Paralogue Annotation for KCNQ1 residue 372

Residue details

Gene: KCNQ1
Reference Sequences: LRG: LRG_287, Ensembl variant: ENST00000155840 / ENSP00000155840
Amino Acid Position: 372
Reference Amino Acid: A - Alanine
Protein Domain: C-terminus

Paralogue Variants mapped to KCNQ1 residue 372

Paralogue	Variant	Associated Disease	Mapping Quality	Consensus	Pubmed
KCNQ2	A337G	Epileptic encephalopathy, early-onset	Medium	3	22926866

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	AGILGSGFALKVQQKQRQKHFNRQIPA--A>A<SLI-QTAWRCY---A-A-ENPD------S-	389
KCNQ2	AGILGSGFALKVQEQHRQKHFEKRRNP--A>A<GLI-QSAWRFY---A-T-NLSRTD---LH-	357
KCNQ3	AGILGSGLALKVQEQHRQKHFEKRRKP--A>A<ELI-QAAWRYY---A-T-NPNRID---LV-	396
KCNQ4	AGILGSGFALKVQEQHRQKHFEKRRMP--A>A<NLI-QAAWRLY---S-T-DMSRAY---LT-	363
KCNQ5	AGILGSGFALKVQEQHRQKHFEKRRNP--A>A<NLI-QCVWRSY---A-A-DE-KSV---SI-	390
KCNA1	VPVIVSNFNYFYHRETEGEEQAQLLH---->-<VS--SP-NLAS---D-S-------------	439
KCNA10	VPVIVSNFNYFYHRETENEEKQNIPGEIER>I<------------------------------	483
KCNA2	VPVIVSNFNYFYHRETEGEEQAQYLQ---->-<VT--SCPKIPS---S-P-------------	442
KCNA3	VPVIVSNFNYFYHRETEGEEQSQYMH---->-<VG--SCQHLSS-S-A-E-------------	513
KCNA4	VPVIVSNFNYFYHRETENEEQTQLTQ---->-<NAV-SCPYLPS-N-LLK-------------	595
KCNA5	VPVIVSNFNYFYHRETDHEEPAVLKEE--Q>G<TQS-QGPGLDR-G-V-Q-R-----------	554
KCNA6	VPVIVSNFNYFYHRETEQEEQGQYTHV--->-<---------TC-G-----------------	483
KCNA7	VPVIVSNFSYFYHRETEGEEAGMFSHV--->-<---------DM-Q-P-C-------------	421
KCNB1	IPIIVNNFSEFYKEQKRQEKAIKRREA--L>E<RA--KRNG---SIVS-M-N-----------	449
KCNB2	IPIIVNNFSEFYKEQKRQEKAIKRREA--L>E<RA--KRNG---SIVS-M-N-----------	453
KCNC1	VPVIVNNFGMYYSLAMAKQKLPKKKKK--H>I<PR--PPQLGSP---N-YCK---S-----V-	475
KCNC2	VPVIVNNFGMYYSLAMAKQKLPRKRKK--H>I<PP--APQASSP---T-FCK---T-----E-	512
KCNC3	VPVIVNNFGMYYSLAMAKQKLPKKKNK--H>I<PR--PPQPGSP---N-YCK---PDPPPPPP	584
KCNC4	VPVIVNNFGMYYSLAMAKQKLPKKRKK--H>V<PR--PAQLESP---M-YCK---S-----E-	511
KCND1	VPVIVSNFSRIYHQNQRADKRRAQQKV--R>L<ARIRLAKSGTT---N---A-----------	445
KCND2	VPVIVSNFSRIYHQNQRADKRRAQKKA--R>L<ARIRAAKSGSA---N---A-----------	443
KCND3	VPVIVSNFSRIYHQNQRADKRRAQKKA--R>L<ARIRVAKTGSS---N---A-----------	440
KCNF1	IHPIINNFVRYYNKQRVLETAAKHELE--L>M<EL--N------SSSG-G-E-----------	439
KCNG1	VTSIFHTFSRSYLELKQEQERVMFRRA--Q>F<LI----K-TKSQLSV---------------	494
KCNG2	VTSIFHTFSRSYSELKEQQQRAASPEP--A>L<QE----D-STHSATA---------------	439
KCNG3	ITFIYHSFVQCYHELKFRSARYSR------>-<----------SLSTE---------------	433
KCNG4	ATSIFHTFSHSYLELKKEQEQLQARLR--H>L<QN----T-GPASECE-LLD---P-------	492
KCNS1	ITIIFNKFSHFYRRQKALEAAVRNSNH--Q>E<FE--D------LLSS-I-D-----------	490
KCNS2	ITLIFNKFSHFYRRQKQLESAMRSCDF--G>D<GM--K------EVPS-V-N-----------	443
KCNS3	ITIIFNKFSKYYQKQKDIDVDQCSEDA--P>E<KC--H------ELPY-F-N-----------	439
KCNV1	IAIINDRFSACYFTLKLKEAAVRQREA--L>K<KL--TKNIATDSYIS-V-N-----------	467
KCNV2	ISILYNKFSDYYSKLKAYEYTTIRRER--G>E<VN--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.A372D	c.1115C>A	Inherited Arrhythmia	LQTS	rs199473472	SIFT: deleterious Polyphen: probably damaging
Reports		Inherited Arrhythmia	LQTS	Genetic testing in the long QT syndrome: development and validation of an efficient approach to genotyping in clinical practice. JAMA. 2005 294(23):2975-80. 16414944