SCN5A Variant M1676I

Summary of observed carriers, functional annotations, and structural context for SCN5A M1676I. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

1%

0/15 effective observations

Estimated BrS1 penetrance

6%

0/15 effective observations

Total carriers

5

0 BrS1 · 0 LQT3 · 5 unaffected

M1676I is present in 5 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 0 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 (%)
-3.83 0.995 -1.26 0.951 4 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 – 5 5 0 0 –
Variant features alone – 15 15 0 0 – –

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 M1676I.
Neighbour residue Distance (Å) Observed variants
1702 12
1741 15 D1741Y, D1741E, D1741N, D1741E,
1304 10 T1304M,
1698 9 A1698T,
1220 13 G1220E,
1673 5
1675 4
1743 14 G1743R, G1743R, G1743E,
1707 14
1681 10 c.5040_5042delTTAinsC, Y1681F,
1694 6
1704 11 L1704H,
1226 5
1747 13 V1747M,
1695 7 Q1695X,
1716 14 p.L1716SfsX71,
1688 14
1669 10
1671 10
1221 13 A1221V,
1668 12 M1668T,
1676 0 M1676I, M1676I, M1676T, M1676I,
1692 13
1744 13 S1744I,
1219 13 S1219N,
1672 5 S1672Y,
1693 9
1699 9
1239 14 L1239P,
1665 15
1305 14
1680 7 A1680P, A1680T,
1703 11
1235 15
1302 14 p.L1302Vfs18,
1701 10 M1701I, M1701I, M1701I,
1307 13
1228 11 Y1228C, Y1228F, Y1228H,
1690 15 D1690N, c.5068_5070delGA,
1678 7 N1678S,
1223 8 c.3667delG,
1755 14
1697 8
1222 10 p.L1222LfsX7, L1222R,
1227 8
1300 13
1674 8 F1674V,
1229 12
1748 14 G1748D, p.G1748del,
1301 10
1696 7
1705 15
1700 7
1751 11
1677 5
1682 11
1752 14
1224 11
1670 10
1740 14 G1740R, G1740R,
1225 8 G1225K, E1225K,
1691 14
1720 13 c.5157delC,
1679 7
1667 14 V1667I,
1303 13 R1303Q, R1303W,
1666 15