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

M1875T has not been reported 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 (%)
-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

Observed carriers by publication or cohort.
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.

Published electrophysiology measurements.
PubMed ID Year Cell Type Peak Current (% WT) V1/2 Activation (mV) V1/2 Inactivation (mV) Late/Persistent Current (% WT)
18929244 2008 HEK 151 -0.48 16.4
24096004 2014

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 M1875T.
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