CNGB1 | SRLESI-----LSKAYVYRVIRTTAYLLYS>L<HLNSCLYYWASAYQGLGST-------HWVY | 825 |
| CNGB3 | HHLESI-----MDKAYIYRVIRTTGYLLFI>L<HINACVYYWASNYEGIGTT-------RWVY | 387 |
| HCN1 | HQWEEIFHMTYDLASAVVRIFNLIGMMLLL>C<HWDGCLQFLVPLLQDFPPD-------CWVS | 332 |
| HCN2 | HQWEEIFHMTYDLASAVMRICNLISMMLLL>C<HWDGCLQFLVPMLQDFPRN-------CWVS | 401 |
| HCN3 | HQWEEIFHMTYDLASAVVRIFNLIGMMLLL>C<HWDGCLQFLVPMLQDFPPD-------CWVS | 285 |
| HCN4 | HQWEEIFHMTYDLASAVVRIVNLIGMMLLL>C<HWDGCLQFLVPMLQDFPDD-------CWVS | 452 |
| cons | > < |
| Protein | CDS | Disease Classification | Disease | dbSNP links | Effect Prediction |
|---|---|---|---|---|---|
| p.A561P | c.1681G>C | Inherited Arrhythmia | LQTS | rs199472921 | SIFT: deleterious Polyphen: probably damaging |
| Reports | Inherited Arrhythmia | LQTS | A common antitussive drug, clobutinol, precipitates the long QT syndrome 2. Mol Pharmacol. 2004 66(5):1093-102. 15280442 | ||
| Inherited Arrhythmia | LQTS | Mutation in the KCNQ1 gene leading to the short QT-interval syndrome. Circulation. 2004 109(20):2394-7. 15159330 | |||
| Inherited Arrhythmia | LQTS | 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.A561T | c.1681G>A | Inherited Arrhythmia | LQTS | rs199472921 | SIFT: deleterious Polyphen: probably damaging |
| Reports | Inherited Arrhythmia | LQTS | A mutation in HERG associated with notched T waves in long QT syndrome. J Mol Cell Cardiol. 1996 28(8):1609-15. 8877771 | ||
| Inherited Arrhythmia | LQTS | Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2. Circulation. 2000 102(10):1178-85. 10973849 | |||
| Inherited Arrhythmia | LQTS | Notched T waves on Holter recordings enhance detection of patients with LQt2 (HERG) mutations. Circulation. 2001 103(8):1095-101. 11222472 | |||
| Inherited Arrhythmia | LQTS | Increased risk of arrhythmic events in long-QT syndrome with mutations in the pore region of the human ether-a-go-go-related gene potassium channel. Circulation. 2002 105(7):794-9. 11854117 | |||
| Other Cardiac Phenotype | Postmortem molecular screening in unexplained sudden death. J Am Coll Cardiol. 2004 43(9):1625-9. 15120823 | ||||
| Inherited Arrhythmia | LQTS | 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 Arrhythmia | LQTS | Gene sequencing in neonates and infants with the long QT syndrome. Genet Test. 2005 9(4):281-4. 16379539 | |||
| Inherited Arrhythmia | LQTS | Most LQT2 mutations reduce Kv11.1 (hERG) current by a class 2 (trafficking-deficient) mechanism. Circulation. 2006 113(3):365-73. 16432067 | |||
| Inherited Arrhythmia | LQTS | Mutation site dependent variability of cardiac events in Japanese LQT2 form of congenital long-QT syndrome. Circ J. 2008 72(5):694-9. 18441445 | |||
| Inherited Arrhythmia | LQTS | 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 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 | Allele-specific RNA interference rescues the long-QT syndrome phenotype in human-induced pluripotency stem cell cardiomyocytes. Eur Heart J. 2014 35(16):1078-87. doi: 10.1093/eurheartj/eht067. 23470493 | |||
| p.A561V | c.1682C>T | Inherited Arrhythmia | LQTS | rs121912504 | SIFT: deleterious Polyphen: probably damaging |
| Reports | Inherited Arrhythmia | LQTS | A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome. Cell. 1995 80(5):795-803. 7889573 | ||
| Inherited Arrhythmia | LQTS | Low penetrance in the long-QT syndrome: clinical impact. Circulation. 1999 99(4):529-33. 9927399 | |||
