KCNQ1 Variant D454A

Summary of observed carriers, functional annotations, and structural context for KCNQ1 D454A. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

15%

1/10 effective observations

Total carriers

0

0 LQT1 · 0 unaffected

Functional studies

0

Publications with functional data

D454A has not been reported in gnomAD. This residue resides in a Mild_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 (%)
-1.0 0.051 0 0.608 14

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 D454A.
Neighbour residue Distance (Å) Observed variants
454 0
453 4
455 4 H455Y, H455Q, H455Q, H455R,
452 5 R452Q, R452W, R452L,
456 5 F456L, F456L, F456L,
451 7 R451Q, R451W,
457 7
450 8 E450K,
458 8
449 8 E449K,
459 8 D459N, D459V,
448 9 P448R, P448Q, P448L, P448S,
460 9 G460S, G460D, G460C,
447 10 P447H,
461 10
446 11 D446E, D446E, D446E, D446E, D446N,
462 11 D462N
445 11
463 11 S463T,
444 12 T444M, T444K,
464 12 S464P,
443 13
465 13
442 13 H442R,
466 13
441 14 P441S,
467 14 K467R,
440 14
468 14 S468G, S468N,
439 15
469 15