| Paralogue | Variant | Associated Disease | Mapping Quality | Consensus | Pubmed |
|---|---|---|---|---|---|
| CNGA3 | R283W | Colour-blindness, total | High | 6 | 9662398, 20238023, 24504161, 26992781 |
| CNGA3 | R283Q | Colour-blindness, total | High | 6 | 9662398, 25616768 |
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 | -------------------LIGLLKTARLL>R<LVRVARKLDRY-----SEYGAAV-LFLLMC | 555 |
| KCNH1 | Q---IPPPLEGRESQGISSLFSSLKVVRLL>R<LGRVARKLDHY-----IEYGAAV-LVLLVC | 384 |
| KCNH3 | V---Y-------------FGAHLLKTVRLL>R<LLRLLPRLDRY-----SQYSAVV-LTLLMA | 365 |
| KCNH4 | V---T-------------SLVHLLKTVRLL>R<LLRLLQKLERY-----SQCSAVV-LTLLMS | 367 |
| KCNH5 | ----------------ISSLFSSLKVVRLL>R<LGRVARKLDHY-----LEYGAAV-LVLLVC | 354 |
| KCNH6 | T---T-------------TLIGLLKTARLL>R<LVRVARKLDRY-----SEYGAAV-LFLLMC | 406 |
| KCNH7 | T---T-------------TLIGLLKTARLL>R<LVRVARKLDRY-----SEYGAAV-LMLLMC | 557 |
| KCNH8 | V---V-------------SLVHLLKTVRLL>R<LLRLLQKLDRY-----SQHSTIV-LTLLMS | 361 |
| CNGA1 | ------------------PEIRLNRLLRFS>R<MFEFFQRTETR-----TNYPNIFRISNLVM | 305 |
| CNGA2 | ------------------PEVRFNRLLHFA>R<MFEFFDRTETR-----TNYPNIFRISNLVL | 280 |
| CNGA3 | ------------------PEVRFNRLLKFS>R<LFEFFDRTETR-----TNYPNMFRIGNLVL | 308 |
| CNGA4 | ------------------PTLRLNRFLRAP>R<LFEAFDRTETR-----TAYPNAFRIAKLML | 174 |
| CNGB1 | ------------------PLLRLPRCLKYM>A<FFEFNSRLESI-----LSKAYVYRVIRTTA | 796 |
| CNGB3 | ------------------PMFRANRMLKYT>S<FFEFNHHLESI-----MDKAYIYRVIRTTG | 358 |
| HCN1 | IVRFT-------------KILSLLRLLRLS>R<LIRYIHQWEEIFHMTYDLASAVVRIFNLIG | 303 |
| HCN2 | IVRFT-------------KILSLLRLLRLS>R<LIRYIHQWEEIFHMTYDLASAVMRICNLIS | 372 |
| HCN3 | IVRFT-------------KILSLLRLLRLS>R<LIRYIHQWEEIFHMTYDLASAVVRIFNLIG | 256 |
| HCN4 | IVRFT-------------KILSLLRLLRLS>R<LIRYIHQWEEIFHMTYDLASAVVRIVNLIG | 423 |
| cons | > < |
| Protein | CDS | Disease Classification | Disease | dbSNP links | Effect Prediction |
|---|---|---|---|---|---|
| p.R531Q | c.1592G>A | Inherited Arrhythmia | LQTS | rs199473515 | SIFT: deleterious Polyphen: probably damaging |
| Reports | 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 | Mechanistic basis for type 2 long QT syndrome caused by KCNH2 mutations that disrupt conserved arginine residues in the voltage sensor. J Membr Biol. 2013 246(5):355-64. doi: 10.1007/s00232-013-9539-6. 23546015 | |||
| p.R531W | c.1591C>T | Inherited Arrhythmia | LQTS | rs199472915 | 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 | Mechanistic basis for type 2 long QT syndrome caused by KCNH2 mutations that disrupt conserved arginine residues in the voltage sensor. J Membr Biol. 2013 246(5):355-64. doi: 10.1007/s00232-013-9539-6. 23546015 | |||