KCNQ1 Variant P448Q

Summary of observed carriers, functional annotations, and structural context for KCNQ1 P448Q. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

5%

1/28 effective observations

Total carriers

18

0 LQT1 · 18 unaffected

Functional studies

0

Publications with functional data

P448Q is present in 18 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 (%)
-0.77 0.001 -1 0.512 4

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 – 18 18 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 P448Q.
Neighbour residue Distance (Å) Observed variants
448 0 P448R, P448Q, P448L, P448S,
447 4 P447H,
449 4 E449K,
446 5 D446E, D446E, D446E, D446E, D446N,
450 5 E450K,
445 7
451 7 R451Q, R451W,
444 8 T444M, T444K,
452 8 R452Q, R452W, R452L,
443 8
453 8
442 9 H442R,
454 9
441 10 P441S,
455 10 H455Y, H455Q, H455Q, H455R,
440 11
456 11 F456L, F456L, F456L,
439 11
457 11
438 12
458 12
437 13 M437V,
459 13 D459N, D459V,
436 13
460 13 G460S, G460D, G460C,
435 14
461 14
434 14 G434R, G434R,
462 14 D462N
433 15 P433A,
463 15 S463T,