Paralogue Annotation for KCNQ1 residue 133

Residue details

Gene: KCNQ1
Reference Sequences: LRG: LRG_287, Ensembl variant: ENST00000155840 / ENSP00000155840
Amino Acid Position: 133
Reference Amino Acid: V - Valine
Protein Domain: Transmembrane/Linker/Pore

Paralogue Variants mapped to KCNQ1 residue 133

Paralogue	Variant	Associated Disease	Mapping Quality	Consensus	Pubmed
KCNA1	I177N	Episodic ataxia / myokymia	Medium	9	9600245, 21307345, 12799903

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	--VQGRVYNFLERPT-GWKCFVYHFAVFLI>V<LVCLIFSVLSTIEQYA--------------	149
KCNQ2	--LQNFLYNVLERPR-G-WAFIYHAYVFLL>V<FSCLVLSVFSTIKEYE--------------	119
KCNQ3	--IQTLIYDALERPR-G-WALLYHALVFLI>V<LGCLILAVLTTFKEYE--------------	149
KCNQ4	--LQNWVYNVLERPR-G-WAFVYHVFIFLL>V<FSCLVLSVLSTIQEHQ--------------	125
KCNQ5	--VQNYLYNVLERPR-G-WAFIYHAFVFLL>V<FGCLILSVFSTIPEHT--------------	153
KCNA1	KEYQRQVWLLFEYPESSGPARVIAIVSVMV>I<LISIVIFCLETLPELKDDK-DF--------	198
KCNA10	NDIHRQFWLLFEYPESSSAARAVAVVSVLV>V<VISITIFCLETLPEFREDR-EL--------	247
KCNA2	NEFQRQVWLLFEYPESSGPARIIAIVSVMV>I<LISIVSFCLETLPIFRDEN-ED--------	194
KCNA3	RDFQRQVWLLFEYPESSGPARGIAIVSVLV>I<LISIVIFCLETLPEFRDEK-DY--------	265
KCNA4	NEFKKQIWLLFEYPESSSPARGIAIVSVLV>I<LISIVIFCLETLPEFRDDR-DL--------	338
KCNA5	NEFQRQVWLIFEYPESSGSARAIAIVSVLV>I<LISIITFCLETLPEFRDER-ELLRHPPAP-	288
KCNA6	QPFQRQVWLLFEYPESSGPARGIAIVSVLV>I<LISIVIFCLETLPQFRVDG-RGGNNGGVSR	213
KCNA7	RAFARQLWLLFEFPESSQAARVLAVVSVLV>I<LVSIVVFCLETLPDFRDDR-DGTGL-----	177
KCNB1	AEKRKKLWDLLEKPNSSVAAKILAIISIMF>I<VLSTIALSLNTLPELQSLD-EF--------	220
KCNB2	PDKRKKLWDLLEKPNSSVAAKILAIVSILF>I<VLSTIALSLNTLPELQETD-EF--------	224
KCNC1	RRWQPRIWALFEDPYSSRYARYVAFASLFF>I<LVSITTFCLETHERFNPIV-NK--------	221
KCNC2	RRLQPRMWALFEDPYSSRAARFIAFASLFF>I<LVSITTFCLETHEAFNI---VK--------	258
KCNC3	RRWQPRVWALFEDPYSSRAARYVAFASLFF>I<LISITTFCLETHEGFIHIS-NK--------	321
KCNC4	RGWQPRMWALFEDPYSSRAARVVAFASLFF>I<LVSITTFCLETHEAFNI---DR-NV-----	257
KCND1	SSLRQRLWRAFENPHTSTAALVFYYVTGFF>I<AVSVIANVVETIPCRGSAR-RS--------	217
KCND2	T-ARQRVWRAFENPHTSTMALVFYYVTGFF>I<AVSVIANVVETVPCGS-SP-GH--------	215
KCND3	S-FRQTMWRAFENPHTSTLALVFYYVTGFF>I<AVSVITNVVETVPCGT-VP-G---------	212
KCNF1	RRCQKCVWKFLEKPESSCPARVVAVLSFLL>I<LVSSVVMCMGTIPELQVLD-AE--------	213
KCNG1	R-CMRRLRDMVERPHSGLPGKVFACLSVLF>V<TVTAVNLSVSTLPSLREEEE-Q--------	258
KCNG2	R-GRRRLRDVVDNPHSGLAGKLFACVSVSF>V<AVTAVGLCLSTMPDIRAEEE-R--------	208
KCNG3	RRWLERMRRTFEEPTSSLAAQILASVSVVF>V<IVSMVVLCASTLPDWRN-AAAD--------	202
KCNG4	L-CMNRLREMVENPQSGLPGKVFACLSILF>V<ATTAVSLCVSTMPDLRAEED-Q--------	252
KCNS1	GRLRRRLWLTMENPGYSLPSKLFSCVSISV>V<LASIAAMCIHSLPEYQARE-AA--------	251
KCNS2	GNFRRQLWLALDNPGYSVLSRVFSILSILV>V<MGSIITMCLNSLPDFQIPD-SQ--------	218
KCNS3	GQLRKKIWIRMENPAYCLSAKLIAISSLSV>V<LASIVAMCVHSMSEFQNED-GE--------	216
KCNV1	PTVRQKLWNILEKPGSSTAARIFGVISIIF>V<VVSIINMALMSAEL----------------	234
KCNV2	GPQRRRLWNLMEKPFSSVAAKAIGVASSTF>V<LVSVVALALNTVEEMQQHS-GQ--------	291
cons	> <

See full Alignment of Paralogues

Known Variants in KCNQ1

Protein	CDS	Disease Classification	Disease	dbSNP links	Effect Prediction
p.V133I	c.397G>A	Inherited Arrhythmia	LQTS	rs199473449	SIFT: deleterious Polyphen: probably damaging
Reports		Inherited Arrhythmia	LQTS	Catecholamine-provoked microvoltage T wave alternans in genotyped long QT syndrome. Pacing Clin Electrophysiol. 2003 26(8):1660-7. 12877697
		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