Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32751 | 98476;98477;98478 | chr2:178539814;178539813;178539812 | chr2:179404541;179404540;179404539 |
| N2AB | 31110 | 93553;93554;93555 | chr2:178539814;178539813;178539812 | chr2:179404541;179404540;179404539 |
| N2A | 30183 | 90772;90773;90774 | chr2:178539814;178539813;178539812 | chr2:179404541;179404540;179404539 |
| N2B | 23686 | 71281;71282;71283 | chr2:178539814;178539813;178539812 | chr2:179404541;179404540;179404539 |
| Novex-1 | 23811 | 71656;71657;71658 | chr2:178539814;178539813;178539812 | chr2:179404541;179404540;179404539 |
| Novex-2 | 23878 | 71857;71858;71859 | chr2:178539814;178539813;178539812 | chr2:179404541;179404540;179404539 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs746586029  |
-1.3 | 1.0 | N | 0.672 | 0.529 | 0.848484510922 | gnomAD-2.1.1 | 1.78E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 3.12E-05 | 0 |
| I/T | rs746586029 |
-1.3 | 1.0 | N | 0.672 | 0.529 | 0.848484510922 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | I | None | 7.24E-05 | 0 | 0 | 0 | 1.92976E-04 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/T | rs746586029 |
-1.3 | 1.0 | N | 0.672 | 0.529 | 0.848484510922 | gnomAD-4.0.0 | 3.71817E-05 | None | None | None | None | I | None | 5.34088E-05 | 0 | None | 0 | 2.22836E-05 | None | 0 | 0 | 4.32283E-05 | 1.09784E-05 | 4.80277E-05 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.639 | likely_pathogenic | 0.6967 | pathogenic | -1.369 | Destabilizing | 0.999 | D | 0.483 | neutral | None | None | None | None | I |
| I/C | 0.9255 | likely_pathogenic | 0.9394 | pathogenic | -0.914 | Destabilizing | 1.0 | D | 0.718 | prob.delet. | None | None | None | None | I |
| I/D | 0.9726 | likely_pathogenic | 0.9808 | pathogenic | -0.475 | Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | I |
| I/E | 0.8768 | likely_pathogenic | 0.9093 | pathogenic | -0.451 | Destabilizing | 1.0 | D | 0.778 | deleterious | None | None | None | None | I |
| I/F | 0.3081 | likely_benign | 0.3522 | ambiguous | -0.864 | Destabilizing | 1.0 | D | 0.691 | prob.neutral | N | 0.490153463 | None | None | I |
| I/G | 0.9441 | likely_pathogenic | 0.9583 | pathogenic | -1.696 | Destabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | I |
| I/H | 0.8882 | likely_pathogenic | 0.9183 | pathogenic | -0.826 | Destabilizing | 1.0 | D | 0.793 | deleterious | None | None | None | None | I |
| I/K | 0.7695 | likely_pathogenic | 0.8181 | pathogenic | -0.805 | Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | I |
| I/L | 0.1914 | likely_benign | 0.2289 | benign | -0.55 | Destabilizing | 0.993 | D | 0.385 | neutral | N | 0.486061631 | None | None | I |
| I/M | 0.161 | likely_benign | 0.1771 | benign | -0.56 | Destabilizing | 1.0 | D | 0.705 | prob.neutral | N | 0.499672889 | None | None | I |
| I/N | 0.8053 | likely_pathogenic | 0.8521 | pathogenic | -0.708 | Destabilizing | 1.0 | D | 0.794 | deleterious | D | 0.538669784 | None | None | I |
| I/P | 0.9613 | likely_pathogenic | 0.9719 | pathogenic | -0.791 | Destabilizing | 1.0 | D | 0.798 | deleterious | None | None | None | None | I |
| I/Q | 0.8095 | likely_pathogenic | 0.8493 | pathogenic | -0.804 | Destabilizing | 1.0 | D | 0.783 | deleterious | None | None | None | None | I |
| I/R | 0.7119 | likely_pathogenic | 0.7675 | pathogenic | -0.325 | Destabilizing | 1.0 | D | 0.799 | deleterious | None | None | None | None | I |
| I/S | 0.7762 | likely_pathogenic | 0.8231 | pathogenic | -1.365 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | N | 0.508284171 | None | None | I |
| I/T | 0.3917 | ambiguous | 0.3121 | benign | -1.209 | Destabilizing | 1.0 | D | 0.672 | neutral | N | 0.493952124 | None | None | I |
| I/V | 0.1232 | likely_benign | 0.1343 | benign | -0.791 | Destabilizing | 0.993 | D | 0.38 | neutral | N | 0.492786215 | None | None | I |
| I/W | 0.9109 | likely_pathogenic | 0.9319 | pathogenic | -0.927 | Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | I |
| I/Y | 0.7872 | likely_pathogenic | 0.8242 | pathogenic | -0.68 | Destabilizing | 1.0 | D | 0.724 | prob.delet. | None | None | None | None | I |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.