KCNQ1 Variant E385K

Summary of observed carriers, functional annotations, and structural context for KCNQ1 E385K. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

27%

4/16 effective observations

Total carriers

6

2 LQT1 · 4 unaffected

Functional studies

0

Publications with functional data

E385K is present in 3 alleles in gnomAD. This residue resides in a Mild_Hotspot region for LQT1.

Variant features alone are equivalent to phenotyping 2 individuals with LQT1 and 8 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT1 (%)
-3.08 0.955 0 0.89 34

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
22429796 2012 2 1 1 None
19716085 2009 1 None 1 None
Literature, cohort, and gnomAD – 6 4 2 –
Variant features alone – 15 8 2 –

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 E385K.
Neighbour residue Distance (Å) Observed variants
385 0 E385K,
384 4
383 6
386 6 N386K, N386K,
382 7
515 7
387 7 P387T,
381 8 C381Y,
392 9 W392R, W392R, W392ins
389 10 S389P,
518 10 R518Q, R518G,
388 11 D388H, D388N,
379 11 W379R, W379R, W379C, W379C, W379G,
511 11 R511Q, R511W,
391 11 T391A, T391I,
519 11 R519H, R519C,
512 11
378 11 A378T,
514 12 I514T,
380 12 R380S, R380S, R380G,
516 12
508 13 E508G,
390 13
377 13
522 14 Y522S,
513 14 T513A, T513S, T513S,
517 14 I517T,
510 14 H510R, H510Y,