Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24613 | 74062;74063;74064 | chr2:178572295;178572294;178572293 | chr2:179437022;179437021;179437020 |
| N2AB | 22972 | 69139;69140;69141 | chr2:178572295;178572294;178572293 | chr2:179437022;179437021;179437020 |
| N2A | 22045 | 66358;66359;66360 | chr2:178572295;178572294;178572293 | chr2:179437022;179437021;179437020 |
| N2B | 15548 | 46867;46868;46869 | chr2:178572295;178572294;178572293 | chr2:179437022;179437021;179437020 |
| Novex-1 | 15673 | 47242;47243;47244 | chr2:178572295;178572294;178572293 | chr2:179437022;179437021;179437020 |
| Novex-2 | 15740 | 47443;47444;47445 | chr2:178572295;178572294;178572293 | chr2:179437022;179437021;179437020 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/P | rs775856841  |
-1.267 | 0.998 | N | 0.69 | 0.204 | 0.360961692134 | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 6.55E-05 | None | 0 | 0 | 0 |
| A/P | rs775856841 |
-1.267 | 0.998 | N | 0.69 | 0.204 | 0.360961692134 | gnomAD-4.0.0 | 2.73989E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 4.64005E-05 | 0 |
| A/T | rs775856841 |
None | 0.863 | N | 0.495 | 0.217 | 0.271763555656 | gnomAD-4.0.0 | 2.05492E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.70141E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.6614 | likely_pathogenic | 0.5871 | pathogenic | -1.782 | Destabilizing | 0.877 | D | 0.573 | neutral | None | None | None | None | N |
| A/D | 0.9909 | likely_pathogenic | 0.9788 | pathogenic | -2.626 | Highly Destabilizing | 0.995 | D | 0.679 | prob.neutral | None | None | None | None | N |
| A/E | 0.9796 | likely_pathogenic | 0.9549 | pathogenic | -2.583 | Highly Destabilizing | 0.985 | D | 0.622 | neutral | N | 0.501862394 | None | None | N |
| A/F | 0.9026 | likely_pathogenic | 0.7959 | pathogenic | -1.097 | Destabilizing | 0.929 | D | 0.681 | prob.neutral | None | None | None | None | N |
| A/G | 0.5849 | likely_pathogenic | 0.4503 | ambiguous | -1.326 | Destabilizing | 0.13 | N | 0.557 | neutral | N | 0.475617838 | None | None | N |
| A/H | 0.9917 | likely_pathogenic | 0.9826 | pathogenic | -1.29 | Destabilizing | 1.0 | D | 0.624 | neutral | None | None | None | None | N |
| A/I | 0.2149 | likely_benign | 0.1538 | benign | -0.413 | Destabilizing | 0.051 | N | 0.285 | neutral | None | None | None | None | N |
| A/K | 0.9949 | likely_pathogenic | 0.9876 | pathogenic | -1.277 | Destabilizing | 0.996 | D | 0.631 | neutral | None | None | None | None | N |
| A/L | 0.4279 | ambiguous | 0.29 | benign | -0.413 | Destabilizing | 0.252 | N | 0.446 | neutral | None | None | None | None | N |
| A/M | 0.5644 | likely_pathogenic | 0.4022 | ambiguous | -0.742 | Destabilizing | 0.929 | D | 0.698 | prob.delet. | None | None | None | None | N |
| A/N | 0.9394 | likely_pathogenic | 0.8885 | pathogenic | -1.446 | Destabilizing | 0.987 | D | 0.723 | deleterious | None | None | None | None | N |
| A/P | 0.6588 | likely_pathogenic | 0.5258 | ambiguous | -0.589 | Destabilizing | 0.998 | D | 0.69 | prob.delet. | N | 0.519841452 | None | None | N |
| A/Q | 0.9709 | likely_pathogenic | 0.9442 | pathogenic | -1.602 | Destabilizing | 1.0 | D | 0.699 | prob.delet. | None | None | None | None | N |
| A/R | 0.9856 | likely_pathogenic | 0.9726 | pathogenic | -0.995 | Destabilizing | 0.999 | D | 0.675 | prob.neutral | None | None | None | None | N |
| A/S | 0.3277 | likely_benign | 0.2668 | benign | -1.721 | Destabilizing | 0.633 | D | 0.534 | neutral | N | 0.47873171 | None | None | N |
| A/T | 0.2886 | likely_benign | 0.192 | benign | -1.591 | Destabilizing | 0.863 | D | 0.495 | neutral | N | 0.475617838 | None | None | N |
| A/V | 0.0836 | likely_benign | 0.0612 | benign | -0.589 | Destabilizing | 0.001 | N | 0.081 | neutral | N | 0.458737065 | None | None | N |
| A/W | 0.996 | likely_pathogenic | 0.9903 | pathogenic | -1.492 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | N |
| A/Y | 0.9763 | likely_pathogenic | 0.9501 | pathogenic | -1.047 | Destabilizing | 0.999 | D | 0.69 | prob.delet. | None | None | 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.