| Paralogue | Variant | Associated Disease | Mapping Quality | Consensus | Pubmed |
|---|---|---|---|---|---|
| HCN4 | G482R | Bradycardia & left ventricular noncompaction cardi | High | 8 | 25145517, 25145517, 25145518, 25145518 |
| HCN4 | G482R | Sinus bradycardia & myocardial noncompaction | High | 8 | 26206080 |
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 | ----LGGPSIKDKYVTALYFTFSSLTSVGF>G<NVSPNTNSEKIFSICVMLIGSLMYASIFGN | 658 |
| KCNH1 | GK-WEGGPSKNSVYISSLYFTMTSLTSVGF>G<NIAPSTDIEKIFAVAIMMIGSLLYATIFGN | 497 |
| KCNH3 | GLELLGGPSLRSAYITSLYFALSSLTSVGF>G<NVSANTDTEKIFSICTMLIGALMHAVVFGN | 499 |
| KCNH4 | ---SVGGPSRRSAYIAALYFTLSSLTSVGF>G<NVCANTDAEKIFSICTMLIGALMHAVVFGN | 473 |
| KCNH5 | GI-WEGGPSKDSLYVSSLYFTMTSLTTIGF>G<NIAPTTDVEKMFSVAMMMVGSLLYATIFGN | 466 |
| KCNH6 | ----ASGPSVQDKYVTALYFTFSSLTSVGF>G<NVSPNTNSEKVFSICVMLIGSLMYASIFGN | 510 |
| KCNH7 | ----SSGPSIKDKYVTALYFTFSSLTSVGF>G<NVSPNTNSEKIFSICVMLIGSLMYASIFGN | 661 |
| KCNH8 | ---TLGGPSIRSAYIAALYFTLSSLTSVGF>G<NVSANTDAEKIFSICTMLIGALMHALVFGN | 468 |
| CNGA1 | -----EFGRLARKYVYSLYWSTLTLTTIG->E<TPPPVRDSEYVFVVVDFLIGVLIFATIVGN | 395 |
| CNGA2 | -----EYGYLAREYIYCLYWSTLTLTTIG->E<TPPPVKDEEYLFVIFDFLIGVLIFATIVGN | 370 |
| CNGA3 | -----EHGRLSRKYIYSLYWSTLTLTTIG->E<TPPPVKDEEYLFVVVDFLVGVLIFATIVGN | 398 |
| CNGA4 | -----GFERLRRQYLYSFYFSTLILTTVG->D<TPPPAREEEYLFMVGDFLLAVMGFATIMGS | 264 |
| CNGB1 | --------GVGNSYIRCYYFAVKTLITIG->G<LPDPKTLFEIVFQLLNYFTGVFAFSVMIGQ | 878 |
| CNGB3 | --------GEGNEYLRCYYWAVRTLITIG->G<LPEPQTLFEIVFQLLNFFSGVFVFSSLIGQ | 440 |
| HCN1 | -----VNDSWGKQYSYALFKAMSHMLCIGY>G<AQAPVSMSDLWITMLSMIVGATCYAMFVGH | 392 |
| HCN2 | -----VNHSWSELYSFALFKAMSHMLCIGY>G<RQAPESMTDIWLTMLSMIVGATCYAMFIGH | 461 |
| HCN3 | -----VNHSWGRQYSHALFKAMSHMLCIGY>G<QQAPVGMPDVWLTMLSMIVGATCYAMFIGH | 345 |
| HCN4 | -----VNNSWGKQYSYALFKAMSHMLCIGY>G<RQAPVGMSDVWLTMLSMIVGATCYAMFIGH | 512 |
| cons | > < |
| Protein | CDS | Disease Classification | Disease | dbSNP links | Effect Prediction |
|---|---|---|---|---|---|
| p.G628A | c.1883G>C | Inherited Arrhythmia | LQTS | rs199472955 | SIFT: deleterious Polyphen: probably damaging |
| Reports | Inherited Arrhythmia | LQTS | Clinical characteristics and genetic background of congenital long-QT syndrome diagnosed in fetal, neonatal, and infantile life: a nationwide questionnaire survey in Japan. Circ Arrhythm Electrophysiol. 2010 3(1):10-7. 19996378 | ||
| p.G628S | c.1882G>A | Inherited Arrhythmia | LQTS | rs121912507 | 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 | Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2. Circulation. 2000 102(10):1178-85. 10973849 | |||
| 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 | Long QT syndrome in neonates: conduction disorders associated with HERG mutations and sinus bradycardia with KCNQ1 mutations. J Am Coll Cardiol. 2004 43(5):826-30. 14998624 | ||||
| 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 | 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 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 | Mechanisms of cardiac arrhythmias and sudden death in transgenic rabbits with long QT syndrome. J Clin Invest. 2008 118(6):2246-59. 18464931 | |||
| 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 | Pore mutants of HERG and KvLQT1 downregulate the reciprocal currents in stable cell lines. Am J Physiol Heart Circ Physiol. 2010 299(5):H1525-34. 20833965 | |||
| Inherited Arrhythmia | LQTS | Blockade of permeation by potassium but normal gating of the G628S nonconducting hERG channel mutant. Biophys J. 2011 101(3):662-70. 21806934 | |||
| Inherited Arrhythmia | LQTS | HERG channel dysfunction in human long QT syndrome. Intracellular transport and functional defects. J Biol Chem. 1998 273(33):21061-6. 9694858 | |||
| Inherited Arrhythmia | LQTS | Isoform-specific dominant-negative effects associated with hERG1 G628S mutation in long QT syndrome. PLoS One. 2012 7(8):e42552. 22876326 | |||
| Inherited Arrhythmia | LQTS | Targeted modification of atrial electrophysiology by homogeneous transmural atrial gene transfer. Circulation. 2005 111(3):264-70. 15642761 | |||
| 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 | |||
| p.G628V | c.1883G>T | Inherited Arrhythmia | LQTS | rs199472955 | SIFT: deleterious Polyphen: probably damaging |
| Reports | 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 | 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.G628R | c.1882G>C | Inherited Arrhythmia | LQTS | SIFT: Polyphen: | |
| Reports | Inherited Arrhythmia | LQTS | Genetic characteristics of children and adolescents with long-QT syndrome diagnosed by school-based electrocardiographic screening programs. Circ Arrhythm Electrophysiol. 2014 7(1):107-12. doi: 10.1161/CIRCEP.113.000426. 24363352 | ||
| p.G628D | c.1883G>A | Inherited Arrhythmia | LQTS | SIFT: Polyphen: | |
| Reports | Inherited Arrhythmia | LQTS | Cardiac channelopathies associated with infantile fatal ventricular arrhythmias: from the cradle to the bench. J Cardiovasc Electrophysiol. 2014 25(1):66-73. doi: 10.1111/jce.12270. 24112685 | ||