Paralogue Annotation for KCNQ1 residue 199

Residue details

Gene: KCNQ1
Reference Sequences: LRG: LRG_287, Ensembl variant: ENST00000155840 / ENSP00000155840
Amino Acid Position: 199
Reference Amino Acid: S - Serine
Protein Domain: Transmembrane/Linker/Pore

Paralogue Variants mapped to KCNQ1 residue 199

Paralogue	Variant	Associated Disease	Mapping Quality	Consensus	Pubmed
KCNA1	N255D	Hypomagnesemia	Medium	9	19307729, 19903818

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	TEYVVRLWSAGCRSKYVGLWGRLRFARKPI>S<IIDLIVVVASMVVLCVG-------------	216
KCNQ2	VEYFVRIWAAGCCCRYRGWRGRLKFARKPF>C<VIDIMVLIASIAVLAAG-------------	186
KCNQ3	AEFALRIWAAGCCCRYKGWRGRLKFARKPL>C<MLDIFVLIASVPVVAVG-------------	216
KCNQ4	LEYIVRVWSAGCCCRYRGWQGRFRFARKPF>C<VIDFIVFVASVAVIAAG-------------	192
KCNQ5	LEFIIRIWSAGCCCRYRGWQGRLRFARKPF>C<VIDTIVLIASIAVVSAK-------------	220
KCNA1	FELVVR---------FFACPSKTDFFKNIM>N<FIDIVAIIPYFITLGTEIAEQEG-------	278
KCNA10	FELVLR---------FVVCPSKTDFFRNIM>N<IIDIISIIPYFATLITELVQETEP------	329
KCNA2	FEFLVR---------FFACPSKAGFFTNIM>N<IIDIVAIIPYFITLGTELAEKPE-------	279
KCNA3	FELLVR---------FFACPSKATFSRNIM>N<LIDIVAIIPYFITLGTELAERQ--------	351
KCNA4	FEFVVR---------CFACPSQALFFKNIM>N<IIDIVSILPYFITLGTDLAQQQGG------	429
KCNA5	FELLVR---------FFACPSKAGFSRNIM>N<IIDVVAIFPYFITLGTELAEQQ---PGGGG	385
KCNA6	FELLVR---------FSACPSKPAFFRNIM>N<IIDLVAIFPYFITLGTELVQQQEQQPASGG	327
KCNA7	FELLVR---------LLVCPSKAIFFKNVM>N<LIDFVAILPYFVALGTELARQR--------	265
KCNB1	MEYLLR---------FLSSPKKWKFFKGPL>N<AIDLLAILPYYVTIFLTES---N-------	283
KCNB2	MEYLLR---------FLSSPNKWKFFKGPL>N<VIDLLAILPYYVTIFLTES---N-------	287
KCNC1	FEFLMR---------VIFCPNKVEFIKNSL>N<IIDFVAILPFYLEVGLSG------------	297
KCNC2	FEFLVR---------IVFSPNKLEFIKNLL>N<IIDFVAILPFYLEVGLSG------------	334
KCNC3	FEFLMR---------ITFCPDKVEFLKSSL>N<IIDCVAILPFYLEVGLSG------------	400
KCNC4	LEFLVR---------IVCCPDTLDFVKNLL>N<IIDFVAILPFYLEVGLSG------------	333
KCND1	GEYLLR---------LFAAPSRCRFLRSVM>S<LIDVVAILPYYIGLLVP-------------	282
KCND2	VEYLLR---------LAAAPSRYRFVRSVM>S<IIDVVAILPYYIGLVMT-------------	280
KCND3	VEYLLR---------LFAAPSRYRFIRSVM>S<IIDVVAIMPYYIGLVMT-------------	277
KCNF1	LEYLLR---------LFSSPNKLHFALSFM>N<IVDVLAILPFYVSLTLTHL-----------	275
KCNG1	LEFLLR---------LIQAPSKFAFLRSPL>T<LIDLVAILPYYITLLVDGAAAGRR----KP	328
KCNG2	FEFLLR---------SLQAESKCAFLRAPL>N<IIDILALLPFYVSLLLGL-----A----AG	273
KCNG3	AECIVR---------FIVSKNKCEFVKRPL>N<IIDLLAITPYYISVLMTV-----------F	274
KCNG4	LEFCLR---------FVQAQDKCQFFQGPL>N<IIDILAISPYYVSLAVSEEPPEDG----ER	322
KCNS1	FEVSSR---------LLLAPSTRNFFCHPL>N<LIDIVSVLPFYLTLLAGVALG-D-------	328
KCNS2	FELVAR---------FAVAPDFLKFFKNAL>N<LIDLMSIVPFYITLVVNLV---V-------	281
KCNS3	GELAVR---------LAAAPCQKKFWKNPL>N<IIDFVSIIPFYATLAVDTK---E-------	276
KCNV1	GEFVLR---------FLCVRDRCRFLRKVP>N<IIDLLAILPFYITLLVESLSG-S-------	298
KCNV2	LEYLLR---------LASTPDLRRFARSAL>N<LVDLVAILPLYLQLLLECFTGEGH----QR	362
cons	> <

See full Alignment of Paralogues

Known Variants in KCNQ1

Protein	CDS	Disease Classification	Disease	dbSNP links	Effect Prediction
p.S199A	c.595T>G	Inherited Arrhythmia	LQTS	rs199472701	SIFT: deleterious Polyphen: probably damaging
Reports		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