A735E Summary

SCN5A A735E was found in 3 papers (see below) with a total of 2 carriers: 2 had BrS1, 0 had LQT3, and 0 had other disease. A735E is not present in gnomAD. A735E has been functionally characterized in 1 paper. Other variants at the same resdue are A735E .A735G .A735P .A735S .A735T .A735V . Given the functional data available, we estimate this variant has "LOF" in vitro character. (LOF and GOF denote loss-of-function and gain-of-function, respectively). This residue is located in a Hotspot region for BrS1 and in a Non_Hotspot region for Long QT syndrome.

A735E Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
1190104620020100
2132146520110100
3253394620200000
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

A735E 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 0.9 NA

A735E 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 -4.62 benign 0.004 0.4284 -2.37 -2 0.947

A735E has 56 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
726 14.6
727 12.6
728 10.4 V728I
729 10.2
730 8.9
731 6.3
732 5.4
733 7 F733L F733L F733L
734 5.4
736 4.5
737 6.2
738 9.7
739 13.6
740 14.2
741 11.9
742 14
745 11.4
746 14.2 E746K
748 11.6
749 9.4
750 14.5
752 12.6 G752R G752R
753 12.1
756 13.8
808 12.6 R808C
809 14.1
811 11.5 R811H
812 10.8
814 13 R814Q
815 11.4
818 14.4
1342 12.2
1343 12.4
1345 14.2 W1345C W1345C
1346 8.1 L1346P
1347 10.8
1348 13.4
1349 8.4
1350 6.3
1351 11.9
1352 11
1353 8.3 V1353M
1354 10.2
1355 14.7
1357 12.4 A1357V
1401 14.9
1402 12.8
1403 12.1
1404 8.7
1405 6 V1405L V1405L V1405M
1406 9.7 G1406E G1406R G1406R
1407 11.7
1408 11.2 G1408R G1408R
1409 12
1410 14.7
1412 14.7