Paralogue Annotation for KCNH2 residue 774

Residue details

Gene: KCNH2
Reference Sequences: LRG: LRG_288, Ensembl variant: ENST00000262186 / ENSP00000262186
Amino Acid Position: 774
Reference Amino Acid: D - Aspartate
Protein Domain: C-terminus

Paralogue Variants mapped to KCNH2 residue 774

Paralogue	Variant	Associated Disease	Mapping Quality	Consensus	Pubmed
CNGA3	D514V	Achromatopsia	High	9	21778272

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 KCNH2.

KCNH2	RGATKGCLRALAMKFKTTHAPPGDTLVHAG>D<LLTALYFISRGSIEILRG-D--V--VVAIL	799
KCNH1	RLASDGCLRALAMEFQTVHCAPGDLIYHAG>E<SVDSLCFVVSGSLEVIQD-D--E--VVAIL	638
KCNH3	EAASRGCLRALSLALRPAFCTPGEYLIHQG>D<ALQALYFVCSGSMEVLKG-G--T--VLAIL	639
KCNH4	GAASRGCLRALSLHIKTSFCAPGEYLLRRG>D<ALQAHYYVCSGSLEVLRD-N--M--VLAIL	613
KCNH5	RLASDGCLRALAVEFQTIHCAPGDLIYHAG>E<SVDALCFVVSGSLEVIQD-D--E--VVAIL	607
KCNH6	SGAGKGCLRALAVKFKTTHAPPGDTLVHLG>D<VLSTLYFISRGSIEILRD-D--V--VVAIL	651
KCNH7	RGASKGCLRALAMKFKTTHAPPGDTLVHCG>D<VLTALYFLSRGSIEILKD-D--I--VVAIL	802
KCNH8	ECASRGCLRSLSLHIKTSFCAPGEYLLRQG>D<ALQAIYFVCSGSMEVLKD-S--M--VLAIL	608
CNGA1	ADCEAGLLVELVLKLQPQVYSPGDYICKKG>D<IGREMYIIKEGKLAVVAD-D--GVTQFVVL	538
CNGA2	HDCEAGLLVELVLKLRPQVFSPGDYICRKG>D<IGKEMYIIKEGKLAVVAD-D--GVTQYALL	513
CNGA3	QDCEAGLLVELVLKLRPTVFSPGDYICKKG>D<IGKEMYIINEGKLAVVAD-D--GVTQFVVL	541
CNGA4	QNCEASLLEELVLKLQPQTYSPGEYVCRKG>D<IGQEMYIIREGQLAVVAD-D--GITQYAVL	407
CNGB1	QGCDRQMIFDMLKRLRSVVYLPNDYVCKKG>E<IGREMYIIQAGQVQVLGGPDGKS--VLVTL	1022
CNGB3	KGCDTQMIYDMLLRLKSVLYLPGDFVCKKG>E<IGKEMYIIKHGEVQVLGGPDGTK--VLVTL	584
HCN1	ANADPNFVTAMLSKLRFEVFQPGDYIIREG>A<VGKKMYFIQHGVAGVITK-S--S--KEMKL	532
HCN2	ANADPNFVTAMLTKLKFEVFQPGDYIIREG>T<IGKKMYFIQHGVVSVLTK-G--N--KEMKL	601
HCN3	AHADPSFVTAVLTKLRFEVFQPGDLVVREG>S<VGRKMYFIQHGLLSVLAR-G--A--RDTRL	485
HCN4	ANADPNFVTSMLTKLRFEVFQPGDYIIREG>T<IGKKMYFIQHGVVSVLTK-G--N--KETKL	652
cons	> <

See full Alignment of Paralogues

Known Variants in KCNH2

Protein	CDS	Disease Classification	Disease	dbSNP links	Effect Prediction
p.D774Y	c.2320G>T	Inherited Arrhythmia	LQTS	rs199472995	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	Long QT and Brugada syndrome gene mutations in New Zealand. Heart Rhythm. 2007 4(10):1306-14. 17905336
		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
		Inherited Arrhythmia	LQTS	End-recovery QTc: a useful metric for assessing genetic variants of unknown significance in long-QT syndrome. J Cardiovasc Electrophysiol. 2012 23(6):637-42. doi: 10.1111/j.1540-8167.2011.02265. 22429796
		Inherited Arrhythmia	LQTS	Large-scale mutational analysis of Kv11.1 reveals molecular insights into type 2 long QT syndrome. Nat Commun. 2014 5:5535. doi: 10.1038/ncomms6535. 25417810