SCN5A Variant V1468A

Summary of observed carriers, functional annotations, and structural context for SCN5A V1468A. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

4%

0/11 effective observations

Estimated BrS1 penetrance

28%

3/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

V1468A 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 (%)
-3.8 0.279 -1.45 0.95 43 7

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 V1468A.
Neighbour residue Distance (Å) Observed variants
1328 13 V1328M,
939 9 L939F,
937 14
1773 13
1765 9
943 9 S943N,
1340 13 V1340I,
1757 13
1472 6 p.N1472del, N1472S,
1339 14 L1339F, p.L1339del,
1461 11 T1461S, T1461S,
1764 13 c.5290delG, V1764F,
409 15 L409V, L409P,
1333 6
934 14
1477 15 K1477N, K1477N,
1471 6
935 11 L935P,
1762 10 p.I1762del, I1762M,
1470 6
1464 7 c.4389_4396delCCTCTTTA, L1464P,
1466 6 c.4396_4397insG,
944 9
1329 10 G1329S,
1769 10
1766 10 M1766L, M1766V, M1766L, M1766T,
1768 11 I1768V,
940 13 S940N,
1473 9 F1473S, F1473C,
1334 7 I1334V,
1341 13
1468 0 V1468F, V1468A,
831 14
1462 12
938 10
1474 11
1327 12
942 9
1758 14 I1758V, p.I1758del,
1330 7 A1330T, A1330P, A1330D,
1772 13 L1772V
827 14
1460 12 F1460L, F1460L, F1460L,
1323 14 V1323G,
1338 12 L1338V,
1770 14 I1770V,
941 12 S941N, S941F,
1337 8
1326 10 A1326S,
936 13
1763 13 V1763M, V1763L, V1763L,
1332 10 P1332Q, P1332L,
1465 7 p.F1465_L1480dup,
1760 14
1467 4
1476 13 Q1476X, Q1476R,
1331 10 I1331V,
1761 11 c.5280delG, L1761F, L1761H,
1475 12 p.Q1475NfsX6, Q1475L,
1469 5 I1469V,
1336 10
824 14
1325 15 N1325S,
1335 12 M1335R,
828 13 L828V,
1463 10 N1463Y,