| Paralogue | Variant | Associated Disease | Mapping Quality | Consensus | Pubmed |
|---|---|---|---|---|---|
| CNGA3 | T369S | Colour-blindness, total | Medium | 9 | 11536077 |
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 | ---LGGPSIKDKYVTALYFTFSSLTSVGFG>N<VSPNTNSEKIFSICVMLIGSLMYASIFGNV | 659 |
| KCNH1 | K-WEGGPSKNSVYISSLYFTMTSLTSVGFG>N<IAPSTDIEKIFAVAIMMIGSLLYATIFGNV | 498 |
| KCNH3 | LELLGGPSLRSAYITSLYFALSSLTSVGFG>N<VSANTDTEKIFSICTMLIGALMHAVVFGNV | 500 |
| KCNH4 | --SVGGPSRRSAYIAALYFTLSSLTSVGFG>N<VCANTDAEKIFSICTMLIGALMHAVVFGNV | 474 |
| KCNH5 | I-WEGGPSKDSLYVSSLYFTMTSLTTIGFG>N<IAPTTDVEKMFSVAMMMVGSLLYATIFGNV | 467 |
| KCNH6 | ---ASGPSVQDKYVTALYFTFSSLTSVGFG>N<VSPNTNSEKVFSICVMLIGSLMYASIFGNV | 511 |
| KCNH7 | ---SSGPSIKDKYVTALYFTFSSLTSVGFG>N<VSPNTNSEKIFSICVMLIGSLMYASIFGNV | 662 |
| KCNH8 | --TLGGPSIRSAYIAALYFTLSSLTSVGFG>N<VSANTDAEKIFSICTMLIGALMHALVFGNV | 469 |
| CNGA1 | ----EFGRLARKYVYSLYWSTLTLTTIG-E>T<PPPVRDSEYVFVVVDFLIGVLIFATIVGNI | 396 |
| CNGA2 | ----EYGYLAREYIYCLYWSTLTLTTIG-E>T<PPPVKDEEYLFVIFDFLIGVLIFATIVGNV | 371 |
| CNGA3 | ----EHGRLSRKYIYSLYWSTLTLTTIG-E>T<PPPVKDEEYLFVVVDFLVGVLIFATIVGNV | 399 |
| CNGA4 | ----GFERLRRQYLYSFYFSTLILTTVG-D>T<PPPAREEEYLFMVGDFLLAVMGFATIMGSM | 265 |
| CNGB1 | -------GVGNSYIRCYYFAVKTLITIG-G>L<PDPKTLFEIVFQLLNYFTGVFAFSVMIGQM | 879 |
| CNGB3 | -------GEGNEYLRCYYWAVRTLITIG-G>L<PEPQTLFEIVFQLLNFFSGVFVFSSLIGQM | 441 |
| HCN1 | ----VNDSWGKQYSYALFKAMSHMLCIGYG>A<QAPVSMSDLWITMLSMIVGATCYAMFVGHA | 393 |
| HCN2 | ----VNHSWSELYSFALFKAMSHMLCIGYG>R<QAPESMTDIWLTMLSMIVGATCYAMFIGHA | 462 |
| HCN3 | ----VNHSWGRQYSHALFKAMSHMLCIGYG>Q<QAPVGMPDVWLTMLSMIVGATCYAMFIGHA | 346 |
| HCN4 | ----VNNSWGKQYSYALFKAMSHMLCIGYG>R<QAPVGMSDVWLTMLSMIVGATCYAMFIGHA | 513 |
| cons | > < |
| Protein | CDS | Disease Classification | Disease | dbSNP links | Effect Prediction |
|---|---|---|---|---|---|
| p.N629D | c.1885A>G | Inherited Arrhythmia | LQTS | rs199472956 | SIFT: deleterious Polyphen: probably damaging |
| Reports | Inherited Arrhythmia | LQTS | Multiple different missense mutations in the pore region of HERG in patients with long QT syndrome. Hum Genet. 1998 102(3):265-72. 9544837 | ||
| Inherited Arrhythmia | LQTS | Characterization of a novel missense mutation in the pore of HERG in a patient with long QT syndrome. J Cardiovasc Electrophysiol. 1999 10(9):1262-70. 10517660 | |||
| Inherited Arrhythmia | LQTS | Novel gain-of-function mechanism in K(+) channel-related long-QT syndrome: altered gating and selectivity in the HERG1 N629D mutant. Circ Res. 2000 86(5):507-13. 10720411 | |||
| 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 | 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 | Role of mutation and pharmacologic block of human KCNH2 in vasculogenesis and fetal mortality: partial rescue by transforming growth factor-β. Circ Arrhythm Electrophysiol. 2015 8(2):420-8. doi: 10.1161/CIRCEP.114.001837. 25648353 | |||
| p.N629I | c.1886A>T | Inherited Arrhythmia | LQTS | rs199472957 | SIFT: deleterious Polyphen: probably damaging |
| Reports | 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 | 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 | 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.N629K | c.1887C>A | Inherited Arrhythmia | LQTS | rs41307295 | SIFT: deleterious Polyphen: probably damaging |
| Reports | Inherited Arrhythmia | LQTS | Characterization of a novel missense mutation in the pore of HERG in a patient with long QT syndrome. J Cardiovasc Electrophysiol. 1999 10(9):1262-70. 10517660 | ||
| 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.N629S | c.1886A>G | Inherited Arrhythmia | LQTS | rs199472957 | SIFT: deleterious Polyphen: probably damaging |
| Reports | Inherited Arrhythmia | LQTS | Multiple different missense mutations in the pore region of HERG in patients with long QT syndrome. Hum Genet. 1998 102(3):265-72. 9544837 | ||
| 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 | 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 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 | |||
| p.N629T | c.1886A>C | Inherited Arrhythmia | LQTS | rs199472957 | SIFT: deleterious Polyphen: probably damaging |
| Reports | Inherited Arrhythmia | LQTS | Long QT and Brugada syndrome gene mutations in New Zealand. Heart Rhythm. 2007 4(10):1306-14. 17905336 | ||
| p.N629K | c.1887C>G | Putative Benign | rs41307295 | SIFT: deleterious Polyphen: probably damaging | |