Paralogue | Variant | Associated Disease | Mapping Quality | Consensus | Pubmed |
---|---|---|---|---|---|
KCNQ2 | N258S | Epilepsy, benign neonatal | Medium | 8 | 18246739, 21913284 |
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 | IGFLGLIFSSYFVYLAEKDAVN-----ESG>R<VEFGSYADALWWGVVTVTTIGYGDKVPQTW | 323 |
KCNQ2 | IGFLCLILASFLVYLAEKGE---------->N<DHFDTYADALWWGLITLTTIGYGDKYPQTW | 288 |
KCNQ3 | IGFLTLILSSFLVYLVEKDVPEVDAQGEEM>K<EEFETYADALWWGLITLATIGYGDKTPKTW | 327 |
KCNQ4 | IGFLVLIFASFLVYLAEKDA---------->N<SDFSSYADSLWWGTITLTTIGYGDKTPHTW | 294 |
KCNQ5 | IGFLVLIFSSFLVYLVEKDA---------->N<KEFSTYADALWWGTITLTTIGYGDKTPLTW | 322 |
KCNA1 | FLFIGVILFSSAVYFAEAEE---------A>E<SHFSSIPDAFWWAVVSMTTVGYGDMYPVTI | 383 |
KCNA10 | FLFIGVILFSSAVYFAEVDE---------P>E<SHFSSIPDGFWWAVVTMTTVGYGDMCPTTP | 432 |
KCNA2 | FLFIGVILFSSAVYFAEADE---------R>E<SQFPSIPDAFWWAVVSMTTVGYGDMVPTTI | 385 |
KCNA3 | FLFIGVILFSSAVYFAEADD---------P>T<SGFSSIPDAFWWAVVTMTTVGYGDMHPVTI | 455 |
KCNA4 | FLFIGVILFSSAVYFAEADE---------P>T<THFQSIPDAFWWAVVTMTTVGYGDMKPITV | 535 |
KCNA5 | FLFIGVILFSSAVYFAEADN---------Q>G<THFSSIPDAFWWAVVTMTTVGYGDMRPITV | 491 |
KCNA6 | FLFIGVILFSSAVYFAEADD---------D>D<SLFPSIPDAFWWAVVTMTTVGYGDMYPMTV | 433 |
KCNA7 | FLFIGVVLFSSAVYFAEVDR---------V>D<SHFTSIPESFWWAVVTMTTVGYGDMAPVTV | 369 |
KCNB1 | FLAMGIMIFSSLVFFAEKDE---------D>D<TKFKSIPASFWWATITMTTVGYGDIYPKTL | 388 |
KCNB2 | FLAMGIMIFSSLVFFAEKDE---------D>A<TKFTSIPASFWWATITMTTVGYGDIYPKTL | 392 |
KCNC1 | FLALGVLIFATMIYYAERIGAQPNDPSASE>H<THFKNIPIGFWWAVVTMTTLGYGDMYPQTW | 411 |
KCNC2 | FLALGVLIFATMIYYAERVGAQPNDPSASE>H<TQFKNIPIGFWWAVVTMTTLGYGDMYPQTW | 448 |
KCNC3 | FLALGVLIFATMIYYAERIGADPDDILGSN>H<TYFKNIPIGFWWAVVTMTTLGYGDMYPKTW | 514 |
KCNC4 | FLALGVLIFATMIYYAERIGARPSDPRGND>H<TDFKNIPIGFWWAVVTMTTLGYGDMYPKTW | 447 |
KCND1 | SLTMAIIIFATVMFYAEKGT---------N>K<TNFTSIPAAFWYTIVTMTTLGYGDMVPSTI | 383 |
KCND2 | SLTMAIIIFATVMFYAEKGS---------S>A<SKFTSIPAAFWYTIVTMTTLGYGDMVPKTI | 381 |
KCND3 | SLTMAIIIFATVMFYAEKGS---------S>A<SKFTSIPASFWYTIVTMTTLGYGDMVPKTI | 378 |
KCNF1 | YLAVGIFVFSALGYTMEQSH---------P>E<TLFKSIPQSFWWAIITMTTVGYGDIYPKTT | 381 |
KCNG1 | FLCVAIALFAPLLYVIENEM-----A---D>S<PEFTSIPACYWWAVITMTTVGYGDMVPRST | 435 |
KCNG2 | FLCVAMALFAPLVHLAEREL-----G---A>R<RDFSSVPASYWWAVISMTTVGYGDMVPRSL | 380 |
KCNG3 | FICVAMAIFSALSQLLEHGL-----DLETS>N<KDFTSIPAACWWVIISMTTVGYGDMYPITV | 384 |
KCNG4 | FLAVAITLFSPLVYVAEKES-----G---R>V<LEFTSIPASYWWAIISMTTVGYGDMVPRSV | 429 |
KCNS1 | YLAVGVSVFSGVAYTAEKEE---------->D<VGFNTIPACWWWGTVSMTTVGYGDVVPVTV | 432 |
KCNS2 | YLSVGISIFSVVAYTIEKEE---------->N<EGLATIPACWWWATVSMTTVGYGDVVPGTT | 385 |
KCNS3 | FLSVGISIFSVLIYSVEKDD---------H>T<SSLTSIPICWWWATISMTTVGYGDTHPVTL | 381 |
KCNV1 | FLSVGISIFSTVEYFAEQSI---------P>D<TTFTSVPCAWWWATTSMTTVGYGDIRPDTT | 403 |
KCNV2 | FIAMGIFTFSAAVYSVEHDV---------P>S<TNFTTIPHSWWWAAVSISTVGYGDMYPETH | 468 |
cons | > < |
Protein | CDS | Disease Classification | Disease | dbSNP links | Effect Prediction |
---|---|---|---|---|---|
p.R293C | c.877C>T | Inherited Arrhythmia | LQTS | rs199472737 | SIFT: deleterious Polyphen: possibly damaging |
Reports | Inherited Arrhythmia | LQTS | Spectrum and frequency of cardiac channel defects in swimming-triggered arrhythmia syndromes. Circulation. 2004 110(15):2119-24. 15466642 | ||
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 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 | |||
Unknown | Actionable exomic incidental findings in 6503 participants: challenges of variant classification. Genome Res. 2015 25(3):305-15. doi: 10.1101/gr.183483.114. 25637381 | ||||
Inherited Arrhythmia | LQTS | Factors influencing success of clinical genome sequencing across a broad spectrum of disorders. Nat Genet. 2015 47(7):717-26. doi: 10.1038/ng.3304. 25985138 | |||
Inherited Arrhythmia | LQTS | High diagnostic yield of clinical exome sequencing in Middle Eastern patients with Mendelian disorders. Hum Genet. 2015 134(9):967-80. doi: 10.1007/s00439-015-1575-0. 26077850 | |||
p.R293H | c.878G>A | Putative Benign | rs199473465 | SIFT: deleterious Polyphen: benign | |
Reports | Putative Benign | Genetic testing for long-QT syndrome: distinguishing pathogenic mutations from benign variants. Circulation. 2009 120(18):1752-60. 19841300 |