SCN5A Variant F1460L

Summary of observed carriers, functional annotations, and structural context for SCN5A F1460L. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

55%

3/11 effective observations

Estimated BrS1 penetrance

22%

2/11 effective observations

Total carriers

1

0 BrS1 · 1 LQT3 · 0 unaffected

F1460L has not been reported in gnomAD. This residue resides in a Mild_Hotspot region for Brugada syndrome and a Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 2 individuals for Brugada syndrome and 2 individuals for LQT3.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density BrS (%) Penetrance Density LQT3 (%)
-5.73 0.967 -0.98 0.968 29 59

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
30059973 2018 1 1 0 0
Literature, cohort, and gnomAD – 1 0 1 0 –
Variant features alone – 15 11 2 2 – –

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)
30059973 2018

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 F1460L.
Neighbour residue Distance (Å) Observed variants
939 12 L939F,
896 14 C896S,
937 10
1417 15
1765 15
839 9 L839P,
842 12
943 15 S943N,
1340 9 V1340I,
1457 6
1453 11
1455 8
1339 14 L1339F, p.L1339del,
1452 12
1461 4 T1461S,
1344 9 F1344L, F1344S,
836 12 V836M,
1451 14 V1451L, V1451D,
825 13
934 7
1458 8 S1458Y,
933 13
935 10 L935P,
1348 13 F1348L,
1464 6 c.4389_4396delCCTCTTTA, L1464P,
1466 11 c.4396_4397insG,
944 15
830 15
833 12 G833R,
1418 15
940 13 S940N
1341 9
1334 14 I1334V,
1468 12 V1468F, V1468A,
831 10
1462 8
938 7
840 12
942 9
843 11 T843A,
1456 6
930 14 c.2788-6C>T, c.2787+17_2787+18insACACACACACACACACACACACA,
1459 7 c.4376_4379delTCTT,
834 14 N834D,
827 13
1460 0 F1460L,
816 15 F816Y, F816L,
837 14
1454 10
1338 13 L1338V,
1343 13
1345 11 W1345C,
941 10 S941F, S941N,
1337 10
846 14 L846R,
1342 14
936 12
1416 12 A1416E, A1416G, c.4245+2T>A, c.4245+1G>C, c.4245+1G>A,
838 12
1465 10 p.F1465_L1480dup,
1467 11
1761 14 L1761F, L1761H, c.5280delG,
1347 14
1469 15 I1469V,
1336 14
1415 15
824 14
829 11
932 14
832 8
835 10 S835L, S835A,
828 9 L828V,
931 11
1463 7 N1463Y,