SCN5A Variant F1486L

Summary of observed carriers, functional annotations, and structural context for SCN5A F1486L. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

71%

4/11 effective observations

Estimated BrS1 penetrance

7%

0/11 effective observations

Total carriers

1

0 BrS1 · 1 LQT3 · 0 unaffected

F1486L 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 0 individuals for Brugada syndrome and 3 individuals for LQT3.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density BrS (%) Penetrance Density LQT3 (%)
-5.58 0.092 2.18 0.824 1 87

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
17210841 2007 1 0 0 1 SIDS
22360817 2012 1 1 0 0
30059973 2018 1 1 0 0
Literature, cohort, and gnomAD – 1 0 1 0 –
Variant features alone – 15 12 3 0 – –

Totals may differ from individual publications due to duplicate patients removed during curation.

Functional data

Peak and late/persistent current values are relative to wild-type (100% indicates no change). V1/2 activation and inactivation denote the membrane potentials (mV) at which half-maximal current is achieved.

Published electrophysiology measurements.
PubMed ID Year Cell Type Peak Current (% WT) V1/2 Activation (mV) V1/2 Inactivation (mV) Late/Persistent Current (% WT)
17210841 2007 tsA201 100 3.7 14.3 518
30059973 2018
22360817 2012
17646591 2007
20038812 2010 DRG 8 320

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 F1486L.
Neighbour residue Distance (Å) Observed variants
1875 12 M1875K, M1875T, p.M1875dup,
1872 14 K1872N, K1872N,
1496 13
1474 15
1491 6 Q1491H, Q1491H,
1481 12 G1481V, G1481R, G1481E, G1481R,
1874 13
1493 11 p.K1493del, K1493X, K1493R,
1484 8
1486 0 F1486L, p.F1486del, F1486L, F1486L,
1478 11 K1478E,
1488 6 T1488R,
1475 14 p.Q1475NfsX6, Q1475L,
1490 9
1498 15 M1498V, M1498T, M1498R,
1483 6 Q1483H, Q1483H,
1485 4
1494 11
1487 7 M1487L, M1487L, M1487K,
1495 10 Y1495S,
1869 14
1876 14
1479 15
1482 10
1489 9 E1489D, E1489D,
1492 8
1868 15