Paralogue Annotation for KCNQ1 residue 309

Residue details

Gene: KCNQ1
Reference Sequences: LRG: LRG_287, Ensembl variant: ENST00000155840 / ENSP00000155840
Amino Acid Position: 309
Reference Amino Acid: T - Threonine
Protein Domain: Transmembrane/Linker/Pore

Paralogue Variants mapped to KCNQ1 residue 309

Paralogue	Variant	Associated Disease	Mapping Quality	Consensus	Pubmed
KCNQ2	T274M	Epileptic encephalopathy, neonatal	High	9	22275249, 24318194
KCNB1	T374I	Epileptic encephalopathy	High	9	25164438, 25164438

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	EKDAVN-----ESGRVEFGSYADALWWGVV>T<VTTIGYGDKVPQTWVGKTIASCFSVFAISF	339
KCNQ2	EKGE----------NDHFDTYADALWWGLI>T<LTTIGYGDKYPQTWNGRLLAATFTLIGVSF	304
KCNQ3	EKDVPEVDAQGEEMKEEFETYADALWWGLI>T<LATIGYGDKTPKTWEGRLIAATFSLIGVSF	343
KCNQ4	EKDA----------NSDFSSYADSLWWGTI>T<LTTIGYGDKTPHTWLGRVLAAGFALLGISF	310
KCNQ5	EKDA----------NKEFSTYADALWWGTI>T<LTTIGYGDKTPLTWLGRLLSAGFALLGISF	338
KCNA1	EAEE---------AESHFSSIPDAFWWAVV>S<MTTVGYGDMYPVTIGGKIVGSLCAIAGVLT	399
KCNA10	EVDE---------PESHFSSIPDGFWWAVV>T<MTTVGYGDMCPTTPGGKIVGTLCAIAGVLT	448
KCNA2	EADE---------RESQFPSIPDAFWWAVV>S<MTTVGYGDMVPTTIGGKIVGSLCAIAGVLT	401
KCNA3	EADD---------PTSGFSSIPDAFWWAVV>T<MTTVGYGDMHPVTIGGKIVGSLCAIAGVLT	471
KCNA4	EADE---------PTTHFQSIPDAFWWAVV>T<MTTVGYGDMKPITVGGKIVGSLCAIAGVLT	551
KCNA5	EADN---------QGTHFSSIPDAFWWAVV>T<MTTVGYGDMRPITVGGKIVGSLCAIAGVLT	507
KCNA6	EADD---------DDSLFPSIPDAFWWAVV>T<MTTVGYGDMYPMTVGGKIVGSLCAIAGVLT	449
KCNA7	EVDR---------VDSHFTSIPESFWWAVV>T<MTTVGYGDMAPVTVGGKIVGSLCAIAGVLT	385
KCNB1	EKDE---------DDTKFKSIPASFWWATI>T<MTTVGYGDIYPKTLLGKIVGGLCCIAGVLV	404
KCNB2	EKDE---------DATKFTSIPASFWWATI>T<MTTVGYGDIYPKTLLGKIVGGLCCIAGVLV	408
KCNC1	ERIGAQPNDPSASEHTHFKNIPIGFWWAVV>T<MTTLGYGDMYPQTWSGMLVGALCALAGVLT	427
KCNC2	ERVGAQPNDPSASEHTQFKNIPIGFWWAVV>T<MTTLGYGDMYPQTWSGMLVGALCALAGVLT	464
KCNC3	ERIGADPDDILGSNHTYFKNIPIGFWWAVV>T<MTTLGYGDMYPKTWSGMLVGALCALAGVLT	530
KCNC4	ERIGARPSDPRGNDHTDFKNIPIGFWWAVV>T<MTTLGYGDMYPKTWSGMLVGALCALAGVLT	463
KCND1	EKGT---------NKTNFTSIPAAFWYTIV>T<MTTLGYGDMVPSTIAGKIFGSICSLSGVLV	399
KCND2	EKGS---------SASKFTSIPAAFWYTIV>T<MTTLGYGDMVPKTIAGKIFGSICSLSGVLV	397
KCND3	EKGS---------SASKFTSIPASFWYTIV>T<MTTLGYGDMVPKTIAGKIFGSICSLSGVLV	394
KCNF1	EQSH---------PETLFKSIPQSFWWAII>T<MTTVGYGDIYPKTTLGKLNAAISFLCGVIA	397
KCNG1	ENEM-----A---DSPEFTSIPACYWWAVI>T<MTTVGYGDMVPRSTPGQVVALSSILSGILL	451
KCNG2	EREL-----G---ARRDFSSVPASYWWAVI>S<MTTVGYGDMVPRSLPGQVVALSSILSGILL	396
KCNG3	EHGL-----DLETSNKDFTSIPAACWWVII>S<MTTVGYGDMYPITVPGRILGGVCVVSGIVL	400
KCNG4	EKES-----G---RVLEFTSIPASYWWAII>S<MTTVGYGDMVPRSVPGQMVALSSILSGILI	445
KCNS1	EKEE----------DVGFNTIPACWWWGTV>S<MTTVGYGDVVPVTVAGKLAASGCILGGILV	448
KCNS2	EKEE----------NEGLATIPACWWWATV>S<MTTVGYGDVVPGTTAGKLTASACILAGILV	401
KCNS3	EKDD---------HTSSLTSIPICWWWATI>S<MTTVGYGDTHPVTLAGKLIASTCIICGILV	397
KCNV1	EQSI---------PDTTFTSVPCAWWWATT>S<MTTVGYGDIRPDTTTGKIVAFMCILSGILV	419
KCNV2	EHDV---------PSTNFTTIPHSWWWAAV>S<ISTVGYGDMYPETHLGRFFAFLCIAFGIIL	484
cons	> <

See full Alignment of Paralogues

Known Variants in KCNQ1

Protein	CDS	Disease Classification	Disease	dbSNP links	Effect Prediction
p.T309I	c.926C>T	Inherited Arrhythmia	LQTS	rs199472743	SIFT: deleterious Polyphen: probably damaging
Reports		Inherited Arrhythmia	LQTS	Linkage and mutation analysis in two Taiwanese families with long QT syndrome. J Formos Med Assoc. 2001 100(11):767-71. 11802537
p.T309R	c.926C>G	Inherited Arrhythmia	LQTS	rs199472743	SIFT: deleterious Polyphen: probably damaging
Reports		Inherited Arrhythmia	LQTS	KVLQT1 C-terminal missense mutation causes a forme fruste long-QT syndrome. Circulation. 1997 96(9):2778-81. 9386136
p.T309S	c.925A>T	Inherited Arrhythmia	LQTS	rs199473468	SIFT: deleterious Polyphen: probably damaging
Reports		Inherited Arrhythmia	LQTS	Automated mutation screening using dideoxy fingerprinting and capillary array electrophoresis. Hum Mutat. 2001 18(5):451-7. 11668638