Paralogue Annotation for KCNQ1 residue 235

Residue details

Gene: KCNQ1
Reference Sequences: LRG: LRG_287, Ensembl variant: ENST00000155840 / ENSP00000155840
Amino Acid Position: 235
Reference Amino Acid: I - Isoleucine
Protein Domain: Transmembrane/Linker/Pore

Paralogue Variants mapped to KCNQ1 residue 235

Paralogue	Variant	Associated Disease	Mapping Quality	Consensus	Pubmed
KCNA1	V299I	Episodic ataxia	Medium	9	19770477
KCNQ2	I205V	Epileptic encephalopathy, neonatal	High	9	22275249, 24318194

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	------------SKGQVFATSAIRGIRFLQ>I<LRMLHVDRQGGTWRLLGSVVFIHRQELITT	265
KCNQ2	------------SQGNVFATSALRSLRFLQ>I<LRMIRMDRRGGTWKLLGSVVYAHSKELVTA	235
KCNQ3	------------NQGNVLA-TSLRSLRFLQ>I<LRMLRMDRRGGTWKLLGSAICAHSKELITA	264
KCNQ4	------------TQGNIFATSALRSMRFLQ>I<LRMVRMDRRGGTWKLLGSVVYAHSKELITA	241
KCNQ5	------------TQGNIFATSALRSLRFLQ>I<LRMVRMDRRGGTWKLLGSVVYAHSKELITA	269
KCNA1	EG-------N-QKGEQATSLAILRVIRLVR>V<FRIFKLSRHSKGLQILGQTLKASMRELGLL	329
KCNA10	TEP---------SAQQNMSLAILRIIRLVR>V<FRIFKLSRHSKGLQILGQTLKASMRELGLL	378
KCNA2	PE-------DAQQGQQAMSLAILRVIRLVR>V<FRIFKLSRHSKGLQILGQTLKASMRELGLL	331
KCNA3	Q----------GNGQQAMSLAILRVIRLVR>V<FRIFKLSRHSKGLQILGQTLKASMRELGLL	401
KCNA4	QGG------GNGQQQQAMSFAILRIIRLVR>V<FRIFKLSRHSKGLQILGHTLRASMRELGLL	481
KCNA5	Q---PGGGGGGQNGQQAMSLAILRVIRLVR>V<FRIFKLSRHSKGLQILGKTLQASMRELGLL	437
KCNA6	QEQQPASGGGGQNGQQAMSLAILRVIRLVR>V<FRIFKLSRHSKGLQILGKTLQASMRELGLL	379
KCNA7	R----------GVGQQAMSLAILRVIRLVR>V<FRIFKLSRHSKGLQILGQTLRASMRELGLL	315
KCNB1	-N--------KSVLQFQNVRRVVQIFRIMR>I<LRILKLARHSTGLQSLGFTLRRSYNELGLL	334
KCNB2	-N--------KSVLQFQNVRRVVQIFRIMR>I<LRILKLARHSTGLQSLGFTLRRSYNELGLL	338
KCNC1	----------LSSKAAKDVLGFLRVVRFVR>I<LRIFKLTRHFVGLRVLGHTLRASTNEFLLL	348
KCNC2	----------LSSKAAKDVLGFLRVVRFVR>I<LRIFKLTRHFVGLRVLGHTLRASTNEFLLL	385
KCNC3	----------LSSKAAKDVLGFLRVVRFVR>I<LRIFKLTRHFVGLRVLGHTLRASTNEFLLL	451
KCNC4	----------LSSKAARDVLGFLRVVRFVR>I<LRIFKLTRHFVGLRVLGHTLRASTNEFLLL	384
KCND1	--------------KNDDVSGAFVTLRVFR>V<FRIFKFSRHSQGLRILGYTLKSCASELGFL	329
KCND2	--------------DNEDVSGAFVTLRVFR>V<FRIFKFSRHSQGLRILGYTLKSCASELGFL	327
KCND3	--------------NNEDVSGAFVTLRVFR>V<FRIFKFSRHSQGLRILGYTLKSCASELGFL	324
KCNF1	---------GARMMELTNVQQAVQALRIMR>I<ARIFKLARHSSGLQTLTYALKRSFKELGLL	327
KCNG1	GRR----KPGAGNSYLDKVGLVLRVLRALR>I<LYVMRLARHSLGLQTLGLTARRCTREFGLL	380
KCNG2	--A----AGPGGTKLLERAGLVLRLLRALR>V<LYVMRLARHSLGLRSLGLTMRRCAREFGLL	325
KCNG3	--------FTGENSQLQRAGVTLRVLRMMR>I<FWVIKLARHFIGLQTLGLTLKRCYREMVML	326
KCNG4	EDG----ERPSGSSYLEKVGLVLRVLRALR>I<LYVMRLARHSLGLQTLGLTVRRCTREFGLL	374
KCNS1	-D--------QGGKEFGHLGKVVQVFRLMR>I<FRVLKLARHSTGLRSLGATLKHSYREVGIL	379
KCNS2	-V--------ESTPTLANLGRVAQVLRLMR>I<FRILKLARHSTGLRSLGATLKYSYKEVGLL	332
KCNS3	-E--------EESEDIENMGKVVQILRLMR>I<FRILKLARHSVGLRSLGATLRHSYHEVGLL	327
KCNV1	-S--------QTTQELENVGRIVQVLRLLR>A<LRMLKLGRHSTGLRSLGMTITQCYEEVGLL	349
KCNV2	EGH----QRGQTVGSVGKVGQVLRVMRLMR>I<FRILKLARHSTGLRAFGFTLRQCYQQVGCL	414
cons	> <

See full Alignment of Paralogues

Known Variants in KCNQ1

Protein	CDS	Disease Classification	Disease	dbSNP links	Effect Prediction
p.I235N	c.704T>A	Inherited Arrhythmia	LQTS	rs199472710	SIFT: deleterious Polyphen: probably 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	Long QT syndrome-associated mutations in the voltage sensor of I(Ks) channels. Cell Physiol Biochem. 2009 24(1-2):11-6. 19590188
		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	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	LQTS	A KCNQ1 mutation contributes to the concealed type 1 long QT phenotype by limiting the Kv7.1 channel conformational changes associated with protein kinase A phosphorylation. Heart Rhythm. 2014 11(3):459-68. doi: 10.1016/j.hrthm.2013.11.021. 24269949