KCNQ1 Variant R401W

Summary of observed carriers, functional annotations, and structural context for KCNQ1 R401W. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

6%

1/30 effective observations

Total carriers

20

0 LQT1 · 20 unaffected

Functional studies

0

Publications with functional data

R401W is present in 20 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 (%)
-2.78 0.999 -3 0.585 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 – 20 20 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 R401W.
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,