KCNQ1 Variant A525V

Summary of observed carriers, functional annotations, and structural context for KCNQ1 A525V. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

55%

9/17 effective observations

Total carriers

7

5 LQT1 · 2 unaffected

Functional studies

0

Publications with functional data

A525V has not been reported in gnomAD. This residue resides in a Hotspot region for LQT1.

Variant features alone are equivalent to phenotyping 4 individuals with LQT1 and 6 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT1 (%)
-3.51 0.927 -1 0.936 52

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
32893267 2020 5 None 5 None
30758498 2019 13 None 6 None
29688407 2018 2 2 None None
19716085 2009 1 None 1 None
Literature, cohort, and gnomAD 7 2 5
Variant features alone 15 6 4

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 A525V.
Neighbour residue Distance (Å) Observed variants
525 0 A525T, A525V,
524 4 V524G,
528 5
374 5 L374H, L374F,
373 5 S373P,
526 5 K526Q, K526E,
522 6 Y522S,
370 6 A370V,
527 7
377 7
529 7
523 7
521 8
371 8 A371T,
530 8
372 8
376 9
375 9
378 9 A378T,
369 10
532 10
520 10 M520R,
531 10
380 11 R380S, R380S, R380G,
519 12 R519H, R519C,
381 12 C381Y,
533 12 R533W, R533Q,
367 12 Q367H, Q367H,
518 13 R518Q, R518G,
368 13
517 13 I517T,
534 13
543 14 E543K,
379 14 W379R, W379R, W379C, W379C, W379G
547 14 Q547R,
516 15