A1924T Summary

SCN5A A1924T was found in 10 papers (see below) with a total of 17 carriers: 1 had BrS1, 0 had LQT3, and 2 had other disease. A1924T is present in 16 out of 280642 alleles in gnomAD (minor allele frequency of 0.005701%). A1924T has been functionally characterized in 3 papers. Other variants at the same resdue are A1924D .A1924G .A1924P .A1924S .A1924T .A1924V . This residue is located in a Mild_Hotspot region for BrS1 and in a Non_Hotspot region for Long QT syndrome.

A1924T Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
1210694320020100
2095070920110002sinus pauses, VT, conduction
2127319520110100
2611153420150002SND, AF, VT
1925120920090100
1917193820090000
1180755720020000
1650538720060000
1069028219990100
2012928320100100
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

A1924T Reported Functional Data

Peak current and late current are relative % to wildtype. V0.5 act/inact are the voltages at which half of the maximal current is reached during an activation and inactivation protocol, each is in units of mV and relative to wildtype.

PMID Year Cell type Peak current V0.5 act V0.5 inact Rec from inact Late current
11807557 2002 HEK-tSA205 NA NA
16505387 2006 tsA201 NA 9.13 NA
10690282 1999 Xeno NA -9 -0.2 NA NA

A1924T Predictions

PROVEAN scores less than -2 are considered deleterious. REVEL scores higher than 0.5 or 0.75 is considered likely pathogenic (higher sensitivity with the former cutoff, higher specificity with the latter cutoff). A PolyPhen-2 score of 0.85 or greater is considered likely pathogenic. PAM scores reflect the chemistry difference between WT and variant amino acid (more negative being greater difference between the two). BLAST-PSSM reflects the evolutionary conservation of residue substitutions, more negative numbers indicate fewer observations of the specific substitution than is expected.

SIFT Sift Score PROVEAN Score Polyphen2 Polyphen2 Score eaRate blastPssm pamScore REVEL
Tolerated 0.056 -1.23 possiblydamaging 0.653 2.114 0.24 -1 0.743

A1924T has 30 neighbors within 15 ångströms that have been found in individuals.

A residue within a folded protein on average has nearest neighbors that fall roughly into two shells: a "nearest" neighbor around 5-6 angstroms and a second shell around 11 angstroms.

ResidueNumber Distance(Å) Variants
1909 14.7
1910 14.2
1911 13.7
1912 13.2
1913 12.6 R1913C R1913H R1913S
1914 12 R1914G
1915 11.4 H1915Y
1916 10.7
1917 10.1
1918 9.3
1919 8.5 R1919C R1919H
1920 7.6
1921 6.6
1922 5.4 K1922N K1922N
1923 3.8
1925 3.8
1926 5.4
1927 6.6
1928 7.6
1929 8.5 R1929C R1929H
1930 9.3
1931 10.1
1932 10.7 A1932V
1933 11.4 G1933A G1933D
1934 12
1935 12.6 G1935S
1936 13.2
1937 13.7
1938 14.2 E1938K
1939 14.7