KCNQ1 Variant H455Y

Summary of observed carriers, functional annotations, and structural context for KCNQ1 H455Y. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

30%

4/15 effective observations

Total carriers

5

3 LQT1 · 2 unaffected

Functional studies

1

Publications with functional data

H455Y has not been reported 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 (%)
-1.52 0.159 -3 0.586 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
29672598 2018 1 1 None None
19808498 2009 1 None 1 None
Literature, cohort, and gnomAD – 5 2 3 –
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 H455Y.
Neighbour residue Distance (Å) Observed variants
455 0 H455Y, H455Q, H455Q, H455R,
454 4
456 4 F456L, F456L, F456L,
453 5
457 5
452 7 R452Q, R452W, R452L,
458 7
451 8 R451Q, R451W,
459 8 D459N, D459V,
450 8 E450K,
460 8 G460S, G460D, G460C,
449 9 E449K,
461 9
448 10 P448R, P448Q, P448L, P448S,
462 10 D462N
447 11 P447H,
463 11 S463T,
446 11 D446E, D446E, D446E, D446E, D446N,
464 11 S464P,
445 12
465 12
444 13 T444M, T444K,
466 13
443 13
467 13 K467R,
442 14 H442R,
468 14 S468G, S468N,
441 14 P441S,
469 14
440 15
470 15