KCNQ1 Variant C381W

Summary of observed carriers, functional annotations, and structural context for KCNQ1 C381W. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

26%

2/10 effective observations

Total carriers

0

0 LQT1 · 0 unaffected

Functional studies

1

Publications with functional data

C381W has not been reported 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 (%)
-9.95 0.999 -2 0.798 30

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 8 2 –

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 C381W.
Neighbour residue Distance (Å) Observed variants
381 0 C381Y,
378 5 A378T,
518 5 R518Q, R518G,
384 6
377 6
383 6
380 6 R380S, R380S, R380G,
519 7 R519H, R519C,
522 7 Y522S,
382 7
515 7
379 7 W379R, W379R, W379C, W379C, W379G,
385 8 E385K,
521 9
523 9
516 9
517 10 I517T,
391 10 T391A, T391I,
514 10 I514T,
374 10 L374H, L374F,
376 10
392 10 W392R, W392R, W392ins
520 11 M520R,
375 11
386 11 N386K, N386K,
525 12 A525T, A525V,
389 12 S389P,
373 12 S373P,
512 12
526 12 K526Q, K526E,
387 12 P387T,
524 13 V524G,
513 13 T513A, T513S, T513S,
511 13 R511Q, R511W,
390 14
372 14
371 15 A371T,