Paralogue Annotation for KCNQ1 residue 205

Residue details

Gene: KCNQ1
Reference Sequences: LRG: LRG_287, Ensembl variant: ENST00000155840 / ENSP00000155840
Amino Acid Position: 205
Reference Amino Acid: V - Valine
Protein Domain: Transmembrane/Linker/Pore

Paralogue Variants mapped to KCNQ1 residue 205

Paralogue	Variant	Associated Disease	Mapping Quality	Consensus	Pubmed
KCNQ2	V175L	Epileptic encephalopathy, early-onset	High	9	23692823, 27030113
KCNQ2	V175L	West syndrome	High	9	25092550

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	LWSAGCRSKYVGLWGRLRFARKPISIIDLI>V<VVASMVVLCVG----------------SKG	219
KCNQ2	IWAAGCCCRYRGWRGRLKFARKPFCVIDIM>V<LIASIAVLAAG----------------SQG	189
KCNQ3	IWAAGCCCRYKGWRGRLKFARKPLCMLDIF>V<LIASVPVVAVG----------------NQG	219
KCNQ4	VWSAGCCCRYRGWQGRFRFARKPFCVIDFI>V<FVASVAVIAAG----------------TQG	195
KCNQ5	IWSAGCCCRYRGWQGRLRFARKPFCVIDTI>V<LIASIAVVSAK----------------TQG	223
KCNA1	---------FFACPSKTDFFKNIMNFIDIV>A<IIPYFITLGTEIAEQEG-------N-QKGE	283
KCNA10	---------FVVCPSKTDFFRNIMNIIDII>S<IIPYFATLITELVQETEP---------SAQ	332
KCNA2	---------FFACPSKAGFFTNIMNIIDIV>A<IIPYFITLGTELAEKPE-------DAQQGQ	285
KCNA3	---------FFACPSKATFSRNIMNLIDIV>A<IIPYFITLGTELAERQ----------GNGQ	355
KCNA4	---------CFACPSQALFFKNIMNIIDIV>S<ILPYFITLGTDLAQQQGG------GNGQQQ	435
KCNA5	---------FFACPSKAGFSRNIMNIIDVV>A<IFPYFITLGTELAEQQ---PGGGGGGQNGQ	391
KCNA6	---------FSACPSKPAFFRNIMNIIDLV>A<IFPYFITLGTELVQQQEQQPASGGGGQNGQ	333
KCNA7	---------LLVCPSKAIFFKNVMNLIDFV>A<ILPYFVALGTELARQR----------GVGQ	269
KCNB1	---------FLSSPKKWKFFKGPLNAIDLL>A<ILPYYVTIFLTES---N--------KSVLQ	288
KCNB2	---------FLSSPNKWKFFKGPLNVIDLL>A<ILPYYVTIFLTES---N--------KSVLQ	292
KCNC1	---------VIFCPNKVEFIKNSLNIIDFV>A<ILPFYLEVGLSG-------------LSSKA	302
KCNC2	---------IVFSPNKLEFIKNLLNIIDFV>A<ILPFYLEVGLSG-------------LSSKA	339
KCNC3	---------ITFCPDKVEFLKSSLNIIDCV>A<ILPFYLEVGLSG-------------LSSKA	405
KCNC4	---------IVCCPDTLDFVKNLLNIIDFV>A<ILPFYLEVGLSG-------------LSSKA	338
KCND1	---------LFAAPSRCRFLRSVMSLIDVV>A<ILPYYIGLLVP------------------K	283
KCND2	---------LAAAPSRYRFVRSVMSIIDVV>A<ILPYYIGLVMT------------------D	281
KCND3	---------LFAAPSRYRFIRSVMSIIDVV>A<IMPYYIGLVMT------------------N	278
KCNF1	---------LFSSPNKLHFALSFMNIVDVL>A<ILPFYVSLTLTHL-----------GARMME	281
KCNG1	---------LIQAPSKFAFLRSPLTLIDLV>A<ILPYYITLLVDGAAAGRR----KPGAGNSY	334
KCNG2	---------SLQAESKCAFLRAPLNIIDIL>A<LLPFYVSLLLGL-----A----AGPGGTKL	279
KCNG3	---------FIVSKNKCEFVKRPLNIIDLL>A<ITPYYISVLMTV-----------FTGENSQ	280
KCNG4	---------FVQAQDKCQFFQGPLNIIDIL>A<ISPYYVSLAVSEEPPEDG----ERPSGSSY	328
KCNS1	---------LLLAPSTRNFFCHPLNLIDIV>S<VLPFYLTLLAGVALG-D--------QGGKE	333
KCNS2	---------FAVAPDFLKFFKNALNLIDLM>S<IVPFYITLVVNLV---V--------ESTPT	286
KCNS3	---------LAAAPCQKKFWKNPLNIIDFV>S<IIPFYATLAVDTK---E--------EESED	281
KCNV1	---------FLCVRDRCRFLRKVPNIIDLL>A<ILPFYITLLVESLSG-S--------QTTQE	303
KCNV2	---------LASTPDLRRFARSALNLVDLV>A<ILPLYLQLLLECFTGEGH----QRGQTVGS	368
cons	> <

See full Alignment of Paralogues

Known Variants in KCNQ1

Protein	CDS	Disease Classification	Disease	dbSNP links	Effect Prediction
p.V205M	c.613G>A	Inherited Arrhythmia	LQTS	rs151344631	SIFT: deleterious Polyphen: probably damaging
Reports		Inherited Arrhythmia	LQTS	A KCNQ1 V205M missense mutation causes a high rate of long QT syndrome in a First Nations community of northern British Columbia: a community-based approach to understanding the impact. Genet Med. 2008 10(7):545-50. 18580685
		Inherited Arrhythmia	LQTS	Mechanistic basis for LQT1 caused by S3 mutations in the KCNQ1 subunit of IKs. J Gen Physiol. 2010 135(5):433-48. 20421371
		Inherited Arrhythmia	LQTS	High prevalence of genetic variants previously associated with LQT syndrome in new exome data. Eur J Hum Genet. 2012 20(8):905-8. doi: 10.1038/ejhg.2012.23. 22378279
		Inherited Arrhythmia	LQTS	LQTS in Northern BC: homozygosity for KCNQ1 V205M presents with a more severe cardiac phenotype but with minimal impact on auditory function. Clin Genet. 2014 86(1):85-90. doi: 10.1111/cge.12235. 23844633
		Inherited Arrhythmia	LQTS	Microscopic mechanisms for long QT syndrome type 1 revealed by single-channel analysis of I(Ks) with S3 domain mutations in KCNQ1. Heart Rhythm. 2015 12(2):386-94. doi: 10.1016/j.hrthm.2014.10.029. 25444851
		Unknown		Actionable exomic incidental findings in 6503 participants: challenges of variant classification. Genome Res. 2015 25(3):305-15. doi: 10.1101/gr.183483.114. 25637381
		Inherited Arrhythmia	LQTS	RNA splicing. The human splicing code reveals new insights into the genetic determinants of disease. Science. 2015 347(6218):1254806. doi: 10.1126/science.1254806. 25525159