KCNQ1 Variant D459H

Summary of observed carriers, functional annotations, and structural context for KCNQ1 D459H. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

12%

1/10 effective observations

Total carriers

0

0 LQT1 · 0 unaffected

Functional studies

0

Publications with functional data

D459H has not been reported in gnomAD. This residue resides in a Non_Hotspot region for LQT1.

Variant features alone are equivalent to phenotyping 1 individuals with LQT1 and 9 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT1 (%)
-2.23 0.989 0 0.66 2

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 LQT1 Other Disease
Literature, cohort, and gnomAD – 0 0 0 –
Variant features alone – 15 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.

Previously observed variants near D459H.
Neighbour residue Distance (Å) Observed variants
459 0 D459N, D459V,
458 4
460 4 G460S, G460D, G460C,
457 5
461 5
456 7 F456L, F456L, F456L,
462 7 D462N
455 8 H455Y, H455Q, H455Q, H455R,
463 8 S463T,
454 8
464 8 S464P,
453 9
465 9
452 10 R452Q, R452W, R452L,
466 10
451 11 R451Q, R451W,
467 11 K467R,
450 11 E450K,
468 11 S468G, S468N,
449 12 E449K,
469 12
448 13 P448R, P448Q, P448L, P448S,
470 13
447 13 P447H,
471 13
446 14 D446E, D446E, D446E, D446E, D446N,
472 14 L472P,
445 14
473 14 E473Q,
444 15 T444M, T444K,
474 15