KCNQ1 Variant F523V

Summary of observed carriers, functional annotations, and structural context for KCNQ1 F523V. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

44%

4/10 effective observations

Total carriers

0 LQT1 · 0 unaffected

Functional studies

Publications with functional data

F523V 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 (%)
-6.04	0.592	-1	0.932	48

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	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 F523V.
Neighbour residue	Distance (Å)	Observed variants
523	0
522	5	Y522S,
519	6	R519H, R519C,
524	6	V524G,
526	6	K526Q, K526E,
520	6	M520R,
525	7	A525T, A525V,
521	8
527	9
377	9
381	9	C381Y,
516	9
374	9	L374H, L374F,
517	10	I517T,
378	10	A378T,
528	10
518	11	R518Q, R518G,
530	11
515	11
373	11	S373P,
380	12	R380S, R380S, R380G,
529	12
375	13
376	13
370	13	A370V,
514	14	I514T,
371	14	A371T,
384	14
372	14
531	15
513	15	T513A, T513S, T513S