KCNH2 Variant V476L

Summary of observed carriers, functional annotations, and structural context for KCNH2 V476L. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

18%

1/10 effective observations

Total carriers

0

0 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

V476L has not been reported in gnomAD. This residue resides in a Mild_Hotspot region for LQT2.

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 (%)
-2.713 0.937 1 0.808 31

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 V476L.
Neighbour residue Distance (Å) Observed variants
476 0 V476I,
475 5 Y475C, Y475Del,
477 5
481 6
4 6
482 6 V482A,
480 7 E480V,
478 7 A478D,
6 7 G6R,
483 7 V483I,
402 7 H402R,
474 8 T474I,
5 9
479 9
3 9
492 10 H492Y,
484 11
403 11
489 11 I489F, I489I,
473 11 T473P,
702 11
7 11
401 12
8 12
699 12 E699D, E699D,
488 12 R488C, R488H,
540 12 D540fsX,
703 12
827 12
537 13 R537W,
541 13 R541C, R541H,
538 13
706 13 S706C, S706F,
9 13 A9T, A9V
470 13 N470D,
765 13
493 13 Y493H, Y493C, Y493F, Y493Ins,
407 14
698 14 E698K, E698X,
404 14
491 14 V491I,
400 14 I400N,
497 14 W497L, W497X,
490 14 A490T, A490P,
695 14
485 14 H485X,
496 15
764 15