KCNQ1 Variant V417M

Summary of observed carriers, functional annotations, and structural context for KCNQ1 V417M. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

63%

10/17 effective observations

Total carriers

7

7 LQT1 · 0 unaffected

Functional studies

1

Publications with functional data

V417M has not been reported in gnomAD. This residue resides in a Hotspot region for LQT1.

Variant features alone are equivalent to phenotyping 3 individuals with LQT1 and 7 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT1 (%)
-0.25 0.0 2 0.551 57

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
14756674 2004 7 None 7 None
Literature, cohort, and gnomAD – 7 0 7 –
Variant features alone – 15 7 3 –

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 V417M.
Neighbour residue Distance (Å) Observed variants
417 0 V417M,
416 4 V416M,
418 4 V418I,
415 5
419 5
414 7
420 7 K420E, K420N, K420N,
413 8 K413R,
421 8 K421N, K421N,
412 8 P412S,
422 8 K422T, K422R,
411 9
423 9
410 10
424 10 K424T,
409 11
425 11 L425V,
408 11 P408A,
426 11
407 12
427 12
406 13
428 13 D428G,
405 13
429 13 N429S,
404 14
430 14
403 14 H403P,
431 14 V431L, V431L,
402 15
432 15 T432I, T432A