SCN5A Variant Y378D

Summary of observed carriers, functional annotations, and structural context for SCN5A Y378D. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

12%

0/10 effective observations

Estimated BrS1 penetrance

32%

3/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

Y378D 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 0.967 43 12

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 Y378D.
Neighbour residue Distance (Å) Observed variants
333 13 c.998+1G>A, c.998+5G>A,
364 13
271 14 L271V,
1702 6
326 15
276 12 L276P, L276Q,
387 10
348 14 P348A,
396 11 V396L, V396A,
385 10 A385T,
355 13 F355C, F355I,
1715 14
1687 12
391 11
372 13
388 11 I388S,
1698 12 A1698T,
401 15 S401P,
371 12 Q371E,
1711 10 c.5131delG,
332 12 A332T,
1707 11
1694 15
365 13
1704 11 L1704H,
327 15
1706 6 Q1706H, Q1706H,
1716 13 p.L1716SfsX71,
376 9 R376C, R376H,
1688 13
384 11 S384T,
354 15
329 14
1668 13 M1668T,
1692 8
386 9 G386E, G386R, G386R,
1693 13
378 0
1699 11
331 13
373 11
1712 11 G1712C, G1712S,
379 5
1703 8
272 12
397 10 I397T, I397V, I397F,
1709 11 T1709M, p.T1709del, T1709R,
1701 11 M1701I, M1701I, M1701I,
325 12 L325R,
392 10
324 14
389 9 Y389X, Y389H,
395 13
393 6
1713 14
390 8
394 10
275 14 N275K, N275K,
383 10
1708 12 T1708I,
382 5
374 6 W374G,
1705 7
1689 12 D1689N,
1700 12
367 12 R367C, R367L, R367H,
370 15 T370M,
381 6 c.1140+1G>A, c.1141-3C>A,
375 7
1691 10
368 10
1710 13 S1710L,
380 8
268 14 G268S,
377 7
398 14
353 14 T353I,