SCN5A Variant V1451L

Summary of observed carriers, functional annotations, and structural context for SCN5A V1451L. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

1%

0/11 effective observations

Estimated BrS1 penetrance

32%

3/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

V1451L is present in 1 alleles in gnomAD. This residue resides in a Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 3 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 (%)
-2.86 0.856 -0.34 0.915 52 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 12 0 3 – –

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 V1451L.
Neighbour residue Distance (Å) Observed variants
891 12 I891N, I891T,
888 8
848 15 I848F,
1355 15
890 13 I890T,
896 10 C896S, C896S,
895 11 L895F,
1417 14
839 15 L839P,
1352 14
842 15
1445 12 Y1445H,
894 14 I894M,
1457 10
1453 7
1455 6
1447 6
1444 12 L1444I,
1351 13 M1351V, M1351R,
1449 7 Y1449S, Y1449C,
1452 4
1461 14 T1461S, T1461S
1429 13
1344 15 F1344L, F1344S, F1344L, F1344L,
1450 6
887 13
1451 0 V1451L, V1451D,
934 15
886 14 H886P, H886Q, H886Q,
1458 10 S1458Y,
851 14 c.2550_2551dupGT, F851L, p.F851CfsX19, c.2552_2553dupGT, F851L, F851L,
897 15 G897R, G897R, G897E,
1348 11 F1348L, F1348L, F1348L,
854 15 c.2559delT,
1422 13 M1422R,
1418 11
892 7 F892I,
1356 14 c.4066_4068delTT,
898 15
893 13 R893C, R893H,
1462 15
1412 12 L1412F,
840 15
889 9
843 11 T843A,
1456 9
1459 9 c.4376_4379delTCTT,
1460 14 F1460L, F1460L, F1460L,
1425 10
1454 5
1446 10
1424 14 I1424V,
1448 5 I1448L, I1448T,
884 13
1421 11
885 11
847 11
1345 15 W1345C, W1345C,
846 11 L846R,
1416 11 c.4245+1G>A, c.4245+1G>C, c.4245+2T>A, A1416E, A1416G,
879 14 W879R, W879R,
1347 15
1415 10
844 14 L844RfsX3,
1428 13 A1428S, A1428V,
850 12 V850M, c.2549_2550insTG,
931 14