| Paralogue | Variant | Associated Disease | Mapping Quality | Consensus | Pubmed |
|---|---|---|---|---|---|
| HCN4 | Y481H | Bradycardia & left ventricular noncompaction cardi | Medium | 7 | 25145517, 25145517 |
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 | -----LGGPSIKDKYVTALYFTFSSLTSVG>F<GNVSPNTNSEKIFSICVMLIGSLMYASIFG | 657 |
| KCNH1 | -GK-WEGGPSKNSVYISSLYFTMTSLTSVG>F<GNIAPSTDIEKIFAVAIMMIGSLLYATIFG | 496 |
| KCNH3 | TGLELLGGPSLRSAYITSLYFALSSLTSVG>F<GNVSANTDTEKIFSICTMLIGALMHAVVFG | 498 |
| KCNH4 | ----SVGGPSRRSAYIAALYFTLSSLTSVG>F<GNVCANTDAEKIFSICTMLIGALMHAVVFG | 472 |
| KCNH5 | -GI-WEGGPSKDSLYVSSLYFTMTSLTTIG>F<GNIAPTTDVEKMFSVAMMMVGSLLYATIFG | 465 |
| KCNH6 | -----ASGPSVQDKYVTALYFTFSSLTSVG>F<GNVSPNTNSEKVFSICVMLIGSLMYASIFG | 509 |
| KCNH7 | -----SSGPSIKDKYVTALYFTFSSLTSVG>F<GNVSPNTNSEKIFSICVMLIGSLMYASIFG | 660 |
| KCNH8 | ----TLGGPSIRSAYIAALYFTLSSLTSVG>F<GNVSANTDAEKIFSICTMLIGALMHALVFG | 467 |
| CNGA1 | ------EFGRLARKYVYSLYWSTLTLTTIG>-<ETPPPVRDSEYVFVVVDFLIGVLIFATIVG | 394 |
| CNGA2 | ------EYGYLAREYIYCLYWSTLTLTTIG>-<ETPPPVKDEEYLFVIFDFLIGVLIFATIVG | 369 |
| CNGA3 | ------EHGRLSRKYIYSLYWSTLTLTTIG>-<ETPPPVKDEEYLFVVVDFLVGVLIFATIVG | 397 |
| CNGA4 | ------GFERLRRQYLYSFYFSTLILTTVG>-<DTPPPAREEEYLFMVGDFLLAVMGFATIMG | 263 |
| CNGB1 | ---------GVGNSYIRCYYFAVKTLITIG>-<GLPDPKTLFEIVFQLLNYFTGVFAFSVMIG | 877 |
| CNGB3 | ---------GEGNEYLRCYYWAVRTLITIG>-<GLPEPQTLFEIVFQLLNFFSGVFVFSSLIG | 439 |
| HCN1 | ------VNDSWGKQYSYALFKAMSHMLCIG>Y<GAQAPVSMSDLWITMLSMIVGATCYAMFVG | 391 |
| HCN2 | ------VNHSWSELYSFALFKAMSHMLCIG>Y<GRQAPESMTDIWLTMLSMIVGATCYAMFIG | 460 |
| HCN3 | ------VNHSWGRQYSHALFKAMSHMLCIG>Y<GQQAPVGMPDVWLTMLSMIVGATCYAMFIG | 344 |
| HCN4 | ------VNNSWGKQYSYALFKAMSHMLCIG>Y<GRQAPVGMSDVWLTMLSMIVGATCYAMFIG | 511 |
| cons | > < |
| Protein | CDS | Disease Classification | Disease | dbSNP links | Effect Prediction |
|---|---|---|---|---|---|
| p.F627I | c.1879T>A | Inherited Arrhythmia | LQTS | rs199472954 | SIFT: deleterious Polyphen: probably damaging |
| Reports | Inherited Arrhythmia | LQTS | Role of HCN4 channel in preventing ventricular arrhythmia. J Hum Genet. 2009 54(2):115-21. 19165230 | ||
| p.F627L | c.1879T>C | Inherited Arrhythmia | LQTS | rs199472954 | SIFT: deleterious Polyphen: probably damaging |
| Reports | Inherited Arrhythmia | LQTS | In utero onset of long QT syndrome with atrioventricular block and spontaneous or lidocaine-induced ventricular tachycardia: compound effects of hERG pore region mutation and SCN5A N-terminus variant. Heart Rhythm. 2008 5(11):1567-74. 18848812 | ||
| 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.F627L | c.1881C>G | Inherited Arrhythmia | LQTS | rs199473039 | 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 | 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.F627L | c.1881C>A | Inherited Arrhythmia | LQTS | SIFT: Polyphen: | |
| Reports | Inherited Arrhythmia | LQTS | Post-mortem genetic testing in a family with long-QT syndrome and hypertrophic cardiomyopathy. Cardiovasc Pathol. 2014 23(2):107-9. doi: 10.1016/j.carpath.2013.11.003. 24322056 | ||
| 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 | |||