Paralogue Annotation for KCNH2 residue 141

Residue details

Gene: KCNH2
Reference Sequences: LRG: LRG_288, Ensembl variant: ENST00000262186 / ENSP00000262186
Amino Acid Position: 141
Reference Amino Acid: P - Proline
Protein Domain: N-terminus

Paralogue Variants mapped to KCNH2 residue 141

Paralogue	Variant	Associated Disease	Mapping Quality	Consensus	Pubmed
CNGA3	P95L	Progressive cone dystrophy ?	Medium	2	20079539

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	-----------------------------S>P<AHD---------------------------	144
KCNH1	-----------------------------E>D<DS----------------------------	144
KCNH3	-----------------------------G>P<DR----------------------------	144
KCNH4	-----------------------------G>P<QG----------------------------	145
KCNH5	-----------------------------E>D<DS----------------------------	142
KCNH6	------------------------------>-<------------------------------
KCNH7	-----------------------------T>P<ERV---------------------------	144
KCNH8	-----------------------------T>P<E-----------------------------	143
CNGA1	-----------------------------E>P<EE----------------------------	104
CNGA2	-----------------------------R>P<DS----------------------------	93
CNGA3	-----------------------------G>P<DS----------------------------	97
CNGA4	------------------------------>-<------------------------------
CNGB1	EDAHQDVSTSPQGTEVVPAYEEENKAVEKM>P<RELSRIEEEKEDEEEEEEEEEEEEEEEVTE	374
CNGB3	-----------------------------M>F<KSLTKVNKVKPIGENNENEQS---------	23
HCN1	-----------------------------G>G<EE----------------------------	76
HCN2	-----------------------------G>P<AE----------------------------	142
HCN3	------------------------------>-<------------------------------
HCN4	-----------------------------E>G<GA----------------------------	194
cons	> <

See full Alignment of Paralogues

Known Variants in KCNH2

Protein	CDS	Disease Classification	Disease	dbSNP links	Effect Prediction
p.P141L	c.422C>T	Inherited Arrhythmia	LQTS	rs199472864	SIFT: deleterious Polyphen: benign
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
		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	Identification of Medically Actionable Secondary Findings in the 1000 Genomes. PLoS One. 2015 10(9):e0135193. doi: 10.1371/journal.pone.0135193. 26332594