KCNQ1 Variant A399V

Summary of observed carriers, functional annotations, and structural context for KCNQ1 A399V. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

1/20 effective observations

Total carriers

0 LQT1 · 10 unaffected

Functional studies

Publications with functional data

A399V is present in 10 alleles 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 (%)
-0.45	0.002	-2	0.549	10

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	–	10	10	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 A399V.
Neighbour residue	Distance (Å)	Observed variants
399	0	A399S, A399V, A399G,
398	4	K398R,
400	4
397	5	R397W, R397Q, R397G,
401	5	R401W, R401Q,
396	7
402	7
395	8	Y395C,
403	8	H403P,
394	8	I394L,
404	8
393	9	K393N,
405	9
392	10	W392R, W392R, W392ins
406	10
391	11	T391A, T391I,
407	11
390	11
408	11	P408A,
389	12	S389P,
409	12
388	13	D388H, D388N,
410	13
387	13	P387T,
411	13
386	14	N386K, N386K,
412	14	P412S,
385	14	E385K,
413	14	K413R,
384	15
414	15