KCNQ1 Variant D428G

Summary of observed carriers, functional annotations, and structural context for KCNQ1 D428G. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

1/11 effective observations

Total carriers

0 LQT1 · 1 unaffected

Functional studies

Publications with functional data

D428G has not been reported in gnomAD. This residue resides in a Non_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 (%)
-1.25	0.012	-2	0.569	2

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
22949429	2012	1	1	None	None
19841300	2009	1	1	None	None
Literature, cohort, and gnomAD	–	1	1	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 D428G.
Neighbour residue	Distance (Å)	Observed variants
428	0	D428G,
427	4
429	4	N429S,
426	5
430	5
425	7	L425V,
431	7	V431L, V431L,
424	8	K424T,
432	8	T432I, T432A
423	8
433	8	P433A,
422	9	K422T, K422R,
434	9	G434R, G434R,
421	10	K421N, K421N,
435	10
420	11	K420E, K420N, K420N,
436	11
419	11
437	11	M437V,
418	12	V418I,
438	12
417	13	V417M,
439	13
416	13	V416M,
440	13
415	14
441	14	P441S,
414	14
442	14	H442R,
413	15	K413R,
443	15