KCNQ1 Variant M476V

Summary of observed carriers, functional annotations, and structural context for KCNQ1 M476V. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

39%

4/11 effective observations

Total carriers

1

0 LQT1 · 1 unaffected

Functional studies

0

Publications with functional data

M476V is present in 1 alleles in gnomAD. This residue resides in a Hotspot region for LQT1.

Variant features alone are equivalent to phenotyping 4 individuals with LQT1 and 6 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT1 (%)
-0.16 0.001 -3 0.362 44

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 – 1 1 0 –
Variant features alone – 15 6 4 –

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 M476V.
Neighbour residue Distance (Å) Observed variants
476 0 M476L, M476L, M476V,
475 4
477 4 P477L, P477T,
474 5
478 5 H478Y,
473 7 E473Q,
479 7 F479L, F479L, F479L,
472 8 L472P,
480 8 M480T,
471 8
481 8
470 9
482 9 T482N, T482A, T482S, T482S,
469 10
483 10
468 11 S468G, S468N,
484 11
467 11 K467R,
485 11 F485S,
466 12
486 12 A486T,
465 13
487 13 E487K,
464 13 S464P,
488 13 D488E, D488E,
463 14 S463T,
489 14
462 14 D462N
490 14
461 15
491 15