Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31270 | 94033;94034;94035 | chr2:178547818;178547817;178547816 | chr2:179412545;179412544;179412543 |
| N2AB | 29629 | 89110;89111;89112 | chr2:178547818;178547817;178547816 | chr2:179412545;179412544;179412543 |
| N2A | 28702 | 86329;86330;86331 | chr2:178547818;178547817;178547816 | chr2:179412545;179412544;179412543 |
| N2B | 22205 | 66838;66839;66840 | chr2:178547818;178547817;178547816 | chr2:179412545;179412544;179412543 |
| Novex-1 | 22330 | 67213;67214;67215 | chr2:178547818;178547817;178547816 | chr2:179412545;179412544;179412543 |
| Novex-2 | 22397 | 67414;67415;67416 | chr2:178547818;178547817;178547816 | chr2:179412545;179412544;179412543 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/K | rs1280335651  |
None | 0.997 | N | 0.486 | 0.261 | 0.337135696972 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.625E-06 | 0 | 0 |
| R/T | rs1280335651 |
None | 1.0 | N | 0.739 | 0.405 | 0.610711448424 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/T | rs1280335651 |
None | 1.0 | N | 0.739 | 0.405 | 0.610711448424 | gnomAD-4.0.0 | 4.05978E-06 | None | None | None | None | N | None | 1.74697E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 3.61475E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.5301 | ambiguous | 0.5423 | ambiguous | -1.049 | Destabilizing | 0.999 | D | 0.644 | neutral | None | None | None | None | N |
| R/C | 0.1655 | likely_benign | 0.1794 | benign | -1.117 | Destabilizing | 1.0 | D | 0.736 | prob.delet. | None | None | None | None | N |
| R/D | 0.7742 | likely_pathogenic | 0.8109 | pathogenic | -0.672 | Destabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | N |
| R/E | 0.4839 | ambiguous | 0.4844 | ambiguous | -0.574 | Destabilizing | 0.999 | D | 0.637 | neutral | None | None | None | None | N |
| R/F | 0.6328 | likely_pathogenic | 0.6138 | pathogenic | -1.103 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | N |
| R/G | 0.3432 | ambiguous | 0.3883 | ambiguous | -1.33 | Destabilizing | 1.0 | D | 0.71 | prob.delet. | N | 0.485575028 | None | None | N |
| R/H | 0.0987 | likely_benign | 0.1012 | benign | -1.388 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | N |
| R/I | 0.3499 | ambiguous | 0.3444 | ambiguous | -0.294 | Destabilizing | 1.0 | D | 0.762 | deleterious | N | 0.492981003 | None | None | N |
| R/K | 0.1301 | likely_benign | 0.1126 | benign | -1.271 | Destabilizing | 0.997 | D | 0.486 | neutral | N | 0.481763932 | None | None | N |
| R/L | 0.3561 | ambiguous | 0.3617 | ambiguous | -0.294 | Destabilizing | 1.0 | D | 0.71 | prob.delet. | None | None | None | None | N |
| R/M | 0.3395 | likely_benign | 0.3272 | benign | -0.392 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | N |
| R/N | 0.6499 | likely_pathogenic | 0.6449 | pathogenic | -0.738 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | N |
| R/P | 0.9525 | likely_pathogenic | 0.9708 | pathogenic | -0.527 | Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | N |
| R/Q | 0.1181 | likely_benign | 0.1196 | benign | -1.004 | Destabilizing | 1.0 | D | 0.74 | deleterious | None | None | None | None | N |
| R/S | 0.5538 | ambiguous | 0.5698 | pathogenic | -1.478 | Destabilizing | 1.0 | D | 0.747 | deleterious | N | 0.44944087 | None | None | N |
| R/T | 0.2924 | likely_benign | 0.2998 | benign | -1.217 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | N | 0.429065598 | None | None | N |
| R/V | 0.4523 | ambiguous | 0.4359 | ambiguous | -0.527 | Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | N |
| R/W | 0.2449 | likely_benign | 0.2472 | benign | -0.761 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | N |
| R/Y | 0.4727 | ambiguous | 0.4604 | ambiguous | -0.421 | Destabilizing | 1.0 | D | 0.762 | deleterious | 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.