Paralogue Annotation for KCNH2 residue 631

Residue details

Gene: KCNH2
Reference Sequences: LRG: LRG_288, Ensembl variant: ENST00000262186 / ENSP00000262186
Amino Acid Position: 631
Reference Amino Acid: S - Serine
Protein Domain: Transmembrane/Linker/Pore

Paralogue Variants mapped to KCNH2 residue 631

Paralogue	Variant	Associated Disease	Mapping Quality	Consensus	Pubmed
HCN4	A485V	Sinus bradycardia	Medium	9	20662977, 24569893

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	-LGGPSIKDKYVTALYFTFSSLTSVGFGNV>S<PNTNSEKIFSICVMLIGSLMYASIFGNVSA	661
KCNH1	WEGGPSKNSVYISSLYFTMTSLTSVGFGNI>A<PSTDIEKIFAVAIMMIGSLLYATIFGNVTT	500
KCNH3	LLGGPSLRSAYITSLYFALSSLTSVGFGNV>S<ANTDTEKIFSICTMLIGALMHAVVFGNVTA	502
KCNH4	SVGGPSRRSAYIAALYFTLSSLTSVGFGNV>C<ANTDAEKIFSICTMLIGALMHAVVFGNVTA	476
KCNH5	WEGGPSKDSLYVSSLYFTMTSLTTIGFGNI>A<PTTDVEKMFSVAMMMVGSLLYATIFGNVTT	469
KCNH6	-ASGPSVQDKYVTALYFTFSSLTSVGFGNV>S<PNTNSEKVFSICVMLIGSLMYASIFGNVSA	513
KCNH7	-SSGPSIKDKYVTALYFTFSSLTSVGFGNV>S<PNTNSEKIFSICVMLIGSLMYASIFGNVSA	664
KCNH8	TLGGPSIRSAYIAALYFTLSSLTSVGFGNV>S<ANTDAEKIFSICTMLIGALMHALVFGNVTA	471
CNGA1	--EFGRLARKYVYSLYWSTLTLTTIG-ETP>P<PVRDSEYVFVVVDFLIGVLIFATIVGNIGS	398
CNGA2	--EYGYLAREYIYCLYWSTLTLTTIG-ETP>P<PVKDEEYLFVIFDFLIGVLIFATIVGNVGS	373
CNGA3	--EHGRLSRKYIYSLYWSTLTLTTIG-ETP>P<PVKDEEYLFVVVDFLVGVLIFATIVGNVGS	401
CNGA4	--GFERLRRQYLYSFYFSTLILTTVG-DTP>P<PAREEEYLFMVGDFLLAVMGFATIMGSMSS	267
CNGB1	-----GVGNSYIRCYYFAVKTLITIG-GLP>D<PKTLFEIVFQLLNYFTGVFAFSVMIGQMRD	881
CNGB3	-----GEGNEYLRCYYWAVRTLITIG-GLP>E<PQTLFEIVFQLLNFFSGVFVFSSLIGQMRD	443
HCN1	--VNDSWGKQYSYALFKAMSHMLCIGYGAQ>A<PVSMSDLWITMLSMIVGATCYAMFVGHATA	395
HCN2	--VNHSWSELYSFALFKAMSHMLCIGYGRQ>A<PESMTDIWLTMLSMIVGATCYAMFIGHATA	464
HCN3	--VNHSWGRQYSHALFKAMSHMLCIGYGQQ>A<PVGMPDVWLTMLSMIVGATCYAMFIGHATA	348
HCN4	--VNNSWGKQYSYALFKAMSHMLCIGYGRQ>A<PVGMSDVWLTMLSMIVGATCYAMFIGHATA	515
cons	> <

See full Alignment of Paralogues

Known Variants in KCNH2

Protein	CDS	Disease Classification	Disease	dbSNP links	Effect Prediction
p.S631A	c.1891T>G	Inherited Arrhythmia	LQTS	rs199472959	SIFT: tolerated Polyphen: possibly damaging
Reports		Inherited Arrhythmia	LQTS	Voltage-gated ion channels and hereditary disease. Physiol Rev. 1999 79(4):1317-72. 10508236
		Inherited Arrhythmia	LQTS	Molecular determinants for activation and inactivation of HERG, a human inward rectifier potassium channel. J Physiol. 1996 493 ( Pt 3):635-42. 8799887