SCN5A Variant V469I

Summary of observed carriers, functional annotations, and structural context for SCN5A V469I. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

4%

0/11 effective observations

Estimated BrS1 penetrance

5%

0/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

V469I is present in 1 alleles in gnomAD. This residue resides in a Non_Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 0 individuals for Brugada syndrome and 0 individuals for LQT3.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density BrS (%) Penetrance Density LQT3 (%)
-0.86 0.568 0.12 0.26 4 1

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. Penetrance density summarises neighbouring residue risk (Kroncke et al. 2019).

Reported carrier data

Observed carriers by publication or cohort.
Source Year Carriers Unaffected LQT3 BrS1 Other Other Disease
Literature, cohort, and gnomAD 1 1 0 0
Variant features alone 15 15 0 0

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 V469I.
Neighbour residue Distance (Å) Observed variants
454 15
455 14
456 14 V456M,
457 13
458 13 R458C, p.R458VfsX12, R458H,
459 12 S459G,
460 11
461 11 L461V,
462 10 E462A, E462K,
463 9 M463R, M463T,
464 8
465 8 p.P465LfsX5,
466 7 L466F, L466F,
467 5
468 4 P468L,
469 0 V469I,
470 4 N470K, N470K,
471 5
472 7
473 8 E473X,
474 8 R474G, R474K,
475 9 R475S, R475K, R475S,
476 10
477 11 c.1428_1431delCAAG,
478 11
479 12
480 13 K480N, K480N,
481 13 R481Q, R481W,
482 14 M482I, M482I, M482I
483 14
484 15