KCNQ1 Variant I394L

Summary of observed carriers, functional annotations, and structural context for KCNQ1 I394L. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

17%

1/11 effective observations

Total carriers

1

0 LQT1 · 1 unaffected

Functional studies

0

Publications with functional data

I394L is present in 1 alleles 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 (%)
-1.23 0.031 0 0.595 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 LQT1 Other Disease
Literature, cohort, and gnomAD – 1 1 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 I394L.
Neighbour residue Distance (Å) Observed variants
394 0 I394L,
393 5 K393N,
391 9 T391A, T391I,
392 9 W392R, W392R, W392ins
514 10 I514T,
390 11
518 11 R518Q, R518G,
380 11 R380S, R380S, R380G,
510 12 H510R, H510Y,
389 12 S389P,
511 12 R511Q, R511W,
517 13 I517T,
513 13 T513A, T513S, T513S,
383 14
521 14
384 14
387 14 P387T,
379 15 W379R, W379R, W379C, W379C, W379G,