Paralogue Annotation for KCNQ1 residue 144

Residue details

Gene: KCNQ1
Reference Sequences: LRG: LRG_287, Ensembl variant: ENST00000155840 / ENSP00000155840
Amino Acid Position: 144
Reference Amino Acid: T - Threonine
Protein Domain: Transmembrane/Linker/Pore

Paralogue Variants mapped to KCNQ1 residue 144

Paralogue	Variant	Associated Disease	Mapping Quality	Consensus	Pubmed
KCNQ2	T114I	Epileptic encephalopathy, early-onset	High	9	22926866
KCNQ2	T114A	Epilepsy, benign neonatal	High	9	25982755

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	ERPT-GWKCFVYHFAVFLIVLVCLIFSVLS>T<IEQYA-------------------------	149
KCNQ2	ERPR-G-WAFIYHAYVFLLVFSCLVLSVFS>T<IKEYE-------------------------	119
KCNQ3	ERPR-G-WALLYHALVFLIVLGCLILAVLT>T<FKEYE-------------------------	149
KCNQ4	ERPR-G-WAFVYHVFIFLLVFSCLVLSVLS>T<IQEHQ-------------------------	125
KCNQ5	ERPR-G-WAFIYHAFVFLLVFGCLILSVFS>T<IPEHT-------------------------	153
KCNA1	EYPESSGPARVIAIVSVMVILISIVIFCLE>T<LPELKDDK-DF--------TG---------	200
KCNA10	EYPESSSAARAVAVVSVLVVVISITIFCLE>T<LPEFREDR-EL--------KV---------	249
KCNA2	EYPESSGPARIIAIVSVMVILISIVSFCLE>T<LPIFRDEN-ED--------MHGSG---V--	200
KCNA3	EYPESSGPARGIAIVSVLVILISIVIFCLE>T<LPEFRDEK-DY--------PA-ST---SQD	272
KCNA4	EYPESSSPARGIAIVSVLVILISIVIFCLE>T<LPEFRDDR-DL--------VM-AL---SAG	345
KCNA5	EYPESSGSARAIAIVSVLVILISIITFCLE>T<LPEFRDER-ELLRHPPAP---------HQP	291
KCNA6	EYPESSGPARGIAIVSVLVILISIVIFCLE>T<LPQFRVDG-RGGNNGGVSRVS-PVSRGSQE	223
KCNA7	EFPESSQAARVLAVVSVLVILVSIVVFCLE>T<LPDFRDDR-DGTGL-----AA-AA---AAG	184
KCNB1	EKPNSSVAAKILAIISIMFIVLSTIALSLN>T<LPELQSLD-EF--------GQ---------	222
KCNB2	EKPNSSVAAKILAIVSILFIVLSTIALSLN>T<LPELQETD-EF--------GQ---------	226
KCNC1	EDPYSSRYARYVAFASLFFILVSITTFCLE>T<HERFNPIV-NK--------TE-I----E--	225
KCNC2	EDPYSSRAARFIAFASLFFILVSITTFCLE>T<HEAFNI---VK--------NK-T----E--	262
KCNC3	EDPYSSRAARYVAFASLFFILISITTFCLE>T<HEGFIHIS-NK--------TV-T----QA-	326
KCNC4	EDPYSSRAARVVAFASLFFILVSITTFCLE>T<HEAFNI---DR-NV-----TE-I----L--	261
KCND1	ENPHTSTAALVFYYVTGFFIAVSVIANVVE>T<IPCRGSAR-RS--------SR---------	219
KCND2	ENPHTSTMALVFYYVTGFFIAVSVIANVVE>T<VPCGS-SP-GH--------IK---------	217
KCND3	ENPHTSTLALVFYYVTGFFIAVSVITNVVE>T<VPCGT-VP-G---------SK---------	214
KCNF1	EKPESSCPARVVAVLSFLLILVSSVVMCMG>T<IPELQVLD-AE--------GN---------	215
KCNG1	ERPHSGLPGKVFACLSVLFVTVTAVNLSVS>T<LPSLREEEE-Q--------GH---------	260
KCNG2	DNPHSGLAGKLFACVSVSFVAVTAVGLCLS>T<MPDIRAEEE-R--------GE---------	210
KCNG3	EEPTSSLAAQILASVSVVFVIVSMVVLCAS>T<LPDWRN-AAAD--------NR---------	204
KCNG4	ENPQSGLPGKVFACLSILFVATTAVSLCVS>T<MPDLRAEED-Q--------GE---------	254
KCNS1	ENPGYSLPSKLFSCVSISVVLASIAAMCIH>S<LPEYQARE-AA--------AA---------	253
KCNS2	DNPGYSVLSRVFSILSILVVMGSIITMCLN>S<LPDFQIPD-SQ--------GN---------	220
KCNS3	ENPAYCLSAKLIAISSLSVVLASIVAMCVH>S<MSEFQNED-GE-------------------	216
KCNV1	EKPGSSTAARIFGVISIIFVVVSIINMALM>S<AEL-----------------S---------	235
KCNV2	EKPFSSVAAKAIGVASSTFVLVSVVALALN>T<VEEMQQHS-GQ--------GE---------	293
cons	> <

See full Alignment of Paralogues

Known Variants in KCNQ1

Protein	CDS	Disease Classification	Disease	dbSNP links	Effect Prediction
p.T144A	c.430A>G	Inherited Arrhythmia	LQTS	rs199473451	SIFT: deleterious Polyphen: probably damaging
Reports		Inherited Arrhythmia	LQTS	Location of mutation in the KCNQ1 and phenotypic presentation of long QT syndrome. J Cardiovasc Electrophysiol. 2003 14(11):1149-53. 14678125
		Inherited Arrhythmia	LQTS	Whole blood RNA offers a rapid, comprehensive approach to genetic diagnosis of cardiovascular diseases. Genet Med. 2007 9(1):23-33. 17224687
		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	Clinical aspects of type-1 long-QT syndrome by location, coding type, and biophysical function of mutations involving the KCNQ1 gene. Circulation. 2007 115(19):2481-9. 17470695