Paralogue Annotation for KCNQ1 residue 46

Residue details

Gene: KCNQ1
Reference Sequences: LRG: LRG_287, Ensembl variant: ENST00000155840 / ENSP00000155840
Amino Acid Position: 46
Reference Amino Acid: A - Alanine
Protein Domain: N-terminus

Paralogue Variants mapped to KCNQ1 residue 46

Paralogue	Variant	Associated Disease	Mapping Quality	Consensus	Pubmed
KCNC3	D129N	Spinocerebellar ataxia 13	Medium	7	25756792, 25756792

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	----GG--P--------------------->A<--GGALYAPIAPGAPGP--------APPAS	66
KCNQ2	----GS--E--------------------->-<-----------A-PK---------------	49
KCNQ3	----GG--R--------------------->-<---------------DEG-----QR---R-	80
KCNQ4	----GS--P--------------------->-<---------RRLGLLGSP-----L------	52
KCNQ5	----TR--A--------------------->-<---------ATLGGGGGG-----LRESRRG	81
KCNA1	PK------------------KR-M---RYF>D<PLRNEYFFDRNRPSFDAILYYYQSGGRLRR	104
KCNA10	RE------------------KR-M---QFF>D<SMRNEYFFDRNRPSFDGILYYYQSGGKIRR	153
KCNA2	PK------------------KR-M---RYF>D<PLRNEYFFDRNRPSFDAILYYYQSGGRLRR	100
KCNA3	PK------------------RR-M---RYF>D<PLRNEYFFDRNRPSFDAILYYYQSGGRIRR	171
KCNA4	PE------------------KR-T---QYF>D<PLRNEYFFDRNRPSFDAILYYYQSGGRLKR	243
KCNA5	PA------------------KR-L---RYF>D<PLRNEYFFDRNRPSFDGILYYYQSGGRLRR	187
KCNA6	PG------------------RR-V---RFF>D<PLRNEYFFDRNRPSFDAILYYYQSGGRLRR	108
KCNA7	PA------------------RR-G---RFY>D<DARREYFFDRHRPSFDAVLYYYQSGGRLRR	80
KCNB1	LRDCNT--HD----------SL-LEVCDDY>S<LDDNEYFFDRHPGAFTSILNFYRT-GRLHM	106
KCNB2	LRDCNT--HE----------SL-LEVCDDY>N<LNENEYFFDRHPGAFTSILNFYRT-GKLHM	110
KCNC1	-----------------------S--HFDY>D<PRADEFFFDRHPGVFAHILNYYRT-GKLHC	78
KCNC2	SS------------------RGGR--ASDH>P<GGGREFFFDRHPGVFAYVLNYYRT-GKLHC	125
KCNC3	-----------------------A--RFDY>D<PGADEFFFDRHPGVFAYVLNYYRT-GKLHC	158
KCNC4	----------------------GS--SGSS>G<GGGCEFFFDRHPGVFAYVLNYYRT-GKLHC	117
KCND1	SE------------------KE-F----FY>D<ADSGEYFFDRDPDMFRHVLNFYRT-GRLHC	105
KCND2	SE------------------RD-F----FY>H<PETQQYFFDRDPDIFRHILNFYRT-GKLHY	106
KCND3	TE------------------KE-F----FF>N<EDTKEYFFDRDPEVFRCVLNFYRT-GKLHY	105
KCNF1	LINCLAGGYD----------TI-FSLCDDY>D<PGKREFYFDRDPDAFKCVIEVYYF-GEVHM	100
KCNG1	LKACTN--FD----------DI-LNVCDDY>D<VTCNEFFFDRNPGAFGTILTFLRA-GKLRL	138
KCNG2	LRACRG--HD----------DL-LRVCDDY>D<VSRDEFFFDRSPCAFRAIVALLRA-GKLRL	92
KCNG3	LHGCRS--ER----------DV-LEVCDDY>D<RERNEYFFDRHSEAFGFILLYVRGHGKLRF	85
KCNG4	LRLCRS--YE----------EI-VQLCDDY>D<EDSQEFFFDRSPSAFGVIVSFLAA-GKLVL	134
KCNS1	LQAAAS--EE----------QA-RRLCDDY>D<EAAREFYFDRHPGFFLSLLHFYRT-GHLHV	125
KCNS2	LLLCHS--RE----------AI-LELCDDY>D<DVQREFYFDRNPELFPYVLHFYHT-GKLHV	92
KCNS3	LLTCHS--EE----------AI-LELCDDY>S<VADKEYYFDRNPSLFRYVLNFYYT-GKLHV	90
KCNV1	LAVVVA--SYRRPGALAAVPSP-LELCDDA>N<PVDNEYFFDRSSQAFRYVLHYYRT-GRLHV	124
KCNV2	LATSTS--RS----------RQ-LSLCDDY>E<EQTDEYFFDRDPAVFQLVYNFYLS-GVLLV	172
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See full Alignment of Paralogues

Known Variants in KCNQ1

Protein	CDS	Disease Classification	Disease	dbSNP links	Effect Prediction
p.A46T	c.136G>A	Inherited Arrhythmia	LQTS,AF	rs199473671	SIFT: tolerated Polyphen: benign
Reports		Inherited Arrhythmia	LQTS	Genetic testing in the long QT syndrome: development and validation of an efficient approach to genotyping in clinical practice. JAMA. 2005 294(23):2975-80. 16414944
		Inherited Arrhythmia	LQTS	Long QT and Brugada syndrome gene mutations in New Zealand. Heart Rhythm. 2007 4(10):1306-14. 17905336
		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	Biophysical properties of 9 KCNQ1 mutations associated with long-QT syndrome. Circ Arrhythm Electrophysiol. 2009 2(4):417-26. 19808498
		Inherited Arrhythmia	AF	Very early-onset lone atrial fibrillation patients have a high prevalence of rare variants in genes previously associated with atrial fibrillation. Heart Rhythm. 2014 11(2):246-51. doi: 10.1016/j.hrthm.2013.10.034. 24144883
		Other Disease Phenotype		Genetic and forensic implications in epilepsy and cardiac arrhythmias: a case series. Int J Legal Med. 2014 25119684
		Inherited Arrhythmia	LQTS	IKs Gain- and Loss-of-Function in Early-Onset Lone Atrial Fibrillation. J Cardiovasc Electrophysiol. 2015 26(7):715-23. doi: 10.1111/jce.12666. 25786344