SCN5A Variant L382I

Summary of observed carriers, functional annotations, and structural context for SCN5A L382I. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

18%

0/10 effective observations

Estimated BrS1 penetrance

36%

3/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

L382I has not been reported in gnomAD. This residue resides in a Hotspot region for Brugada syndrome and a Mild_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 3 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 0.745 51 21

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 12 0 3 – –

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 L382I.
Neighbour residue Distance (Å) Observed variants
328 12
333 8 c.998+1G>A, c.998+5G>A,
271 12 L271V,
1702 7
326 11
276 10 L276Q, L276P,
387 7
348 14 P348A,
396 14 V396L, V396A,
385 6 A385T,
355 13 F355I, F355C,
1687 13
391 11
330 10 S330F,
278 12 H278D, H278R,
388 8 I388S,
1698 11 A1698T,
334 11 c.999-424_1338+81del,
1711 15 c.5131delG
332 7 A332T,
1704 14 L1704H,
327 10
1706 11 Q1706H, Q1706H,
376 12 R376C, R376H,
384 7 S384T,
1688 14
354 14
329 9
1692 7
386 4 G386R, G386R, G386E,
1693 12
378 5
1699 10
331 9
379 7
1703 11
272 10
341 15 C341Y,
397 15 I397V, I397F, I397T,
274 14 G274C,
335 15 C335S, C335R, C335S,
1701 12 M1701I, M1701I, M1701I,
325 9 L325R,
1690 13 c.5068_5070delGA, D1690N,
392 10
324 12
1697 15
389 7 Y389H, Y389X,
395 15
393 8
394 12
390 8
275 11 N275K, N275K,
383 7
382 0
374 11 W374G,
1696 14
1705 11
1689 10 D1689N,
1700 13
381 4 c.1140+1G>A, c.1141-3C>A,
375 11
1691 7
368 14
380 8
268 14 G268S,
377 9
353 14 T353I,