D1370G Summary

SCN5A D1370G was found in 1 paper (see below) with a total of 15 carriers: 0 had BrS1, 0 had LQT3, and 0 had other disease. D1370G is present in 15 out of 251424 alleles in gnomAD (minor allele frequency of 0.005966%). D1370G has been functionally characterized in 1 paper. Other variants at the same resdue are D1370A .D1370E .D1370E .D1370G .D1370H .D1370N .D1370V .D1370Y . Given the functional data available, we estimate this variant has "Normal" in vitro character. (LOF and GOF denote loss-of-function and gain-of-function, respectively). This residue is located in a Non_Hotspot region for BrS1 and in a Non_Hotspot region for Long QT syndrome.

D1370G Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
3253394620200000
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

D1370G 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
32533946 2020 HEK 85.1 6.2 0.8 0.833333333 NA

D1370G 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 0.085 -3.41 benign 0.12 2.455 -1.66 -3 0.698

D1370G 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
1355 14.7
1356 14.2
1357 13.7 A1357V
1358 13.2
1359 12.6
1360 12
1361 11.4
1362 10.7
1363 10.1
1364 9.3
1365 8.5
1366 7.6
1367 6.6
1368 5.4
1369 3.8
1371 3.8
1372 5.4
1373 6.6
1374 7.6
1375 8.5
1376 9.3
1377 10.1
1378 10.7 V1378M
1379 11.4
1380 12 N1380K N1380K p.N1380del
1381 12.6
1382 13.2 S1382I
1383 13.7
1384 14.2
1385 14.7