SCN5A Variant F1674V

Summary of observed carriers, functional annotations, and structural context for SCN5A F1674V. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

6%

0/13 effective observations

Estimated BrS1 penetrance

10%

1/13 effective observations

Total carriers

3

0 BrS1 · 0 LQT3 · 3 unaffected

F1674V is present in 3 alleles in gnomAD. This residue resides in a Non_Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 1 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 (%)
-6.71 0.997 2.09 0.938 10 0

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 – 3 3 0 0 –
Variant features alone – 15 14 0 1 – –

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 F1674V.
Neighbour residue Distance (Å) Observed variants
1746 12 A1746T, A1746V,
1281 14 c.3840+1G>A, V1281F,
1304 7 T1304M,
1745 14
1756 15 I1756V,
1299 15 c.3894delC,
1673 6
1675 4
1743 15 G1743R, G1743R, G1743E,
1754 10
1707 14
1694 10
1704 12 L1704H,
1226 11
1747 9 V1747M,
1695 15 Q1695X,
1669 10
1671 6
1668 12 M1668T,
1676 8 M1676T, M1676I, M1676I, M1676I,
1744 12 S1744I,
1219 14 S1219N,
1753 13 T1753A,
1672 7 S1672Y,
1310 15
1306 13 R1306S, R1306H,
1305 9
1680 12 A1680T, A1680P,
1703 14
1302 10 p.L1302Vfs18,
1701 14 M1701I, M1701I, M1701I,
1307 10
1758 13 I1758V, p.I1758del
1678 6 N1678S,
1223 13 c.3667delG,
1755 11
1697 14
1222 12 p.L1222LfsX7, L1222R,
1227 15
1300 11
1674 0 F1674V,
1748 10 p.G1748del, G1748D,
1301 8
1696 14
1700 11
1751 7
1311 14 L1311P,
1677 6
1682 14
1308 10 L1308F,
1750 10 L1750F,
1752 11
1670 7
1749 13 I1749N,
1225 13 E1225K, G1225K,
1720 13 c.5157delC,
1278 14 I1278N,
1679 8
1667 11 V1667I,
1303 12 R1303W, R1303Q,
1666 13