SCN5A Variant A1924T
Summary of observed carriers, functional annotations, and structural context for SCN5A A1924T. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
0%
0/27 effective observations
Estimated BrS1 penetrance
9%
2/27 effective observations
Total carriers
17
1 BrS1 · 0 LQT3 · 16 unaffected
Variant features alone are equivalent to phenotyping 1 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -1.23 | 0.653 | 0.24 | 0.743 | 13 | 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 |
|---|---|---|---|---|---|---|---|
| 12106943 | 2002 | 1 | 0 | 1 | 0 | ||
| 20950709 | 2011 | 2 | 0 | 0 | 2 | sinus pauses, VT, conduction | |
| 21273195 | 2011 | 1 | 0 | 1 | 0 | ||
| 26111534 | 2015 | 2 | 0 | 0 | 2 | SND, AF, VT | |
| 19251209 | 2009 | 1 | 0 | 1 | 0 | ||
| 10690282 | 1999 | 1 | 0 | 1 | 0 | ||
| 20129283 | 2010 | 1 | 0 | 1 | 0 | ||
| Literature, cohort, and gnomAD | – | 17 | 16 | 0 | 1 | – | |
| Variant features alone | – | 15 | 14 | 0 | 1 | – | – |
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) |
|---|---|---|---|---|---|---|
| 12106943 | 2002 | |||||
| 20950709 | 2011 | |||||
| 21273195 | 2011 | |||||
| 26111534 | 2015 | |||||
| 19251209 | 2009 | |||||
| 19171938 | 2009 | |||||
| 11807557 | 2002 | HEK-tSA205 | ||||
| 16505387 | 2006 | tsA201 | 9.13 | |||
| 10690282 | 1999 | Xeno | -9 | -0.2 | 0 | |
| 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 |
|---|---|---|
| 1909 | 15 | Q1909R, |
| 1910 | 14 | R1910K, |
| 1911 | 14 | |
| 1912 | 13 | |
| 1913 | 13 | R1913S, R1913H, R1913C, |
| 1914 | 12 | R1914G, |
| 1915 | 11 | H1915P, H1915Y, H1915N, H1915Q, |
| 1916 | 11 | |
| 1917 | 10 | |
| 1918 | 9 | |
| 1919 | 8 | R1919C, R1919H, |
| 1920 | 8 | S1920C, |
| 1921 | 7 | |
| 1922 | 5 | K1922R, K1922N, |
| 1923 | 4 | H1923D, H1923Y, |
| 1924 | 0 | A1924T, |
| 1925 | 4 | p.S1925CfsX20, S1925F, |
| 1926 | 5 | |
| 1927 | 7 | L1927P, |
| 1928 | 8 | F1928V, |
| 1929 | 8 | R1929C, R1929H, |
| 1930 | 9 | Q1930H, |
| 1931 | 10 | |
| 1932 | 11 | A1932V, |
| 1933 | 11 | G1933D, G1933V, G1933A, |
| 1934 | 12 | |
| 1935 | 13 | G1935S, |
| 1936 | 13 | |
| 1937 | 14 | S1937A, |
| 1938 | 14 | E1938K, E1938X, |
| 1939 | 15 | p.E1939_E1943del, |