KCNQ1 Variant E449K

Summary of observed carriers, functional annotations, and structural context for KCNQ1 E449K. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

7%

1/17 effective observations

Total carriers

7

0 LQT1 · 7 unaffected

Functional studies

1

Publications with functional data

E449K is present in 7 alleles 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 (%)
-1.07 0.013 -2 0.624 6

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 – 7 7 0 –
Variant features alone – 15 9 1 –

Totals may differ from individual publications due to duplicate patients removed during curation.

Functional data

Functional assay results from published electrophysiology studies. HM indicates homomeric channels, HT indicates heteromeric channels.

Homomeric channel data

Published electrophysiology measurements (homomeric).
PubMed ID Year Study Type Assay Temperature Cell Type Result

Heteromeric channel data

Published electrophysiology measurements (heteromeric).
PubMed ID Year Study Type Assay Temperature Cell Type Result

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 E449K.
Neighbour residue Distance (Å) Observed variants
449 0 E449K,
448 4 P448R, P448Q, P448L, P448S,
450 4 E450K,
447 5 P447H,
451 5 R451Q, R451W,
446 7 D446E, D446E, D446E, D446E, D446N,
452 7 R452Q, R452W, R452L,
445 8
453 8
444 8 T444M, T444K,
454 8
443 9
455 9 H455Y, H455Q, H455Q, H455R,
442 10 H442R,
456 10 F456L, F456L, F456L,
441 11 P441S,
457 11
440 11
458 11
439 12
459 12 D459N, D459V,
438 13
460 13 G460S, G460D, G460C,
437 13 M437V,
461 13
436 14
462 14 D462N
435 14
463 14 S463T,
434 15 G434R, G434R,
464 15 S464P,