SCN5A Variant L461V

Summary of observed carriers, functional annotations, and structural context for SCN5A L461V. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

0%

0/343 effective observations

Estimated BrS1 penetrance

0%

0/343 effective observations

Total carriers

333

0 BrS1 · 0 LQT3 · 333 unaffected

L461V is present in 329 alleles in gnomAD. This residue resides in a Non_Hotspot region for Brugada syndrome and a Mild_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 (%)
-0.55 0.08 -0.94 None 1 23

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
16712702 2006 1 0 0 1 Sudden adult death syndrome
22818067 2012 6 0 0 4 AF
20129283 2010 2 0 0 0
Literature, cohort, and gnomAD – 333 333 0 0 –
Variant features alone – 15 15 0 0 – –

Totals may differ from individual publications due to duplicate patients removed during curation.

Functional data

Peak and late/persistent current values are relative to wild-type (100% indicates no change). V1/2 activation and inactivation denote the membrane potentials (mV) at which half-maximal current is achieved.

Published electrophysiology measurements.
PubMed ID Year Cell Type Peak Current (% WT) V1/2 Activation (mV) V1/2 Inactivation (mV) Late/Persistent Current (% WT)
16712702 2006
22818067 2012
20129283 2010

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 L461V.
Neighbour residue Distance (Å) Observed variants
446 15 E446K,
447 14 c.1338+2T>A, c.1339-24G>A, A447S, A447G,
448 14
449 13 T449A, Y449C,
450 13
451 12
452 11 G452D,
453 11 V453M,
454 10
455 9
456 8 V456M,
457 8
458 7 p.R458VfsX12, R458C, R458H,
459 5 S459G,
460 4
461 0 L461V,
462 4 E462K, E462A,
463 5 M463T, M463R,
464 7
465 8 p.P465LfsX5,
466 8 L466F, L466F,
467 9
468 10 P468L,
469 11 V469I,
470 11 N470K, N470K,
471 12
472 13
473 13 E473X,
474 14 R474G, R474K,
475 14 R475K, R475S, R475S
476 15