KCNH2 Variant F471Y

Summary of observed carriers, functional annotations, and structural context for KCNH2 F471Y. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

24%

90% CI: 6.0% – 47.7%

2/10 effective observations

Total carriers

0

0 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

F471Y has not been reported in gnomAD. This residue resides in a Hotspot region for LQT2.

Variant features alone are equivalent to phenotyping 2 individuals with LQT2 and 8 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT2 (%)
-2.763 0.975 3 0.926 76

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 8 2 –

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 F471Y.
Neighbour residue Distance (Å) Observed variants
471 0 F471X,
470 5 N470D,
493 6 Y493H, Y493C, Y493F, Y493Ins,
468 6 L468F, L468X, L468R,
472 6 R472C, R472X,
490 6 A490T, A490P,
467 6
489 7 I489F, I489I,
469 7
473 7 T473P,
486 8
494 8 F494Del,
498 9
466 9 D466E, D466E,
487 10 G487S, G487R,
491 10 V491I,
492 10 H492Y,
474 10 T474I,
465 10
400 11 I400N,
475 11 Y475C, Y475Del,
501 11 D501N, D501H, D501Y,
464 11 I464X,
485 12 H485X,
398 12 W398L, W398X,
484 12
502 12 M502I, M502I, M502I,
399 12
496 12
488 13 R488C, R488H,
483 13 V483I,
407 13
534 13 R534C,
497 13 W497L, W497X,
499 14
537 14 R537W
505 14 A505V,
401 14
463 14 F463L, F463L, F463L,
402 14 H402R,
495 14 K495X,
410 14 W410X,
500 15 I500Del,