SCN5A Variant F402L

Summary of observed carriers, functional annotations, and structural context for SCN5A F402L. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

17%

1/12 effective observations

Estimated BrS1 penetrance

10%

1/12 effective observations

Total carriers

2

0 BrS1 · 0 LQT3 · 2 unaffected

F402L is present in 2 alleles in gnomAD. This residue resides in a Non_Hotspot region for Brugada syndrome and a Mild_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 1 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 (%)
-5.89 0.999 0.23 0.818 7 25

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 – 2 2 0 0 –
Variant features alone – 15 13 1 1 – –

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 F402L.
Neighbour residue Distance (Å) Observed variants
403 6
1659 14
404 8 L404V, L404Q,
1765 10
396 9 V396A, V396L,
1653 12
391 15
372 14
1771 9 I1771T,
401 4 S401P,
1764 7 c.5290delG, V1764F,
371 8 Q371E,
409 12 L409V, L409P,
1711 14 c.5131delG,
928 14 L928P,
1650 12 L1650F,
260 14
366 14
1707 14
1656 13
365 14
1706 14 Q1706H, Q1706H,
1762 14 p.I1762del, I1762M,
1668 14 M1668T,
1466 13 c.4396_4397insG,
369 9 M369K,
1767 5 Y1767C,
1660 10 I1660S, I1660V,
1654 12
1769 11
402 0 F402L, F402L, F402L,
1766 11 M1766V, M1766L, M1766L, M1766T,
1665 15
1768 8 I1768V,
1663 13
399 7
397 6 I397V, I397F, I397T,
405 7
1657 9
1759 11 S1759C,
261 14
1662 14
1709 9 T1709M, T1709R, p.T1709del,
392 14
1772 13 L1772V,
395 11
393 12
390 15
394 10
410 14 A410V,
1770 11 I1770V,
264 14
1658 12
1708 10 T1708I,
408 12
374 12 W374G,
1705 12
407 11
367 15 R367C, R367L, R367H,
1763 10 V1763L, V1763M, V1763L,
1760 11
370 10 T370M,
1661 10 G1661R, G1661R, G1661E,
1761 14 L1761H, c.5280delG, L1761F,
1655 14
1469 15 I1469V,
406 7 N406K, N406S, N406K,
368 11
1710 12 S1710L,
932 14
398 5
257 14
400 6 G400R, G400E, G400A, G400R,
1664 10