KCNH2 Variant F551Y

Summary of observed carriers, functional annotations, and structural context for KCNH2 F551Y. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

13%

1/10 effective observations

Total carriers

0

0 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

F551Y has not been reported in gnomAD. This residue resides in a Non_Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 0% of WT with a standard error of 29%. In our analysis we used SE < 20% as 'high quality'. Approximately below 50% of WT is considered PS3 moderate and below 30% is PS3 strong.

Variant features alone are equivalent to phenotyping 1 individuals with LQT2 and 9 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT2 (%)
-2.412 0.236 2 0.737 4

PROVEAN scores below -2 suggest deleterious impact. REVEL scores above 0.5–0.75 are often interpreted as likely pathogenic. PolyPhen-2 scores above 0.85 are typically pathogenic. BLAST-PSSM reflects evolutionary conservation; more negative values indicate rarer substitutions. Penetrance density summarises neighbouring residue risk (Kroncke et al. 2019).

Reported carrier data

Observed carriers by publication or cohort.
Source Year Carriers Unaffected LQT2 Other Disease
Literature, cohort, and gnomAD – 0 0 0 –
Variant features alone – 10 9 1 –

Totals may differ from individual publications due to duplicate patients removed during curation.

Nearby variants

Neighbouring residues within 15 Ångström provide structural context. Variants listed in the right-most column have been observed clinically or in gnomAD. Note that some residues appear multiple times at different distances since the functional KV11.1 channel (protein product of KCNH2/hERG) is a homotetramer and occasionally the same residue from multiple subunits is present within the 15Å window.

Previously observed variants near F551Y.
Neighbour residue Distance (Å) Observed variants
551 0 F551L, F551L, F551L,
552 5 L552S,
555 5
548 6
550 6
554 7
549 7 V549M,
553 7 L553V,
547 8 A547T,
556 8
415 9
419 10
412 10 W412X,
546 10
416 10
542 10
558 11 A558P, A558E, A558V,
559 11 L559F, L559H,
557 11
545 12
659 12
543 12 S543fsX,
662 12
535 12 V535M,
418 13
655 13
646 13
650 13 L650X,
539 13
656 13 F656L, F656L, F656L
413 14 L413P,
544 14 E544A, E544fsX,
658 14
560 14 I560fsX, I560M,
663 14
414 14 I414fsX,
422 14 A422T,
417 14
532 14
423 14
666 14
411 15
647 15
541 15 R541C, R541H,
649 15