SCN5A Variant L1921F

Summary of observed carriers, functional annotations, and structural context for SCN5A L1921F. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

2%

0/10 effective observations

Estimated BrS1 penetrance

11%

1/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

L1921F has not been reported in gnomAD. This residue resides in a Mild_Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 1 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 (%)
NA NA NA 0.243 11 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
Literature, cohort, and gnomAD 0 0 0 0
Variant features alone 15 14 0 1

Totals may differ from individual publications due to duplicate patients removed during curation.

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 L1921F.
Neighbour residue Distance (Å) Observed variants
1906 15 M1906V, M1906T,
1907 14
1908 14 I1908V,
1909 13 Q1909R,
1910 13 R1910K,
1911 12
1912 11
1913 11 R1913H, R1913C, R1913S,
1914 10 R1914G,
1915 9 H1915P, H1915Q, H1915Q, H1915N, H1915Y,
1916 8
1917 8
1918 7
1919 5 R1919H, R1919C,
1920 4 S1920C,
1921 0
1922 4 K1922N, K1922N, K1922R,
1923 5 H1923Y, H1923D,
1924 7 A1924T,
1925 8 S1925F, p.S1925CfsX20,
1926 8
1927 9 L1927P,
1928 10 F1928V,
1929 11 R1929C, R1929H,
1930 11 Q1930H, Q1930H,
1931 12
1932 13 A1932V,
1933 13 G1933A, G1933D, G1933V,
1934 14
1935 14 G1935S,
1936 15