SCN5A Variant R1919H
Summary of observed carriers, functional annotations, and structural context for SCN5A R1919H. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
3%
0/13 effective observations
Estimated BrS1 penetrance
19%
2/13 effective observations
Total carriers
3
1 BrS1 · 0 LQT3 · 2 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 (%) |
|---|---|---|---|---|---|
| -3.24 | 0.914 | 1.35 | 0.84 | 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 |
|---|---|---|---|---|---|---|---|
| 28341781 | 2017 | 1 | 0 | 1 | 0 | ||
| Literature, cohort, and gnomAD | – | 3 | 2 | 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) |
|---|---|---|---|---|---|---|
| 28341781 | 2017 |
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 |
|---|---|---|
| 1904 | 15 | S1904L, |
| 1905 | 14 | |
| 1906 | 14 | M1906T, M1906V, |
| 1907 | 13 | |
| 1908 | 13 | I1908V, |
| 1909 | 12 | Q1909R, |
| 1910 | 11 | R1910K, |
| 1911 | 11 | |
| 1912 | 10 | |
| 1913 | 9 | R1913S, R1913H, R1913C, |
| 1914 | 8 | R1914G, |
| 1915 | 8 | H1915P, H1915Y, H1915N, H1915Q, |
| 1916 | 7 | |
| 1917 | 5 | |
| 1918 | 4 | |
| 1919 | 0 | R1919C, R1919H, |
| 1920 | 4 | S1920C, |
| 1921 | 5 | |
| 1922 | 7 | K1922R, K1922N, |
| 1923 | 8 | H1923D, H1923Y, |
| 1924 | 8 | A1924T, |
| 1925 | 9 | p.S1925CfsX20, S1925F, |
| 1926 | 10 | |
| 1927 | 11 | L1927P, |
| 1928 | 11 | F1928V, |
| 1929 | 12 | R1929C, R1929H, |
| 1930 | 13 | Q1930H, |
| 1931 | 13 | |
| 1932 | 14 | A1932V, |
| 1933 | 14 | G1933D, G1933V, G1933A, |
| 1934 | 15 |