KCNH2 Variant T474A

Summary of observed carriers, functional annotations, and structural context for KCNH2 T474A. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

24%

2/10 effective observations

Total carriers

0

0 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

T474A 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 (%)
-4.633 0.987 0 0.913 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 T474A.
Neighbour residue Distance (Å) Observed variants
474 0 T474I,
473 4 T473P,
402 5 H402R,
475 5 Y475C, Y475Del,
401 6
483 6 V483I,
484 6
400 7 I400N,
489 7 I489F, I489I,
482 8 V482A,
476 8 V476I,
403 8
399 9
470 9 N470D,
407 9
472 9 R472C, R472X,
485 9 H485X,
404 10
469 10
481 10
471 10 F471X,
486 10
6 11 G6R,
492 11 H492Y,
477 11
488 11 R488C, R488H,
5 11
480 11 E480V,
493 11 Y493H, Y493C, Y493F, Y493Ins,
490 12 A490T, A490P,
398 12 W398L, W398X,
3 12
4 12
487 12 G487S, G487R,
406 12
8 13
408 13
541 13 R541C, R541H,
538 13
405 13
466 13 D466E, D466E,
411 13
491 13 V491I,
537 13 R537W,
468 14 L468F, L468X, L468R,
478 14 A478D,
410 14 W410X,
7 14
467 14
9 14 A9T, A9V