SCN5A Variant M1668T

Summary of observed carriers, functional annotations, and structural context for SCN5A M1668T. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

6%

0/11 effective observations

Estimated BrS1 penetrance

11%

1/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

M1668T is present in 1 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 (%)
-5.52 1 -1.5 0.95 6 5

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 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 M1668T.
Neighbour residue Distance (Å) Observed variants
1702 9
1659 15
387 14
1304 15 T1304M,
1757 14
391 14
1698 10 A1698T,
1756 13 I1756V,
1314 14 c.3940_3941delCT,
1220 14 G1220E,
1673 10
1675 11
1764 12 V1764F, c.5290delG,
1666 7
1711 13 c.5131delG,
1754 13
1707 9
1694 12
1704 5 L1704H,
1706 11 Q1706H, Q1706H,
1716 14 p.L1716SfsX71,
1669 7
1671 7
1762 14 p.I1762del, I1762M,
1668 0 M1668T,
1676 12 M1676I, M1676T, M1676I, M1676I,
1692 14
1219 14 S1219N,
1672 7 S1672Y,
1767 15 Y1767C,
1660 12 I1660V, I1660S,
1693 14
1699 12
378 13
1310 14
402 14 F402L, F402L, F402L,
1665 5
1703 9
1663 9
397 14 I397T, I397F, I397V,
1759 9 S1759C,
1662 10
1709 11 T1709M, T1709R, p.T1709del,
1701 5 M1701I, M1701I, M1701I,
1307 12
1758 11 p.I1758del, I1758V,
1223 12 c.3667delG,
1755 8
1697 11
1222 15 L1222R, p.L1222LfsX7,
393 15
1674 12 F1674V,
1713 14
394 11
390 11
1708 7 T1708I,
1696 13
374 15 W374G,
1705 6
1700 8
1763 11 V1763M, V1763L, V1763L,
1751 11
1311 13 L1311P,
1308 14 L1308F,
1760 14
1752 12
1670 7
1661 9 G1661R, G1661R, G1661E,
1710 14 S1710L,
1679 14
398 12
1667 5 V1667I,
1664 6