SCN5A Variant W374L

Summary of observed carriers, functional annotations, and structural context for SCN5A W374L. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

8%

0/10 effective observations

Estimated BrS1 penetrance

51%

5/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

W374L has not been reported in gnomAD. This residue resides in a Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 5 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 0.921 77 6

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 0 5 – –

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 W374L.
Neighbour residue Distance (Å) Observed variants
364 10
1702 11
901 15 E901K, S901L,
276 14 L276P, L276Q,
363 14
1417 14
396 10 V396L, V396A,
355 14 F355C, F355I,
1715 14
1687 14
391 14
372 8
401 11 S401P,
1764 14 c.5290delG, V1764F,
371 6 Q371E,
1711 6 c.5131delG,
361 15
366 12
1707 10
365 11
1704 12 L1704H,
1706 6 Q1706H, Q1706H,
1716 13 p.L1716SfsX71,
1714 15 D1714G,
376 9 R376C, R376H,
897 12 G897R, G897E, G897R,
1668 15 M1668T,
1692 12
386 14 G386E, G386R, G386R,
369 11 M369K,
378 6
1418 14
402 12 F402L, F402L, F402L,
349 15 D349N,
373 7
1712 9 G1712C, G1712S,
379 9
1703 11
898 12
399 14
272 15
397 7 I397T, I397V, I397F,
405 15
1759 14 S1759C,
1709 7 T1709M, p.T1709del, T1709R,
1701 14 M1701I, M1701I, M1701I,
900 12
392 11
1755 15
389 14 Y389X, Y389H,
395 13
393 7
1713 12
390 12
394 11
383 15
264 14
1708 10 T1708I,
382 11
374 0 W374G,
1705 9
367 8 R367C, R367L, R367H,
1760 13
370 9 T370M,
381 10 c.1140+1G>A, c.1141-3C>A,
375 6
368 6
899 12
1710 9 S1710L,
380 11
377 6
398 13
400 13 G400R, G400E, G400A, G400R,
1419 11 K1419E,
353 13 T353I,
1664 15