SCN5A Variant R383M

Summary of observed carriers, functional annotations, and structural context for SCN5A R383M. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

12%

0/10 effective observations

Estimated BrS1 penetrance

29%

2/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

R383M has not been reported in gnomAD. This residue resides in a Mild_Hotspot region for Brugada syndrome and a Mild_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 0.919 38 13

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 R383M.
Neighbour residue Distance (Å) Observed variants
328 11
333 5 c.998+5G>A, c.998+1G>A,
277 14
1702 12
326 5
276 10 L276P, L276Q,
387 11
348 11 P348A,
279 11
385 8 A385T,
1687 11
330 12 S330F,
278 10 H278R, H278D,
388 13 I388S,
1698 14 A1698T,
334 7 c.999-424_1338+81del,
332 6 A332T,
327 7
1706 14 Q1706H, Q1706H,
339 14
376 11 R376H, R376C,
384 6 S384T,
1688 12
1684 12 W1684R, W1684R,
329 10
1692 8
386 8 G386R, G386E, G386R,
1693 12
378 10
1699 12
331 10
349 14 D349N,
379 7
1703 13
272 13
341 11 C341Y,
274 14 G274C,
335 10 C335S, C335S, C335R,
325 5 L325R,
1690 10 c.5068_5070delGA, D1690N,
324 6
389 12 Y389X, Y389H,
393 14
390 14
275 12 N275K, N275K,
383 0
280 9 C280Y,
323 10
347 14
382 7
374 15 W374G,
1689 7 D1689N,
342 14
336 11 P336L,
381 8 c.1141-3C>A, c.1140+1G>A,
1686 14
322 14
375 12
1691 6
380 7
377 11
281 14 V281M,
353 14 T353I,