Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28406 | 85441;85442;85443 | chr2:178560916;178560915;178560914 | chr2:179425643;179425642;179425641 |
| N2AB | 26765 | 80518;80519;80520 | chr2:178560916;178560915;178560914 | chr2:179425643;179425642;179425641 |
| N2A | 25838 | 77737;77738;77739 | chr2:178560916;178560915;178560914 | chr2:179425643;179425642;179425641 |
| N2B | 19341 | 58246;58247;58248 | chr2:178560916;178560915;178560914 | chr2:179425643;179425642;179425641 |
| Novex-1 | 19466 | 58621;58622;58623 | chr2:178560916;178560915;178560914 | chr2:179425643;179425642;179425641 |
| Novex-2 | 19533 | 58822;58823;58824 | chr2:178560916;178560915;178560914 | chr2:179425643;179425642;179425641 |
| 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 | rs1559292657  |
None | 0.822 | N | 0.585 | 0.567 | 0.757037788863 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs1559292657 |
None | 0.822 | N | 0.585 | 0.567 | 0.757037788863 | gnomAD-4.0.0 | 1.59134E-06 | None | None | None | None | N | None | 0 | 2.28686E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs1703410550 |
None | 0.058 | N | 0.149 | 0.078 | 0.331876078066 | gnomAD-4.0.0 | 3.18258E-06 | None | None | None | None | N | None | 0 | 4.57352E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.8136 | likely_pathogenic | 0.8044 | pathogenic | -1.918 | Destabilizing | 0.86 | D | 0.501 | neutral | None | None | None | None | N |
| I/C | 0.8647 | likely_pathogenic | 0.851 | pathogenic | -1.39 | Destabilizing | 0.998 | D | 0.62 | neutral | None | None | None | None | N |
| I/D | 0.954 | likely_pathogenic | 0.9504 | pathogenic | -1.014 | Destabilizing | 0.993 | D | 0.739 | prob.delet. | None | None | None | None | N |
| I/E | 0.8791 | likely_pathogenic | 0.8793 | pathogenic | -0.92 | Destabilizing | 0.978 | D | 0.724 | prob.delet. | None | None | None | None | N |
| I/F | 0.3216 | likely_benign | 0.3067 | benign | -1.158 | Destabilizing | 0.942 | D | 0.505 | neutral | N | 0.496572244 | None | None | N |
| I/G | 0.9271 | likely_pathogenic | 0.9226 | pathogenic | -2.338 | Highly Destabilizing | 0.978 | D | 0.716 | prob.delet. | None | None | None | None | N |
| I/H | 0.8309 | likely_pathogenic | 0.8172 | pathogenic | -1.491 | Destabilizing | 0.998 | D | 0.738 | prob.delet. | None | None | None | None | N |
| I/K | 0.6513 | likely_pathogenic | 0.642 | pathogenic | -1.222 | Destabilizing | 0.978 | D | 0.721 | prob.delet. | None | None | None | None | N |
| I/L | 0.2299 | likely_benign | 0.2361 | benign | -0.789 | Destabilizing | 0.006 | N | 0.136 | neutral | N | 0.49593668 | None | None | N |
| I/M | 0.1565 | likely_benign | 0.1523 | benign | -0.785 | Destabilizing | 0.942 | D | 0.519 | neutral | N | 0.494241613 | None | None | N |
| I/N | 0.6555 | likely_pathogenic | 0.6363 | pathogenic | -1.18 | Destabilizing | 0.99 | D | 0.737 | prob.delet. | D | 0.53932812 | None | None | N |
| I/P | 0.9759 | likely_pathogenic | 0.9808 | pathogenic | -1.136 | Destabilizing | 0.993 | D | 0.737 | prob.delet. | None | None | None | None | N |
| I/Q | 0.7782 | likely_pathogenic | 0.771 | pathogenic | -1.221 | Destabilizing | 0.993 | D | 0.732 | prob.delet. | None | None | None | None | N |
| I/R | 0.5914 | likely_pathogenic | 0.5833 | pathogenic | -0.797 | Destabilizing | 0.978 | D | 0.737 | prob.delet. | None | None | None | None | N |
| I/S | 0.7873 | likely_pathogenic | 0.7698 | pathogenic | -1.98 | Destabilizing | 0.97 | D | 0.644 | neutral | D | 0.527211346 | None | None | N |
| I/T | 0.7051 | likely_pathogenic | 0.6801 | pathogenic | -1.746 | Destabilizing | 0.822 | D | 0.585 | neutral | N | 0.515348062 | None | None | N |
| I/V | 0.1397 | likely_benign | 0.1299 | benign | -1.136 | Destabilizing | 0.058 | N | 0.149 | neutral | N | 0.481005068 | None | None | N |
| I/W | 0.8751 | likely_pathogenic | 0.8603 | pathogenic | -1.251 | Destabilizing | 0.998 | D | 0.74 | deleterious | None | None | None | None | N |
| I/Y | 0.6744 | likely_pathogenic | 0.661 | pathogenic | -1.01 | Destabilizing | 0.978 | D | 0.636 | neutral | 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.