Paralogue | Variant | Associated Disease | Mapping Quality | Consensus | Pubmed |
---|---|---|---|---|---|
KCNQ2 | L243F | Epilepsy, benign neonatal | High | 9 | 14534157 |
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 KCNQ1.
KCNQ1 | RQGGTWRLLGSVVFIHRQELITTLYIGFLG>L<IFSSYFVYLAEKDAVN-----ESGRVEFGS | 298 |
KCNQ2 | RRGGTWKLLGSVVYAHSKELVTAWYIGFLC>L<ILASFLVYLAEKGE----------NDHFDT | 263 |
KCNQ3 | RRGGTWKLLGSAICAHSKELITAWYIGFLT>L<ILSSFLVYLVEKDVPEVDAQGEEMKEEFET | 302 |
KCNQ4 | RRGGTWKLLGSVVYAHSKELITAWYIGFLV>L<IFASFLVYLAEKDA----------NSDFSS | 269 |
KCNQ5 | RRGGTWKLLGSVVYAHSKELITAWYIGFLV>L<IFSSFLVYLVEKDA----------NKEFST | 297 |
KCNA1 | RHSKGLQILGQTLKASMRELGLLIFFLFIG>V<ILFSSAVYFAEAEE---------AESHFSS | 358 |
KCNA10 | RHSKGLQILGQTLKASMRELGLLIFFLFIG>V<ILFSSAVYFAEVDE---------PESHFSS | 407 |
KCNA2 | RHSKGLQILGQTLKASMRELGLLIFFLFIG>V<ILFSSAVYFAEADE---------RESQFPS | 360 |
KCNA3 | RHSKGLQILGQTLKASMRELGLLIFFLFIG>V<ILFSSAVYFAEADD---------PTSGFSS | 430 |
KCNA4 | RHSKGLQILGHTLRASMRELGLLIFFLFIG>V<ILFSSAVYFAEADE---------PTTHFQS | 510 |
KCNA5 | RHSKGLQILGKTLQASMRELGLLIFFLFIG>V<ILFSSAVYFAEADN---------QGTHFSS | 466 |
KCNA6 | RHSKGLQILGKTLQASMRELGLLIFFLFIG>V<ILFSSAVYFAEADD---------DDSLFPS | 408 |
KCNA7 | RHSKGLQILGQTLRASMRELGLLIFFLFIG>V<VLFSSAVYFAEVDR---------VDSHFTS | 344 |
KCNB1 | RHSTGLQSLGFTLRRSYNELGLLILFLAMG>I<MIFSSLVFFAEKDE---------DDTKFKS | 363 |
KCNB2 | RHSTGLQSLGFTLRRSYNELGLLILFLAMG>I<MIFSSLVFFAEKDE---------DATKFTS | 367 |
KCNC1 | RHFVGLRVLGHTLRASTNEFLLLIIFLALG>V<LIFATMIYYAERIGAQPNDPSASEHTHFKN | 386 |
KCNC2 | RHFVGLRVLGHTLRASTNEFLLLIIFLALG>V<LIFATMIYYAERVGAQPNDPSASEHTQFKN | 423 |
KCNC3 | RHFVGLRVLGHTLRASTNEFLLLIIFLALG>V<LIFATMIYYAERIGADPDDILGSNHTYFKN | 489 |
KCNC4 | RHFVGLRVLGHTLRASTNEFLLLIIFLALG>V<LIFATMIYYAERIGARPSDPRGNDHTDFKN | 422 |
KCND1 | RHSQGLRILGYTLKSCASELGFLLFSLTMA>I<IIFATVMFYAEKGT---------NKTNFTS | 358 |
KCND2 | RHSQGLRILGYTLKSCASELGFLLFSLTMA>I<IIFATVMFYAEKGS---------SASKFTS | 356 |
KCND3 | RHSQGLRILGYTLKSCASELGFLLFSLTMA>I<IIFATVMFYAEKGS---------SASKFTS | 353 |
KCNF1 | RHSSGLQTLTYALKRSFKELGLLLMYLAVG>I<FVFSALGYTMEQSH---------PETLFKS | 356 |
KCNG1 | RHSLGLQTLGLTARRCTREFGLLLLFLCVA>I<ALFAPLLYVIENEM-----A---DSPEFTS | 410 |
KCNG2 | RHSLGLRSLGLTMRRCAREFGLLLLFLCVA>M<ALFAPLVHLAEREL-----G---ARRDFSS | 355 |
KCNG3 | RHFIGLQTLGLTLKRCYREMVMLLVFICVA>M<AIFSALSQLLEHGL-----DLETSNKDFTS | 359 |
KCNG4 | RHSLGLQTLGLTVRRCTREFGLLLLFLAVA>I<TLFSPLVYVAEKES-----G---RVLEFTS | 404 |
KCNS1 | RHSTGLRSLGATLKHSYREVGILLLYLAVG>V<SVFSGVAYTAEKEE----------DVGFNT | 407 |
KCNS2 | RHSTGLRSLGATLKYSYKEVGLLLLYLSVG>I<SIFSVVAYTIEKEE----------NEGLAT | 360 |
KCNS3 | RHSVGLRSLGATLRHSYHEVGLLLLFLSVG>I<SIFSVLIYSVEKDD---------HTSSLTS | 356 |
KCNV1 | RHSTGLRSLGMTITQCYEEVGLLLLFLSVG>I<SIFSTVEYFAEQSI---------PDTTFTS | 378 |
