| Paralogue | Variant | Associated Disease | Mapping Quality | Consensus | Pubmed |
|---|---|---|---|---|---|
| KCNH5 | R327H | Epileptic encephalopathy | High | 6 | 23647072, 24133262 |
| CNGA1 | R277W | Retinitis pigmentosa, autosomal recessive | High | 6 | 24265693 |
| KCNH1 | R357Q | Intellectual disability | High | 6 | 26264464, 26818738 |
| KCNH1 | R357P | Hypotonia, seizures and developmental delay | High | 6 | 26818738 |
| CNGA1 | R277Q | Retinitis pigmentosa, autosomal recessive | High | 6 | 26806561 |
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 | ----------------------LIGLLKTA>R<LLRLVRVARKLDRY-----SEYGAAV-LFL | 552 |
| KCNH1 | FADQ---IPPPLEGRESQGISSLFSSLKVV>R<LLRLGRVARKLDHY-----IEYGAAV-LVL | 381 |
| KCNH3 | ---V---Y-------------FGAHLLKTV>R<LLRLLRLLPRLDRY-----SQYSAVV-LTL | 362 |
| KCNH4 | ---V---T-------------SLVHLLKTV>R<LLRLLRLLQKLERY-----SQCSAVV-LTL | 364 |
| KCNH5 | -------------------ISSLFSSLKVV>R<LLRLGRVARKLDHY-----LEYGAAV-LVL | 351 |
| KCNH6 | ---T---T-------------TLIGLLKTA>R<LLRLVRVARKLDRY-----SEYGAAV-LFL | 403 |
| KCNH7 | ---T---T-------------TLIGLLKTA>R<LLRLVRVARKLDRY-----SEYGAAV-LML | 554 |
| KCNH8 | ---V---V-------------SLVHLLKTV>R<LLRLLRLLQKLDRY-----SQHSTIV-LTL | 358 |
| CNGA1 | ---------------------PEIRLNRLL>R<FSRMFEFFQRTETR-----TNYPNIFRISN | 302 |
| CNGA2 | ---------------------PEVRFNRLL>H<FARMFEFFDRTETR-----TNYPNIFRISN | 277 |
| CNGA3 | ---------------------PEVRFNRLL>K<FSRLFEFFDRTETR-----TNYPNMFRIGN | 305 |
| CNGA4 | ---------------------PTLRLNRFL>R<APRLFEAFDRTETR-----TAYPNAFRIAK | 171 |
| CNGB1 | ---------------------PLLRLPRCL>K<YMAFFEFNSRLESI-----LSKAYVYRVIR | 793 |
| CNGB3 | ---------------------PMFRANRML>K<YTSFFEFNHHLESI-----MDKAYIYRVIR | 355 |
| HCN1 | LR-IVRFT-------------KILSLLRLL>R<LSRLIRYIHQWEEIFHMTYDLASAVVRIFN | 300 |
| HCN2 | LR-IVRFT-------------KILSLLRLL>R<LSRLIRYIHQWEEIFHMTYDLASAVMRICN | 369 |
| HCN3 | LR-IVRFT-------------KILSLLRLL>R<LSRLIRYIHQWEEIFHMTYDLASAVVRIFN | 253 |
| HCN4 | LR-IVRFT-------------KILSLLRLL>R<LSRLIRYIHQWEEIFHMTYDLASAVVRIVN | 420 |
| cons | > < |
| Protein | CDS | Disease Classification | Disease | dbSNP links | Effect Prediction |
|---|---|---|---|---|---|
| p.R528P | c.1583G>C | Inherited Arrhythmia | LQTS | rs199472914 | SIFT: deleterious Polyphen: probably damaging |
| Reports | 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 | ||
| p.R528W | c.1582C>T | Putative Benign | SIFT: deleterious Polyphen: probably damaging | ||
| p.Arg528Gln | c.1583G>A | Unknown | SIFT: Polyphen: | ||