SCN5A Variant F1348L

Summary of observed carriers, functional annotations, and structural context for SCN5A F1348L. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

3%

0/11 effective observations

Estimated BrS1 penetrance

25%

2/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

F1348L is present in 1 alleles in gnomAD. This residue resides in a Mild_Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 2 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 (%)
-5.84 0.999 -2.73 0.918 34 1

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

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 F1348L.
Neighbour residue Distance (Å) Observed variants
1355 11
1357 14 A1357V,
811 14 R811H, c.2435_2436+3delTGGTAinsCGCCT, R811G
1417 15
808 15 R808P, R808C, R808H,
1352 8
1406 13 G1406R, G1406R, G1406E,
1340 12 V1340I,
1457 9
1453 5
1455 10
1447 14
1339 15 L1339F, p.L1339del,
1351 5 M1351R, M1351V,
1449 6 Y1449S, Y1449C,
1452 7
1461 11 T1461S, T1461S,
812 9 L812Q,
1350 8 I1350L, I1350T,
1344 7 F1344L, F1344L, F1344S, F1344L,
731 14 T731I,
806 15 V806M,
1450 9
1411 11
1451 11 V1451L, V1451D,
1353 11 V1353M,
1407 14
737 15
1458 12 S1458Y,
1410 14
1348 0 F1348L, F1348L, F1348L,
1404 14
1349 6
1346 8 L1346I, L1346P,
1341 11
1356 11 c.4066_4068delTT,
1462 14
1412 8 L1412F,
810 13
1408 10 G1408R, G1408R,
735 13 A735V, A735E, A735T,
1456 8
1459 14 c.4376_4379delTCTT,
734 13 M734V, c.2201dupT,
1460 13 F1460L, F1460L, F1460L,
816 11 F816L, F816L, F816L, F816Y,
1425 14
813 12 c.2436+12G>A, c.2437-5C>A,
1454 10
1354 11
1446 13
1424 14 I1424V,
1448 11 I1448T, I1448L,
1405 11 V1405M, V1405L, V1405L,
809 11
1409 10 Y1409C, Y1409X,
815 11
1343 10
1345 7 W1345C, W1345C,
1342 11
1416 11 A1416E, c.4245+2T>A, c.4245+1G>C, c.4245+1G>A, A1416G,
1347 5
1415 11
1428 15 A1428V, A1428S,
1414 14 Q1414H, Q1414H,
1402 11
1413 12