KCNV2 | RHSTGLRAFGFTLRQCYQQVGCLLLFIAMG>I<FTFSAAVYSVEHDV---------PSTNFTT | 443 |
cons | > < |
Protein | CDS | Disease Classification | Disease | dbSNP links | Effect Prediction |
---|---|---|---|---|---|
p.L273F | c.817C>T | Inherited Arrhythmia | LQTS,JLNS | rs120074180 | SIFT: deleterious Polyphen: probably damaging |
Reports | Inherited Arrhythmia | LQTS | Positional cloning of a novel potassium channel gene: KVLQT1 mutations cause cardiac arrhythmias. Nat Genet. 1996 12(1):17-23. 8528244 | ||
Inherited Arrhythmia | LQTS | Dominant-negative KvLQT1 mutations underlie the LQT1 form of long QT syndrome. Circulation. 1997 96(6):1733-6. 9323054 | |||
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 | A founder mutation of the potassium channel KCNQ1 in long QT syndrome: implications for estimation of disease prevalence and molecular diagnostics. J Am Coll Cardiol. 2001 37(2):562-8. 11216980 | |||
Inherited Arrhythmia | LQTS | Location of mutation in the KCNQ1 and phenotypic presentation of long QT syndrome. J Cardiovasc Electrophysiol. 2003 14(11):1149-53. 14678125 | |||
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 | 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 | |||
Inherited Arrhythmia | LQTS | Classification of the long-QT syndrome based on discriminant analysis of T-wave morphology. Med Biol Eng Comput. 2006 44(7):543-9. 16937190 | |||
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 | Clinical aspects of type-1 long-QT syndrome by location, coding type, and biophysical function of mutations involving the KCNQ1 gene. Circulation. 2007 115(19):2481-9. 17470695 | |||
Inherited Arrhythmia | LQTS | Abnormal KCNQ1 trafficking influences disease pathogenesis in hereditary long QT syndromes (LQT1). Cardiovasc Res. 2005 67(3):476-86. 15935335 | |||
Inherited Arrhythmia | LQTS | Identification of specific pore residues mediating KCNQ1 inactivation. A novel mechanism for long QT syndrome. J Biol Chem. 2001 276(17):13600-5. 11278406 | |||
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 | JLNS | Genotype-phenotype analysis of Jervell and Lange-Nielsen syndrome in six families from Saudi Arabia. Clin Genet. 2015 87(1):74-9. doi: 10.1111/cge.12330. 24372464 | |||
Inherited Arrhythmia | LQTS | Further evidence of the association between LQT syndrome and epilepsy in a family with KCNQ1 pathogenic variant. Seizure. 2015 25:65-7. doi: 10.1016/j.seizure.2015.01.003. 25645639 | |||
p.L273R | c.818T>G | Inherited Arrhythmia | LQTS | rs199472727 | SIFT: deleterious Polyphen: probably damaging |
Reports | 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 | 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 |