SCN5A Variant R451T

Summary of observed carriers, functional annotations, and structural context for SCN5A R451T. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

6%

0/10 effective observations

Estimated BrS1 penetrance

17%

1/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

R451T 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 1 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 0.63 18 5

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 14 0 1 – –

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 R451T.
Neighbour residue Distance (Å) Observed variants
436 15
437 14 A437V,
438 14 M438L, M438L, M438T,
439 13 E439K, E439V,
440 13
441 12 L441F,
442 11
443 11
444 10 E444fsX14,
445 9 H445D, H445Y, H445Q, H445Q,
446 8 E446K,
447 8 c.1338+2T>A, c.1339-24G>A, A447S, A447G,
448 7
449 5 T449A, Y449C,
450 4
451 0
452 4 G452D,
453 5 V453M,
454 7
455 8
456 8 V456M,
457 9
458 10 p.R458VfsX12, R458C, R458H,
459 11 S459G,
460 11
461 12 L461V,
462 13 E462K, E462A,
463 13 M463T, M463R,
464 14
465 14 p.P465LfsX5,
466 15 L466F, L466F