SCN5A Variant K443I

Summary of observed carriers, functional annotations, and structural context for SCN5A K443I. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

5%

0/10 effective observations

Estimated BrS1 penetrance

25%

2/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

K443I 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 0.635 32 4

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 K443I.
Neighbour residue Distance (Å) Observed variants
428 15 E428K,
429 14 E429K, p.E429del,
430 14 K430E,
431 13
432 13
433 12 R433H, R433S, R433C,
434 11
435 11
436 10
437 9 A437V,
438 8 M438T, M438L, M438L,
439 8 E439V, E439K,
440 7
441 5 L441F,
442 4
443 0
444 4 E444fsX14,
445 5 H445Q, H445Y, H445D, H445Q,
446 7 E446K,
447 8 c.1339-24G>A, A447G, A447S, c.1338+2T>A,
448 8
449 9 Y449C, T449A,
450 10
451 11
452 11 G452D,
453 12 V453M,
454 13
455 13
456 14 V456M,
457 14
458 15 R458H, R458C, p.R458VfsX12,