SCN5A Variant L404P

Summary of observed carriers, functional annotations, and structural context for SCN5A L404P. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

38%

1/10 effective observations

Estimated BrS1 penetrance

11%

1/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

L404P has not been reported in gnomAD. This residue resides in a Non_Hotspot region for Brugada syndrome and a 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 (%)
NA NA NA 0.982 5 49

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 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 L404P.
Neighbour residue Distance (Å) Observed variants
403 6
1643 12 I1643L,
404 0 L404V, L404Q,
249 15 K249X,
396 10 V396L, V396A,
247 15 V247L, V247L,
1653 13
254 9
1771 10 I1771T,
401 6 S401P,
1634 15 L1634P,
1764 14 c.5290delG, V1764F,
371 11 Q371E,
250 10
409 10 L409V, L409P,
928 10 L928P,
1650 9 L1650F,
260 8
366 10
365 12
258 11 V258A,
246 15
412 13 V412D,
924 12 V924I,
927 13 N927S, N927K, N927K,
369 6 M369K,
1767 11 Y1767C,
1654 13
1769 14
402 8 F402L, F402L, F402L,
1649 12 A1649V,
1768 11 I1768V,
1774 15 N1774D, c.5321_5324dupACTT,
262 13 S262G,
256 8
399 9
397 10 I397V, I397F, I397T,
405 5
1657 13
362 14
261 9
920 15
255 11
1772 12 L1772V,
395 13
251 13
410 10 A410V,
1770 14 I1770V,
264 12
929 13
1651 14
259 11
413 15 A413T, A413E,
408 6
253 8
407 5
367 15 R367C, R367H, R367L,
263 13 V263I,
1775 12 F1775V, p.F1775LfsX15
370 10 T370M,
1642 14 G1642E,
923 13
406 7 N406S, N406K, N406K,
368 12
252 13
411 11 V411M,
932 12
398 11
1647 11
257 6
400 5 G400R, G400R, G400E, G400A,
1646 10