KCNQ1 Variant F423C

Summary of observed carriers, functional annotations, and structural context for KCNQ1 F423C. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

19%

1/10 effective observations

Total carriers

0 LQT1 · 0 unaffected

Functional studies

Publications with functional data

F423C has not been reported 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 (%)
-1.13	0.001	2	0.725	13

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	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 F423C.
Neighbour residue	Distance (Å)	Observed variants
423	0
422	4	K422T, K422R,
424	4	K424T,
421	5	K421N, K421N,
425	5	L425V,
420	7	K420E, K420N, K420N,
426	7
419	8
427	8
418	8	V418I,
428	8	D428G,
417	9	V417M,
429	9	N429S,
416	10	V416M,
430	10
415	11
431	11	V431L, V431L,
414	11
432	11	T432I, T432A
413	12	K413R,
433	12	P433A,
412	13	P412S,
434	13	G434R, G434R,
411	13
435	13
410	14
436	14
409	14
437	14	M437V,
408	15	P408A,
438	15