KCNQ1 Variant V416M

Summary of observed carriers, functional annotations, and structural context for KCNQ1 V416M. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

15%

2/14 effective observations

Total carriers

4

0 LQT1 · 4 unaffected

Functional studies

0

Publications with functional data

V416M is present in 3 alleles in gnomAD. This residue resides in a Mild_Hotspot region for LQT1.

Variant features alone are equivalent to phenotyping 2 individuals with LQT1 and 8 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT1 (%)
-0.32 0.004 1 0.496 18

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
32405922 2020 1 1 None None
Literature, cohort, and gnomAD – 4 4 0 –
Variant features alone – 15 8 2 –

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 V416M.
Neighbour residue Distance (Å) Observed variants
416 0 V416M,
415 4
417 4 V417M,
414 5
418 5 V418I,
413 7 K413R,
419 7
412 8 P412S
420 8 K420E, K420N, K420N,
411 8
421 8 K421N, K421N,
410 9
422 9 K422T, K422R,
409 10
423 10
408 11 P408A,
424 11 K424T,
407 11
425 11 L425V,
406 12
426 12
405 13
427 13
404 13
428 13 D428G,
403 14 H403P,
429 14 N429S,
402 14
430 14
401 15 R401W, R401Q,
431 15 V431L, V431L,