SCN5A Variant T381N

Summary of observed carriers, functional annotations, and structural context for SCN5A T381N. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

24%

1/10 effective observations

Estimated BrS1 penetrance

43%

4/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

T381N 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 4 individuals for Brugada syndrome and 1 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 0.93 62 30

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 10 1 4 – –

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 T381N.
Neighbour residue Distance (Å) Observed variants
328 12
333 11 c.998+5G>A, c.998+1G>A,
364 12
277 12
271 10 L271V,
1702 11
326 11
276 6 L276P, L276Q,
387 10
348 11 P348A,
270 15 Q270K,
279 13
396 13 V396L, V396A,
385 6 A385T,
355 9 F355I, F355C,
1687 15
391 12
330 13 S330F,
278 10 H278D, H278R,
388 10 I388S,
1698 15 A1698T,
356 14 D356N,
334 13 c.999-424_1338+81del,
361 13
332 9 A332T,
343 14
365 13
327 10
1706 12 Q1706H, Q1706H,
376 10 R376C, R376H
384 6 S384T,
354 10
329 11
1692 11
386 6 G386E, G386R, G386R,
378 6
1699 14
331 13
349 13 D349N,
373 14
267 13
379 7
1703 14
272 7
341 14 C341Y,
397 14 I397T, I397V, I397F,
274 10 G274C,
273 13
325 8 L325R,
392 9
324 12
389 7 Y389X, Y389H,
269 14
395 14
393 8
394 13
390 10
275 8 N275K, N275K,
383 8
280 15 C280Y,
264 15
323 14
347 12
382 4
351 15 G351S, G351C, G351V, G351D,
265 14 A265V,
374 10 W374G,
1705 13
1689 13 D1689N,
367 12 R367C, R367L, R367H,
381 0 c.1140+1G>A, c.1141-3C>A,
375 11
1691 11
368 11
380 5
268 10 G268S,
377 6
353 10 T353I,