| Inherited Arrhythmia | LQTS | Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2. Circulation. 2000 102(10):1178-85. 10973849 | |||
| Inherited Arrhythmia | LQTS | Retention in the endoplasmic reticulum as a mechanism of dominant-negative current suppression in human long QT syndrome. J Mol Cell Cardiol. 2000 32(12):2327-37. 11113008 | |||
| Inherited Arrhythmia | LQTS | Screening for mutations and polymorphisms in the genes KCNH2 and KCNE2 encoding the cardiac HERG/MiRP1 ion channel: implications for acquired and congenital long Q-T syndrome. Clin Chem. 2001 47(8):1390-5. 11468227 | |||
| Inherited Arrhythmia | LQTS | Automated mutation screening using dideoxy fingerprinting and capillary array electrophoresis. Hum Mutat. 2001 18(5):451-7. 11668638 | |||
| Inherited Arrhythmia | LQTS | Increased risk of arrhythmic events in long-QT syndrome with mutations in the pore region of the human ether-a-go-go-related gene potassium channel. Circulation. 2002 105(7):794-9. 11854117 | |||
| Inherited Arrhythmia | LQTS | Compound mutations: a common cause of severe long-QT syndrome. Circulation. 2004 109(15):1834-41. 15051636 | |||
| Inherited Arrhythmia | LQTS | 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 Arrhythmia | LQTS | Most LQT2 mutations reduce Kv11.1 (hERG) current by a class 2 (trafficking-deficient) mechanism. Circulation. 2006 113(3):365-73. 16432067 | |||
| Inherited Arrhythmia | LQTS | [Construction of eukaryotic expression vector of congenital long QT syndrome related HERG gene A561V mutation and its expression in HEK293 cells]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2006 23(6):627-30. 17160940 | |||
| Inherited Arrhythmia | LQTS | [Functional expression of congenital long QT syndrome related HERG mutation A561V in vitro]. Zhonghua Xin Xue Guan Bing Za Zhi. 2007 35(2):143-6. 17445409 | |||
| Inherited Arrhythmia | LQTS | Mutation site dependent variability of cardiac events in Japanese LQT2 form of congenital long-QT syndrome. Circ J. 2008 72(5):694-9. 18441445 | |||
| Inherited Arrhythmia | LQTS | Functional studies on three novel HCNH2 mutations in Taiwan: identification of distinct mechanisms of channel defect and dissociation between glycosylation defect and assembly defect. Biochem Biophys Res Commun. 2008 373(4):572-8. 18593567 | |||
| Inherited Arrhythmia | LQTS | 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 Arrhythmia | LQTS | Genetic testing for long-QT syndrome: distinguishing pathogenic mutations from benign variants. Circulation. 2009 120(18):1752-60. 19841300 | |||
| Inherited Arrhythmia | LQTS | Four novel KVLQT1 and four novel HERG mutations in familial long-QT syndrome. Circulation. 1997 95(3):565-7. 9024139 | |||
| Inherited Arrhythmia | LQTS | 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 | |||
| Unknown | The dominant negative LQT2 mutation A561V reduces wild-type HERG expression. J Biol Chem. 2000 275(15):11241-8. 10753933 | ||||
| Inherited Arrhythmia | LQTS | Re-trafficking of hERG reverses long QT syndrome 2 phenotype in human iPS-derived cardiomyocytes. Cardiovasc Res. 2014 102(3):497-506. doi: 10.1093/cvr/cvu060. 24623279 | |||
| Inherited Arrhythmia | LQTS | Association of the hERG mutation with long-QT syndrome type 2, syncope and epilepsy. Mol Med Rep. 2016 13(3):2467-75. doi: 10.3892/mmr.2016.4859. 26847485 | |||