A2T Summary
SCN5A A2T was found in 2 papers (see below) with a total of 5 carriers: 1 had BrS1, 0 had LQT3, and 0 had other disease. A2T is present in 3 out of 245592 alleles in gnomAD (minor allele frequency of 0.001222%). A2T has been functionally characterized in 0 papers. Other variants at the same resdue are A2E .A2G .A2P .A2S .A2T .A2V .
This residue is located in a Mild_Hotspot region for BrS1 and in a Non_Hotspot region for Long QT syndrome.
A2T Reported Clinical Data
PMID |
Year |
Unaffected |
BrS |
LQT3 |
Other |
Other disease |
13154113 | 1954 | 1 | 1 | 0 | 0 | |
20609320 | 2010 | 0 | 1 | 0 | 0 | |
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.
A2T 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 |
Damaging |
0.001 |
-2.2 |
probablydamaging |
0.997 |
2.305 |
-4.14 |
-1 |
0.728 |
A2T has 16 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 |
1 |
3.8 |
|
3 |
3.8 |
|
4 |
5.4 |
|
5 |
6.6 |
|
6 |
7.6 |
|
7 |
8.5 |
|
8 |
9.3 |
R8Q |
9 |
10.1 |
G9S |
10 |
10.7 |
|
11 |
11.4 |
|
12 |
12 |
|
13 |
12.6 |
|
14 |
13.2 |
R14C R14H |
15 |
13.7 |
R15G R15M R15T |
16 |
14.2 |
|
17 |
14.7 |
|