KCNQ1 Variant A512P

Summary of observed carriers, functional annotations, and structural context for KCNQ1 A512P. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

24%

2/10 effective observations

Total carriers

0 LQT1 · 0 unaffected

Functional studies

Publications with functional data

A512P has not been reported in gnomAD. This residue resides in a Mild_Hotspot region for LQT1.

Variant features alone are equivalent to phenotyping 2 individuals with LQT1 and 8 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN	PolyPhen-2	BLAST-PSSM	REVEL	Penetrance Density LQT1 (%)
-1.6	0.773	4	0.748	22

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	8	2	–

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 A512P.
Neighbour residue	Distance (Å)	Observed variants
512	0
513	4	T513A, T513S, T513S,
515	5
514	6	I514T,
516	6
511	6	R511Q, R511W,
509	6	H509Q, H509Q, H509R,
510	6	H510R, H510Y,
508	7	E508G,
517	9	I517T,
518	9	R518Q, R518G,
384	9
392	10	W392R, W392R, W392ins
519	10	R519H, R519C,
385	11	E385K,
520	11	M520R,
387	12	P387T,
381	12	C381Y,
383	13
521	14
386	14	N386K, N386K,
391	14	T391A, T391I,
380	14	R380S, R380S, R380G,