SCN5A Variant K1872N
Summary of observed carriers, functional annotations, and structural context for SCN5A K1872N. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
7%
0/11 effective observations
Estimated BrS1 penetrance
46%
5/11 effective observations
Total carriers
1
1 BrS1 · 0 LQT3 · 0 unaffected
Variant features alone are equivalent to phenotyping 4 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -3.07 | 0.999 | 1.65 | 0.865 | 61 | 6 |
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 |
|---|---|---|---|---|---|---|---|
| 20129283 | 2010 | 1 | 0 | 1 | 0 | ||
| Literature, cohort, and gnomAD | – | 1 | 0 | 0 | 1 | – | |
| Variant features alone | – | 15 | 11 | 0 | 4 | – | – |
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.
| PubMed ID | Year | Cell Type | Peak Current (% WT) | V1/2 Activation (mV) | V1/2 Inactivation (mV) | Late/Persistent Current (% WT) |
|---|---|---|---|---|---|---|
| 20129283 | 2010 |
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 |
|---|---|---|
| 1875 | 9 | p.M1875dup, M1875K, M1875T, |
| 1872 | 0 | K1872N, K1872N, |
| 1878 | 9 | |
| 1870 | 6 | A1870T, |
| 1491 | 12 | Q1491H, Q1491H, |
| 1871 | 7 | |
| 1863 | 14 | |
| 1874 | 5 | |
| 1862 | 14 | |
| 1867 | 10 | |
| 1873 | 5 | I1873V, |
| 1879 | 13 | |
| 1881 | 15 | |
| 1877 | 9 | E1877K, |
| 1486 | 14 | F1486L, F1486L, p.F1486del, F1486L, |
| 1488 | 15 | T1488R, |
| 1490 | 14 | |
| 1880 | 14 | M1880V, |
| 1866 | 13 | |
| 1494 | 13 | |
| 1859 | 14 | |
| 1869 | 5 | |
| 1876 | 12 | |
| 1868 | 10 |