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

A1924T is present in 16 alleles 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 (%)
-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

Observed carriers by publication or cohort.
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.

Published electrophysiology measurements.
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.

Previously observed variants near A1924T.
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 H1915N, H1915Y, H1915Q, H1915P, H1915Q,
1916 11
1917 10
1918 9
1919 8 R1919H, R1919C,
1920 8 S1920C,
1921 7
1922 5 K1922R, K1922N, K1922N,
1923 4 H1923Y, H1923D,
1924 0 A1924T,
1925 4 S1925F, p.S1925CfsX20,
1926 5
1927 7 L1927P,
1928 8 F1928V,
1929 8 R1929C, R1929H,
1930 9 Q1930H, 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,