Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15280 | 46063;46064;46065 | chr2:178620772;178620771;178620770 | chr2:179485499;179485498;179485497 |
| N2AB | 13639 | 41140;41141;41142 | chr2:178620772;178620771;178620770 | chr2:179485499;179485498;179485497 |
| N2A | 12712 | 38359;38360;38361 | chr2:178620772;178620771;178620770 | chr2:179485499;179485498;179485497 |
| N2B | 6215 | 18868;18869;18870 | chr2:178620772;178620771;178620770 | chr2:179485499;179485498;179485497 |
| Novex-1 | 6340 | 19243;19244;19245 | chr2:178620772;178620771;178620770 | chr2:179485499;179485498;179485497 |
| Novex-2 | 6407 | 19444;19445;19446 | chr2:178620772;178620771;178620770 | chr2:179485499;179485498;179485497 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/F | rs763279178  |
-0.535 | 0.927 | D | 0.738 | 0.315 | 0.587992605178 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.68E-05 | 0 |
| S/F | rs763279178 |
-0.535 | 0.927 | D | 0.738 | 0.315 | 0.587992605178 | gnomAD-4.0.0 | 3.18677E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.72567E-06 | 0 | 0 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0938 | likely_benign | 0.1041 | benign | -0.766 | Destabilizing | 0.002 | N | 0.239 | neutral | N | 0.509097814 | None | None | N |
| S/C | 0.1045 | likely_benign | 0.1173 | benign | -0.646 | Destabilizing | 0.98 | D | 0.703 | prob.neutral | D | 0.550525758 | None | None | N |
| S/D | 0.5563 | ambiguous | 0.6365 | pathogenic | -1.051 | Destabilizing | 0.543 | D | 0.643 | neutral | None | None | None | None | N |
| S/E | 0.5705 | likely_pathogenic | 0.6392 | pathogenic | -0.942 | Destabilizing | 0.704 | D | 0.638 | neutral | None | None | None | None | N |
| S/F | 0.1432 | likely_benign | 0.1619 | benign | -0.646 | Destabilizing | 0.927 | D | 0.738 | prob.delet. | D | 0.550087358 | None | None | N |
| S/G | 0.1736 | likely_benign | 0.196 | benign | -1.109 | Destabilizing | 0.329 | N | 0.575 | neutral | None | None | None | None | N |
| S/H | 0.3184 | likely_benign | 0.3709 | ambiguous | -1.512 | Destabilizing | 0.944 | D | 0.708 | prob.delet. | None | None | None | None | N |
| S/I | 0.1039 | likely_benign | 0.1271 | benign | 0.072 | Stabilizing | 0.543 | D | 0.71 | prob.delet. | None | None | None | None | N |
| S/K | 0.7565 | likely_pathogenic | 0.8113 | pathogenic | -0.575 | Destabilizing | 0.704 | D | 0.634 | neutral | None | None | None | None | N |
| S/L | 0.0873 | likely_benign | 0.0966 | benign | 0.072 | Stabilizing | 0.329 | N | 0.685 | prob.neutral | None | None | None | None | N |
| S/M | 0.1614 | likely_benign | 0.1848 | benign | 0.144 | Stabilizing | 0.176 | N | 0.556 | neutral | None | None | None | None | N |
| S/N | 0.1465 | likely_benign | 0.1746 | benign | -0.941 | Destabilizing | 0.031 | N | 0.368 | neutral | None | None | None | None | N |
| S/P | 0.9354 | likely_pathogenic | 0.9506 | pathogenic | -0.172 | Destabilizing | 0.927 | D | 0.732 | prob.delet. | D | 0.549919721 | None | None | N |
| S/Q | 0.5104 | ambiguous | 0.5698 | pathogenic | -0.901 | Destabilizing | 0.944 | D | 0.703 | prob.neutral | None | None | None | None | N |
| S/R | 0.6168 | likely_pathogenic | 0.6937 | pathogenic | -0.715 | Destabilizing | 0.828 | D | 0.735 | prob.delet. | None | None | None | None | N |
| S/T | 0.0785 | likely_benign | 0.0843 | benign | -0.748 | Destabilizing | 0.023 | N | 0.245 | neutral | N | 0.466049916 | None | None | N |
| S/V | 0.1377 | likely_benign | 0.1598 | benign | -0.172 | Destabilizing | 0.031 | N | 0.529 | neutral | None | None | None | None | N |
| S/W | 0.3035 | likely_benign | 0.3406 | ambiguous | -0.771 | Destabilizing | 0.995 | D | 0.739 | prob.delet. | None | None | None | None | N |
| S/Y | 0.1394 | likely_benign | 0.1611 | benign | -0.411 | Destabilizing | 0.975 | D | 0.739 | prob.delet. | D | 0.549919721 | None | None | N |
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.