| Paralogue | Variant | Associated Disease | Mapping Quality | Consensus | Pubmed |
|---|---|---|---|---|---|
| CNGA3 | S334F | Cone dystrophy | Medium | 8 | 24903488 |
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 | ALIAHWLACIWYAIGNMEQPHMDSR----I>G<WLHNLGDQIGKPYNSS----------G--- | 601 |
| KCNH1 | GLAAHWMACIWYSIGDYEIFDEDTKTIRNN>S<WLYQLAMDIGTPYQFN--------GSG--- | 436 |
| KCNH3 | ALLAHWVACVWFYIGQREIESSESELPE-I>G<WLQELARRLETPYYLVGRRPAGGNSSGQSD | 427 |
| KCNH4 | ALLAHWMACIWYVIGRREMEANDPLLWD-I>G<WLHELGKRLEVPYVNG-------------- | 415 |
| KCNH5 | GLVAHWLACIWYSIGDYEVIDEVTNTIQID>S<WLYQLALSIGTPYRYN--------T-S--- | 405 |
| KCNH6 | ALIAHWLACIWYAIGNVERPYLEHK----I>G<WLDSLGVQLGKRYNGS----------D--- | 452 |
| KCNH7 | ALIAHWLACIWYAIGNVERPYLTDK----I>G<WLDSLGQQIGKRYNDS----------D--- | 603 |
| KCNH8 | ALLAHWMACIWYVIGKMEREDNSLLKWE-V>G<WLHELGKRLESPYYGNN------------- | 410 |
| CNGA1 | VIIIHWNACVFYSISKAIGFGND------->T<WVYPD---INDP------------------ | 340 |
| CNGA2 | LVIIHWNACIYYAISKSIGFGVD------->T<WVYPN---ITDP------------------ | 315 |
| CNGA3 | LIIIHWNACIYFAISKFIGFGTD------->S<WVYPN---ISIP------------------ | 343 |
| CNGA4 | FVVIHWNSCLYFALSRYLGFGRD------->A<WVYPD---PAQP------------------ | 209 |
| CNGB1 | LYSLHLNSCLYYWASAYQGLGST------->H<WVYD-------------------------- | 826 |
| CNGB3 | LFILHINACVYYWASNYEGIGTT------->R<WVYD-------------------------- | 388 |
| HCN1 | LLLCHWDGCLQFLVPLLQDFPPD------->C<WVS-----LNEM------------------ | 336 |
| HCN2 | LLLCHWDGCLQFLVPMLQDFPRN------->C<WVS-----INGM------------------ | 405 |
| HCN3 | LLLCHWDGCLQFLVPMLQDFPPD------->C<WVS-----INHM------------------ | 289 |
| HCN4 | LLLCHWDGCLQFLVPMLQDFPDD------->C<WVS-----INNM------------------ | 456 |
| cons | > < |
| Protein | CDS | Disease Classification | Disease | dbSNP links | Effect Prediction |
|---|---|---|---|---|---|
| p.G584C | c.1750G>T | Inherited Arrhythmia | LQTS | rs199473428 | SIFT: deleterious Polyphen: probably damaging |
| Reports | 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 | ||
| p.G584R | c.1750G>C | Inherited Arrhythmia | LQTS | rs199473428 | 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 | ||
| p.G584S | c.1750G>A | Inherited Arrhythmia | LQTS | rs199473428 | SIFT: tolerated Polyphen: benign |
| 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 | |||
| 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 | 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 | Not all hERG pore domain mutations have a severe phenotype: G584S has an inactivation gating defect with mild phenotype compared to G572S, which has a dominant negative trafficking defect and a severe phenotype. J Cardiovasc Electrophysiol. 2009 20(8):923-30. 19490267 | |||
| 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 | |||
| Other Cardiac Phenotype | Utility and limitations of exome sequencing as a genetic diagnostic tool for conditions associated with pediatric sudden cardiac arrest/sudden cardiac death. Hum Genomics. 2015 9:15. doi: 10.1186/s40246-015-0038-y. 26187847 | ||||
| p.G584V | c.1751G>T | Inherited Arrhythmia | LQTS | rs199473429 | SIFT: deleterious Polyphen: probably damaging |
| Reports | Inherited Arrhythmia | LQTS | Molecular genetic analysis of long QT syndrome in Norway indicating a high prevalence of heterozygous mutation carriers. Scand J Clin Lab Invest. 2008 68(5):362-8. 18752142 | ||