KCNQ1 Variant K526Q

Summary of observed carriers, functional annotations, and structural context for KCNQ1 K526Q. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

13%

1/14 effective observations

Total carriers

4

0 LQT1 · 4 unaffected

Functional studies

0

Publications with functional data

K526Q is present in 4 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 (%)
-1.66 0.943 0 0.879 16

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 – 4 4 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 K526Q.
Neighbour residue Distance (Å) Observed variants
526 0 K526Q, K526E,
525 5 A525T, A525V,
530 5
522 6 Y522S,
523 6
527 6
374 7 L374H, L374F,
529 7
524 7 V524G,
528 8
377 10
373 10 S373P,
370 10 A370V,
371 10 A371T,
531 10
378 10 A378T,
533 10 R533W, R533Q,
532 11
375 11
521 11
519 11 R519H, R519C,
534 12
520 12 M520R,
372 12
381 12 C381Y,
376 13
367 13 Q367H, Q367H,
369 14
380 14 R380S, R380S, R380G
518 15 R518Q, R518G,