KCNQ1 Variant T444M

Summary of observed carriers, functional annotations, and structural context for KCNQ1 T444M. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

8%

1/14 effective observations

Total carriers

4

0 LQT1 · 4 unaffected

Functional studies

1

Publications with functional data

T444M is present in 4 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 (%)
-2.07 1.0 1 0.684 2

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 – 4 4 0 –
Variant features alone – 15 9 1 –

Totals may differ from individual publications due to duplicate patients removed during curation.

Functional data

Functional assay results from published electrophysiology studies. HM indicates homomeric channels, HT indicates heteromeric channels.

Homomeric channel data

Published electrophysiology measurements (homomeric).
PubMed ID Year Study Type Assay Temperature Cell Type Result

Heteromeric channel data

Published electrophysiology measurements (heteromeric).
PubMed ID Year Study Type Assay Temperature Cell Type Result

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 T444M.
Neighbour residue Distance (Å) Observed variants
444 0 T444M, T444K
443 4
445 4
442 5 H442R,
446 5 D446E, D446E, D446E, D446E, D446N,
441 7 P441S,
447 7 P447H,
440 8
448 8 P448R, P448Q, P448L, P448S,
439 8
449 8 E449K,
438 9
450 9 E450K,
437 10 M437V,
451 10 R451Q, R451W,
436 11
452 11 R452Q, R452W, R452L,
435 11
453 11
434 12 G434R, G434R,
454 12
433 13 P433A,
455 13 H455Y, H455Q, H455Q, H455R,
432 13 T432I, T432A,
456 13 F456L, F456L, F456L,
431 14 V431L, V431L,
457 14
430 14
458 14
429 15 N429S,
459 15 D459N, D459V,