KCNQ1 Variant V524G

Summary of observed carriers, functional annotations, and structural context for KCNQ1 V524G. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

79%

12/16 effective observations

Total carriers

6

6 LQT1 · 0 unaffected

Functional studies

0

Publications with functional data

V524G has not been reported in gnomAD. This residue resides in a Hotspot region for LQT1.

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

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT1 (%)
-6.0 0.992 -1 0.941 76

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 6 None 6 None
22949429 2012 6 None 6 None
21964171 2011 1 None None Drowning
19841300 2009 6 None 6 None
19716085 2009 1 None 1 None
17470695 2007 4 None 4 None
14678125 2003 1 None 1 None
Literature, cohort, and gnomAD 6 0 6
Variant features alone 15 4 6

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 V524G.
Neighbour residue Distance (Å) Observed variants
524 0 V524G,
525 4 A525T, A525V,
528 5
527 6
523 6
521 6
526 7 K526Q, K526E,
522 7 Y522S,
520 8 M520R,
373 8 S373P,
374 9 L374H, L374F,
377 9
530 10
370 10 A370V,
529 10
519 11 R519H, R519C,
517 11 I517T,
531 11
371 12 A371T,
543 12 E543K,
378 12 A378T,
376 12
372 12
380 12 R380S, R380S, R380G,
547 12 Q547R,
532 12
518 12 R518Q, R518G,
381 13 C381Y,
516 13
369 13
375 13
534 14
533 15 R533W, R533Q,
546 15 S546L, S546W