Paralogue Annotation for KCNQ1 residue 374

Residue details

Gene: KCNQ1
Reference Sequences: LRG: LRG_287, Ensembl variant: ENST00000155840 / ENSP00000155840
Amino Acid Position: 374
Reference Amino Acid: L - Leucine
Protein Domain: C-terminus

Paralogue Variants mapped to KCNQ1 residue 374

Paralogue	Variant	Associated Disease	Mapping Quality	Consensus	Pubmed
KCNQ2	L339R	Epilepsy, benign neonatal	Medium	2	11690625

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	ILGSGFALKVQQKQRQKHFNRQIPA--AAS>L<I-QTAWRCY---A-A-ENPD------S---	389
KCNQ2	ILGSGFALKVQEQHRQKHFEKRRNP--AAG>L<I-QSAWRFY---A-T-NLSRTD---LH---	357
KCNQ3	ILGSGLALKVQEQHRQKHFEKRRKP--AAE>L<I-QAAWRYY---A-T-NPNRID---LV---	396
KCNQ4	ILGSGFALKVQEQHRQKHFEKRRMP--AAN>L<I-QAAWRLY---S-T-DMSRAY---LT---	363
KCNQ5	ILGSGFALKVQEQHRQKHFEKRRNP--AAN>L<I-QCVWRSY---A-A-DE-KSV---SI---	390
KCNA1	VIVSNFNYFYHRETEGEEQAQLLH-----V>S<--SP-NLAS---D-S---------------	439
KCNA10	VIVSNFNYFYHRETENEEKQNIPGEIERI->-<------------------------------	483
KCNA2	VIVSNFNYFYHRETEGEEQAQYLQ-----V>T<--SCPKIPS---S-P---------------	442
KCNA3	VIVSNFNYFYHRETEGEEQSQYMH-----V>G<--SCQHLSS-S-A-E---------------	513
KCNA4	VIVSNFNYFYHRETENEEQTQLTQ-----N>A<V-SCPYLPS-N-LLK---------------	595
KCNA5	VIVSNFNYFYHRETDHEEPAVLKEE--QGT>Q<S-QGPGLDR-G-V-Q-R-------------	554
KCNA6	VIVSNFNYFYHRETEQEEQGQYTHV----->-<-------TC-G-------------------	483
KCNA7	VIVSNFSYFYHRETEGEEAGMFSHV----->-<-------DM-Q-P-C---------------	421
KCNB1	IIVNNFSEFYKEQKRQEKAIKRREA--LER>A<--KRNG---SIVS-M-N-------------	449
KCNB2	IIVNNFSEFYKEQKRQEKAIKRREA--LER>A<--KRNG---SIVS-M-N-------------	453
KCNC1	VIVNNFGMYYSLAMAKQKLPKKKKK--HIP>R<--PPQLGSP---N-YCK---S-----V---	475
KCNC2	VIVNNFGMYYSLAMAKQKLPRKRKK--HIP>P<--APQASSP---T-FCK---T-----E---	512
KCNC3	VIVNNFGMYYSLAMAKQKLPKKKNK--HIP>R<--PPQPGSP---N-YCK---PDPPPPPPPH	586
KCNC4	VIVNNFGMYYSLAMAKQKLPKKRKK--HVP>R<--PAQLESP---M-YCK---S-----E---	511
KCND1	VIVSNFSRIYHQNQRADKRRAQQKV--RLA>R<IRLAKSGTT---N---A-------------	445
KCND2	VIVSNFSRIYHQNQRADKRRAQKKA--RLA>R<IRAAKSGSA---N---A-------------	443
KCND3	VIVSNFSRIYHQNQRADKRRAQKKA--RLA>R<IRVAKTGSS---N---A-------------	440
KCNF1	PIINNFVRYYNKQRVLETAAKHELE--LME>L<--N------SSSG-G-E-------------	439
KCNG1	SIFHTFSRSYLELKQEQERVMFRRA--QFL>I<----K-TKSQLSV-----------------	494
KCNG2	SIFHTFSRSYSELKEQQQRAASPEP--ALQ>E<----D-STHSATA-----------------	439
KCNG3	FIYHSFVQCYHELKFRSARYSR-------->-<--------SLSTE-----------------	433
KCNG4	SIFHTFSHSYLELKKEQEQLQARLR--HLQ>N<----T-GPASECE-LLD---P---------	492
KCNS1	IIFNKFSHFYRRQKALEAAVRNSNH--QEF>E<--D------LLSS-I-D-------------	490
KCNS2	LIFNKFSHFYRRQKQLESAMRSCDF--GDG>M<--K------EVPS-V-N-------------	443
KCNS3	IIFNKFSKYYQKQKDIDVDQCSEDA--PEK>C<--H------ELPY-F-N-------------	439
KCNV1	IINDRFSACYFTLKLKEAAVRQREA--LKK>L<--TKNIATDSYIS-V-N-------------	467
KCNV2	ILYNKFSDYYSKLKAYEYTTIRRER--GEV>N<--F------MQRA-R-K-------------	526
cons	> <

See full Alignment of Paralogues

Known Variants in KCNQ1

Protein	CDS	Disease Classification	Disease	dbSNP links	Effect Prediction
p.L374H	c.1121T>A	Inherited Arrhythmia	LQTS	rs199472767	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	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