KCNQ1 Variant R401Q

Summary of observed carriers, functional annotations, and structural context for KCNQ1 R401Q. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

10%

1/13 effective observations

Total carriers

0 LQT1 · 3 unaffected

Functional studies

Publications with functional data

R401Q is present in 3 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 (%)
-0.43	0.328	1	0.62	9

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	–	3	3	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 R401Q.
Neighbour residue	Distance (Å)	Observed variants
401	0	R401W, R401Q,
400	4
402	4
399	5	A399S, A399V, A399G,
403	5	H403P,
398	7	K398R,
404	7
397	8	R397W, R397Q, R397G,
405	8
396	8
406	8
395	9	Y395C,
407	9
394	10	I394L,
408	10	P408A,
393	11	K393N,
409	11
392	11	W392R, W392R, W392ins
410	11
391	12	T391A, T391I,
411	12
390	13
412	13	P412S,
389	13	S389P,
413	13	K413R,
388	14	D388H, D388N,
414	14
387	14	P387T,
415	14
386	15	N386K, N386K,
416	15	V416M,