Paralogue Annotation for KCNQ1 residue 300

Residue details

Gene: KCNQ1
Reference Sequences: LRG: LRG_287, Ensembl variant: ENST00000155840 / ENSP00000155840
Amino Acid Position: 300
Reference Amino Acid: A - Alanine
Protein Domain: Transmembrane/Linker/Pore

Paralogue Variants mapped to KCNQ1 residue 300

Paralogue	Variant	Associated Disease	Mapping Quality	Consensus	Pubmed
KCNQ2	A265P	Epileptic encephalopathy, neonatal	High	9	22275249, 24318194
KCNQ2	A265V	Epileptic encephalopathy, early-onset	High	9	22926866
KCNQ2	A265T	Epileptic encephalopathy, early-onset	High	9	23692823

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	FSSYFVYLAEKDAVN-----ESGRVEFGSY>A<DALWWGVVTVTTIGYGDKVPQTWVGKTIAS	330
KCNQ2	LASFLVYLAEKGE----------NDHFDTY>A<DALWWGLITLTTIGYGDKYPQTWNGRLLAA	295
KCNQ3	LSSFLVYLVEKDVPEVDAQGEEMKEEFETY>A<DALWWGLITLATIGYGDKTPKTWEGRLIAA	334
KCNQ4	FASFLVYLAEKDA----------NSDFSSY>A<DSLWWGTITLTTIGYGDKTPHTWLGRVLAA	301
KCNQ5	FSSFLVYLVEKDA----------NKEFSTY>A<DALWWGTITLTTIGYGDKTPLTWLGRLLSA	329
KCNA1	LFSSAVYFAEAEE---------AESHFSSI>P<DAFWWAVVSMTTVGYGDMYPVTIGGKIVGS	390
KCNA10	LFSSAVYFAEVDE---------PESHFSSI>P<DGFWWAVVTMTTVGYGDMCPTTPGGKIVGT	439
KCNA2	LFSSAVYFAEADE---------RESQFPSI>P<DAFWWAVVSMTTVGYGDMVPTTIGGKIVGS	392
KCNA3	LFSSAVYFAEADD---------PTSGFSSI>P<DAFWWAVVTMTTVGYGDMHPVTIGGKIVGS	462
KCNA4	LFSSAVYFAEADE---------PTTHFQSI>P<DAFWWAVVTMTTVGYGDMKPITVGGKIVGS	542
KCNA5	LFSSAVYFAEADN---------QGTHFSSI>P<DAFWWAVVTMTTVGYGDMRPITVGGKIVGS	498
KCNA6	LFSSAVYFAEADD---------DDSLFPSI>P<DAFWWAVVTMTTVGYGDMYPMTVGGKIVGS	440
KCNA7	LFSSAVYFAEVDR---------VDSHFTSI>P<ESFWWAVVTMTTVGYGDMAPVTVGGKIVGS	376
KCNB1	IFSSLVFFAEKDE---------DDTKFKSI>P<ASFWWATITMTTVGYGDIYPKTLLGKIVGG	395
KCNB2	IFSSLVFFAEKDE---------DATKFTSI>P<ASFWWATITMTTVGYGDIYPKTLLGKIVGG	399
KCNC1	IFATMIYYAERIGAQPNDPSASEHTHFKNI>P<IGFWWAVVTMTTLGYGDMYPQTWSGMLVGA	418
KCNC2	IFATMIYYAERVGAQPNDPSASEHTQFKNI>P<IGFWWAVVTMTTLGYGDMYPQTWSGMLVGA	455
KCNC3	IFATMIYYAERIGADPDDILGSNHTYFKNI>P<IGFWWAVVTMTTLGYGDMYPKTWSGMLVGA	521
KCNC4	IFATMIYYAERIGARPSDPRGNDHTDFKNI>P<IGFWWAVVTMTTLGYGDMYPKTWSGMLVGA	454
KCND1	IFATVMFYAEKGT---------NKTNFTSI>P<AAFWYTIVTMTTLGYGDMVPSTIAGKIFGS	390
KCND2	IFATVMFYAEKGS---------SASKFTSI>P<AAFWYTIVTMTTLGYGDMVPKTIAGKIFGS	388
KCND3	IFATVMFYAEKGS---------SASKFTSI>P<ASFWYTIVTMTTLGYGDMVPKTIAGKIFGS	385
KCNF1	VFSALGYTMEQSH---------PETLFKSI>P<QSFWWAIITMTTVGYGDIYPKTTLGKLNAA	388
KCNG1	LFAPLLYVIENEM-----A---DSPEFTSI>P<ACYWWAVITMTTVGYGDMVPRSTPGQVVAL	442
KCNG2	LFAPLVHLAEREL-----G---ARRDFSSV>P<ASYWWAVISMTTVGYGDMVPRSLPGQVVAL	387
KCNG3	IFSALSQLLEHGL-----DLETSNKDFTSI>P<AACWWVIISMTTVGYGDMYPITVPGRILGG	391
KCNG4	LFSPLVYVAEKES-----G---RVLEFTSI>P<ASYWWAIISMTTVGYGDMVPRSVPGQMVAL	436
KCNS1	VFSGVAYTAEKEE----------DVGFNTI>P<ACWWWGTVSMTTVGYGDVVPVTVAGKLAAS	439
KCNS2	IFSVVAYTIEKEE----------NEGLATI>P<ACWWWATVSMTTVGYGDVVPGTTAGKLTAS	392
KCNS3	IFSVLIYSVEKDD---------HTSSLTSI>P<ICWWWATISMTTVGYGDTHPVTLAGKLIAS	388
KCNV1	IFSTVEYFAEQSI---------PDTTFTSV>P<CAWWWATTSMTTVGYGDIRPDTTTGKIVAF	410
KCNV2	TFSAAVYSVEHDV---------PSTNFTTI>P<HSWWWAAVSISTVGYGDMYPETHLGRFFAF	475
cons	> <

See full Alignment of Paralogues

Known Variants in KCNQ1

Protein	CDS	Disease Classification	Disease	dbSNP links	Effect Prediction
p.A300T	c.898G>A	Inherited Arrhythmia	LQTS	rs120074187	SIFT: deleterious Polyphen: probably damaging
Reports		Inherited Arrhythmia	LQTS	A recessive variant of the Romano-Ward long-QT syndrome? Circulation. 1998 97(24):2420-5. 9641694
		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
		Putative Benign		Genetic testing for long-QT syndrome: distinguishing pathogenic mutations from benign variants. Circulation. 2009 120(18):1752-60. 19841300
		Inherited Arrhythmia	LQTS	Low penetrance in the long-QT syndrome: clinical impact. Circulation. 1999 99(4):529-33. 9927399
		Inherited Arrhythmia	LQTS	Structural models for the KCNQ1 voltage-gated potassium channel. Biochemistry. 2007 46(49):14141-52. 17999538
		Putative Benign		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	Mechanisms of I(Ks) suppression in LQT1 mutants. Am J Physiol Heart Circ Physiol. 2000 279(6):H3003-11. 11087258