KCNQ1 Variant K422T

Summary of observed carriers, functional annotations, and structural context for KCNQ1 K422T. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

19%

2/13 effective observations

Total carriers

3

1 LQT1 · 2 unaffected

Functional studies

0

Publications with functional data

K422T is present in 2 alleles in gnomAD. This residue resides in a Mild_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 (%)
-1.77 0.23 0 0.687 17

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
30758498 2019 3 None 3 None
23995305 2013 4 None 1 None
Literature, cohort, and gnomAD 3 2 1
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 K422T.
Neighbour residue Distance (Å) Observed variants
422 0 K422T, K422R,
421 4 K421N, K421N,
423 4
420 5 K420E, K420N, K420N,
424 5 K424T,
419 7
425 7 L425V,
418 8 V418I,
426 8
417 8 V417M,
427 8
416 9 V416M,
428 9 D428G,
415 10
429 10 N429S,
414 11
430 11
413 11 K413R,
431 11 V431L, V431L,
412 12 P412S,
432 12 T432I, T432A
411 13
433 13 P433A,
410 13
434 13 G434R, G434R,
409 14
435 14
408 14 P408A,
436 14
407 15
437 15 M437V,