Paralogue Annotation for KCNQ1 residue 520

Residue details

Gene: KCNQ1
Reference Sequences: LRG: LRG_287, Ensembl variant: ENST00000155840 / ENSP00000155840
Amino Acid Position: 520
Reference Amino Acid: M - Methionine
Protein Domain: C-terminus


Paralogue Variants mapped to KCNQ1 residue 520

ParalogueVariantAssociated DiseaseMapping QualityConsensusPubmed
KCNQ2M546VEpileptic encephalopathy, neonatalMedium2 22275249, 24318194

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.



KCNQ1LREHHRATIKV----------------IRR>M<Q----------YFVAKKKFQQARKPYDVRD540
KCNQ2LTPGLKVSIRA----------------VCV>M<R----------FLVSKRKFKESLRPYDVMD566
KCNQ3MIPTLKAAIRA----------------VRI>L<Q----------FRLYKKKFKETLRPYDVKD545
KCNQ4IMPAVKTVIRS----------------IRI>L<K----------FLVAKRKFKETLRPYDVKD560
KCNQ5LTPPLKTVIRA----------------IRI>M<K----------FHVAKRKFKETLRPYDVKD548
KCNA1TTAN--QNCVN----------------KSK>L<L----------TD-----------------494
KCNA10----------G----------------CST>E<K----------SR-----------------510
KCNA2TLAN--TNYVN----------------ITK>M<L----------TD-----------------498
KCNA3TTNNNPNSCVN----------------IKK>I<F----------TD-----------------574
KCNA4ETDK--NNCSN----------------AKA>V<E----------TD-----------------652
KCNA5---------------------------LRR>S<LYALCLDTSRETD-----------------612
KCNA6P-----HRAYA----------------EKR>M<L----------TE-----------------528
KCNA7------LWAPP----------------GKH>L<V----------TE-----------------455
KCNB1KTNNPLKLRAL----------------KVN>F<M----------EG-------DPSPLLPVLG689
KCNB2KGSNPLKSRSL----------------KVN>F<K----------ENRGSAPQTPPSTARPLPV739
KCNC1RSGTRERY--G----------------P-C>F<L----------LSTGEYACPPGGGMRK---564
KCNC2RSSTRDKNRRG----------------ETC>F<L----------LTTGDYTCASDGGIRKG--594
KCNC3-PGSRGRYSRD----------------RAC>F<L----------LT--DYAPSPDGSIRKATG726
KCNC4RSTTRDRNKKA----------------AAC>F<L----------LSTGDYACA-DGSVRKG--607
KCND1LLSSCCPRRAKRRAIRLANSTASVS-RGSM>Q<E----------LDMLA--GLRRSHAPQSRS575
KCND2VTSTCCSRRHKK-TFRIPNANVSGSHQGSI>Q<E----------LSTIQIRCVERTPLSNSRS574
KCND3LTTTCCSRRSKK-TTHLPNSNLPATRLRSM>Q<E----------LSTIHIQGSEQPSLTTSRS591
KCNF1------------------------------>-<------------------------------
KCNG1------------------------------>-<------------------------------
KCNG2------------------------------>-<------------------------------
KCNG3------------------------------>-<------------------------------
KCNG4------------------------------>-<------------------------------
KCNS1------------------------------>-<------------------------------
KCNS2------------------------------>-<------------------------------
KCNS3------------------------------>-<------------------------------
KCNV1------------------------------>-<------------------------------
KCNV2------------------------------>-<------------------------------
cons                              > <                              

See full Alignment of Paralogues


Known Variants in KCNQ1

ProteinCDSDisease ClassificationDiseasedbSNP linksEffect Prediction
p.M520Rc.1559T>G Inherited ArrhythmiaLQTSrs199473479SIFT: deleterious
Polyphen: probably damaging
ReportsInherited ArrhythmiaLQTS The novel C-terminal KCNQ1 mutation M520R alters protein trafficking. Biochem Biophys Res Commun. 2007 358(1):304-10. 17482572
Inherited ArrhythmiaLQTS 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
Inherited ArrhythmiaLQTS Genetic testing for long-QT syndrome: distinguishing pathogenic mutations from benign variants. Circulation. 2009 120(18):1752-60. 19841300
Inherited ArrhythmiaLQTS Clinical aspects of type-1 long-QT syndrome by location, coding type, and biophysical function of mutations involving the KCNQ1 gene. Circulation. 2007 115(19):2481-9. 17470695
Inherited ArrhythmiaLQTS 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