KCNH2 Variant R472S

Summary of observed carriers, functional annotations, and structural context for KCNH2 R472S. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

14%

1/10 effective observations

Total carriers

0

0 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

R472S 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 (%)
-5.56 0.973 -1 0.92 21

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 R472S.
Neighbour residue Distance (Å) Observed variants
472 0 R472C, R472X,
398 6 W398L, W398X,
471 6 F471X,
486 6
473 6 T473P,
399 7
400 7 I400N,
469 7
468 8 L468F, L468X, L468R,
485 8 H485X,
489 8 I489F, I489I,
470 9 N470D,
474 9 T474I,
484 10
490 10 A490T, A490P,
487 10 G487S, G487R,
401 11
467 11
493 11 Y493H, Y493C, Y493F, Y493Ins,
465 12
466 12 D466E, D466E,
483 12 V483I,
475 12 Y475C, Y475Del,
488 12 R488C, R488H,
407 13
406 13
402 13 H402R,
491 14 V491I,
494 14 F494Del
492 14 H492Y,
404 14
464 14 I464X,
498 15
410 15 W410X,