SCN5A Variant I450M

Summary of observed carriers, functional annotations, and structural context for SCN5A I450M. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

6%

0/10 effective observations

Estimated BrS1 penetrance

22%

2/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

I450M has not been reported in gnomAD. This residue resides in a Mild_Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 2 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 (%)
NA NA NA 0.389 29 6

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 – 0 0 0 0 –
Variant features alone – 15 13 0 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 I450M.
Neighbour residue Distance (Å) Observed variants
435 15
436 14
437 14 A437V,
438 13 M438T, M438L, M438L,
439 13 E439V, E439K,
440 12
441 11 L441F,
442 11
443 10
444 9 E444fsX14,
445 8 H445Q, H445Q, H445Y, H445D,
446 8 E446K,
447 7 c.1339-24G>A, A447S, A447G, c.1338+2T>A,
448 5
449 4 T449A, Y449C,
450 0
451 4
452 5 G452D,
453 7 V453M,
454 8
455 8
456 9 V456M,
457 10
458 11 R458C, R458H, p.R458VfsX12,
459 11 S459G,
460 12
461 13 L461V,
462 13 E462A, E462K,
463 14 M463R, M463T
464 14
465 15 p.P465LfsX5,