KCNH2 Variant Y475N

Summary of observed carriers, functional annotations, and structural context for KCNH2 Y475N. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

30%

3/10 effective observations

Total carriers

0

0 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

Y475N has not been reported in gnomAD. This residue resides in a Hotspot region for LQT2.

Variant features alone are equivalent to phenotyping 3 individuals with LQT2 and 7 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT2 (%)
-8.315 0.999 -2 0.943 81

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 7 3 –

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 Y475N.
Neighbour residue Distance (Å) Observed variants
475 0 Y475C, Y475Del,
483 5 V483I,
476 5 V476I,
474 5 T474I,
477 6
489 6 I489F, I489I,
492 6 H492Y,
482 7 V482A,
484 8
473 8 T473P,
480 8 E480V,
402 8 H402R,
481 8
488 9 R488C, R488H,
478 9 A478D,
490 10 A490T, A490P,
493 10 Y493H, Y493C, Y493F, Y493Ins,
491 10 V491I,
470 10 N470D,
6 10 G6R,
4 11
487 11 G487S, G487R,
485 11 H485X,
401 11
471 11 F471X,
479 11
486 11
400 12 I400N,
537 12 R537W,
403 12
472 12 R472C, R472X,
496 12
5 12
497 13 W497L, W497X,
494 13 F494Del,
3 13
407 13
469 13
538 13
399 13
8 13
495 14 K495X,
9 14 A9T, A9V
404 14
498 14
7 14
541 15 R541C, R541H,