SCN5A Variant M1875T
Summary of observed carriers, functional annotations, and structural context for SCN5A M1875T. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
2%
0/11 effective observations
Estimated BrS1 penetrance
5%
0/11 effective observations
Total carriers
1
0 BrS1 · 0 LQT3 · 1 unaffected
Variant features alone are equivalent to phenotyping 0 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
---|---|---|---|---|---|
-5.55 | 0.322 | -0.73 | 0.968 | 3 | 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
Source | Year | Carriers | Unaffected | LQT3 | BrS1 | Other | Other Disease |
---|---|---|---|---|---|---|---|
18929244 | 2008 | 5 | 0 | 0 | 4 | AF | |
24096004 | 2014 | 1 | 0 | 0 | 1 | AF | |
Literature, cohort, and gnomAD | – | 1 | 1 | 0 | 0 | – | |
Variant features alone | – | 15 | 15 | 0 | 0 | – | – |
Totals may differ from individual publications due to duplicate patients removed during curation.
Functional data
Peak and late/persistent current values are relative to wild-type (100% indicates no change). V1/2 activation and inactivation denote the membrane potentials (mV) at which half-maximal current is achieved.
Nearby variants
Neighbouring residues within 15 Ångström provide structural context. Variants listed in the right-most column have been observed clinically or in gnomAD.
Neighbour residue | Distance (Å) | Observed variants |
---|---|---|
1855 | 15 | |
1875 | 0 | M1875T, p.M1875dup, M1875K, |
1872 | 9 | K1872N, K1872N, |
1884 | 14 | P1884L, |
1878 | 4 | |
1491 | 10 | Q1491H, Q1491H |
1871 | 14 | |
1870 | 14 | A1870T, |
1874 | 6 | |
1873 | 7 | I1873V, |
1879 | 5 | |
1881 | 10 | |
1877 | 7 | E1877K, |
1486 | 12 | F1486L, F1486L, F1486L, p.F1486del, |
1882 | 10 | |
1885 | 15 | |
1883 | 12 | |
1483 | 14 | Q1483H, Q1483H, |
1498 | 13 | M1498T, M1498V, M1498R, |
1880 | 10 | M1880V, |
1485 | 14 | |
1494 | 11 | |
1495 | 13 | Y1495S, |
1859 | 14 | |
1869 | 12 | |
1876 | 5 |