SCN5A Variant R475I

Summary of observed carriers, functional annotations, and structural context for SCN5A R475I. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

3%

0/10 effective observations

Estimated BrS1 penetrance

19%

1/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

R475I 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 0.553 22 0

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 R475I.
Neighbour residue Distance (Å) Observed variants
460 15
461 14 L461V,
462 14 E462K, E462A,
463 13 M463T, M463R,
464 13
465 12 p.P465LfsX5,
466 11 L466F, L466F,
467 11
468 10 P468L,
469 9 V469I,
470 8 N470K, N470K,
471 8
472 7
473 5 E473X,
474 4 R474G, R474K,
475 0 R475K, R475S, R475S,
476 4
477 5 c.1428_1431delCAAG,
478 7
479 8
480 8 K480N, K480N,
481 9 R481W, R481Q,
482 10 M482I, M482I, M482I,
483 11
484 11
485 12
486 13 T486A, T486S, T486S,
487 13
488 14
489 14
490 15 G490E, G490A