Paralogue Annotation for KCNQ1 residue 122

Residue details

Gene: KCNQ1
Reference Sequences: LRG: LRG_287, Ensembl variant: ENST00000155840 / ENSP00000155840
Amino Acid Position: 122
Reference Amino Acid: C - Cysteine
Protein Domain: Transmembrane/Linker/Pore

Paralogue Variants mapped to KCNQ1 residue 122

Paralogue	Variant	Associated Disease	Mapping Quality	Consensus	Pubmed
KCNV2	A259V	Cone dystrophy with supernormal rod ERG	Medium	8	16909397

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-GWK>C<FVYHFAVFLIVLVCLIFSVLSTIEQYA---	149
KCNQ2	-------------LQNFLYNVLERPR-G-W>A<FIYHAYVFLLVFSCLVLSVFSTIKEYE---	119
KCNQ3	-------------IQTLIYDALERPR-G-W>A<LLYHALVFLIVLGCLILAVLTTFKEYE---	149
KCNQ4	-------------LQNWVYNVLERPR-G-W>A<FVYHVFIFLLVFSCLVLSVLSTIQEHQ---	125
KCNQ5	-------------VQNYLYNVLERPR-G-W>A<FIYHAFVFLLVFGCLILSVFSTIPEHT---	153
KCNA1	--------P-EKEYQRQVWLLFEYPESSGP>A<RVIAIVSVMVILISIVIFCLETLPELKDDK	196
KCNA10	--------P-TNDIHRQFWLLFEYPESSSA>A<RAVAVVSVLVVVISITIFCLETLPEFREDR	245
KCNA2	--------P-ENEFQRQVWLLFEYPESSGP>A<RIIAIVSVMVILISIVSFCLETLPIFRDEN	192
KCNA3	--------P-RRDFQRQVWLLFEYPESSGP>A<RGIAIVSVLVILISIVIFCLETLPEFRDEK	263
KCNA4	--------P-ENEFKKQIWLLFEYPESSSP>A<RGIAIVSVLVILISIVIFCLETLPEFRDDR	336
KCNA5	--------P-RNEFQRQVWLIFEYPESSGS>A<RAIAIVSVLVILISIITFCLETLPEFRDER	279
KCNA6	--------P-SQPFQRQVWLLFEYPESSGP>A<RGIAIVSVLVILISIVIFCLETLPQFRVDG	203
KCNA7	--------P-RRAFARQLWLLFEFPESSQA>A<RVLAVVSVLVILVSIVVFCLETLPDFRDDR	172
KCNB1	----DNTC--CAEKRKKLWDLLEKPNSSVA>A<KILAIISIMFIVLSTIALSLNTLPELQSLD	218
KCNB2	----DNTC--CPDKRKKLWDLLEKPNSSVA>A<KILAIVSILFIVLSTIALSLNTLPELQETD	222
KCNC1	----RPGGF-WRRWQPRIWALFEDPYSSRY>A<RYVAFASLFFILVSITTFCLETHERFNPIV	219
KCNC2	----KSGR--WRRLQPRMWALFEDPYSSRA>A<RFIAFASLFFILVSITTFCLETHEAFNI--	256
KCNC3	GAGGAGGTW-WRRWQPRVWALFEDPYSSRA>A<RYVAFASLFFILISITTFCLETHEGFIHIS	319
KCNC4	----GSGG--CRGWQPRMWALFEDPYSSRA>A<RVVAFASLFFILVSITTFCLETHEAFNI--	253
KCND1	--------PAGSSLRQRLWRAFENPHTSTA>A<LVFYYVTGFFIAVSVIANVVETIPCRGSAR	215
KCND2	--------PTMT-ARQRVWRAFENPHTSTM>A<LVFYYVTGFFIAVSVIANVVETVPCGS-SP	213
KCND3	--------PSLS-FRQTMWRAFENPHTSTL>A<LVFYYVTGFFIAVSVITNVVETVPCGT-VP	211
KCNF1	----AEGR--WRRCQKCVWKFLEKPESSCP>A<RVVAVLSFLLILVSSVVMCMGTIPELQVLD	211
KCNG1	----GEGRL-GR-CMRRLRDMVERPHSGLP>G<KVFACLSVLFVTVTAVNLSVSTLPSLREEE	256
KCNG2	----PRGRL-QR-GRRRLRDVVDNPHSGLA>G<KLFACVSVSFVAVTAVGLCLSTMPDIRAEE	206
KCNG3	----AEAAP-SRRWLERMRRTFEEPTSSLA>A<QILASVSVVFVIVSMVVLCASTLPDWRN-A	199
KCNG4	----HSSRW-GL-CMNRLREMVENPQSGLP>G<KVFACLSILFVATTAVSLCVSTMPDLRAEE	250
KCNS1	----GAAR--CGRLRRRLWLTMENPGYSLP>S<KLFSCVSISVVLASIAAMCIHSLPEYQARE	249
KCNS2	----DGQP--LGNFRRQLWLALDNPGYSVL>S<RVFSILSILVVMGSIITMCLNSLPDFQIPD	216
KCNS3	----DTLR--FGQLRKKIWIRMENPAYCLS>A<KLIAISSLSVVLASIVAMCVHSMSEFQNED	214
KCNV1	----SQGP--CPTVRQKLWNILEKPGSSTA>A<RIFGVISIIFVVVSIINMALMSAEL-----	234
KCNV2	----RDMRF-YGPQRRRLWNLMEKPFSSVA>A<KAIGVASSTFVLVSVVALALNTVEEMQQHS	289
cons	> <

See full Alignment of Paralogues

Known Variants in KCNQ1

Protein	CDS	Disease Classification	Disease	dbSNP links	Effect Prediction
p.C122Y	c.365G>A	Inherited Arrhythmia	LQTS	rs199472681	SIFT: deleterious Polyphen: probably damaging
Reports		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	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