KCNQ1 Variant A378S

Summary of observed carriers, functional annotations, and structural context for KCNQ1 A378S. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

31%

3/10 effective observations

Total carriers

0

0 LQT1 · 0 unaffected

Functional studies

0

Publications with functional data

A378S has not been reported in gnomAD. This residue resides in a Mild_Hotspot region for LQT1.

Variant features alone are equivalent to phenotyping 3 individuals with LQT1 and 7 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT1 (%)
-1.04 0.647 1 0.53 36

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 7 3 –

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 A378S.
Neighbour residue Distance (Å) Observed variants
378 0 A378T,
377 4
381 5 C381Y,
522 6 Y522S,
375 6
379 6 W379R, W379R, W379C, W379C, W379G,
374 6 L374H, L374F,
380 6 R380S, R380S, R380G,
376 7
382 7
383 8
373 9 S373P,
518 9 R518Q, R518G,
525 9 A525T, A525V,
521 10
372 10
384 10
519 10 R519H, R519C,
523 10
526 10 K526Q, K526E,
371 11 A371T,
385 11 E385K,
391 11 T391A, T391I,
515 12
524 12 V524G,
370 12 A370V,
529 12
520 13 M520R,
517 13 I517T,
386 13 N386K, N386K,
516 13
392 14 W392R, W392R, W392ins
389 14 S389P,
514 14 I514T,
528 14
390 15
369 15
530 15