Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2470 | 7633;7634;7635 | chr2:178773648;178773647;178773646 | chr2:179638375;179638374;179638373 |
| N2AB | 2470 | 7633;7634;7635 | chr2:178773648;178773647;178773646 | chr2:179638375;179638374;179638373 |
| N2A | 2470 | 7633;7634;7635 | chr2:178773648;178773647;178773646 | chr2:179638375;179638374;179638373 |
| N2B | 2424 | 7495;7496;7497 | chr2:178773648;178773647;178773646 | chr2:179638375;179638374;179638373 |
| Novex-1 | 2424 | 7495;7496;7497 | chr2:178773648;178773647;178773646 | chr2:179638375;179638374;179638373 |
| Novex-2 | 2424 | 7495;7496;7497 | chr2:178773648;178773647;178773646 | chr2:179638375;179638374;179638373 |
| Novex-3 | 2470 | 7633;7634;7635 | chr2:178773648;178773647;178773646 | chr2:179638375;179638374;179638373 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs1257401940  |
-0.513 | 0.002 | N | 0.134 | 0.257 | 0.460352466543 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| V/A | rs1257401940 |
-0.513 | 0.002 | N | 0.134 | 0.257 | 0.460352466543 | gnomAD-4.0.0 | 1.59071E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43279E-05 | 0 |
| V/F | rs1228257559 |
None | 0.966 | N | 0.443 | 0.391 | 0.822638020212 | gnomAD-4.0.0 | 3.42054E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.49659E-06 | 0 | 0 |
| V/I | rs1228257559 |
None | 0.051 | N | 0.227 | 0.238 | 0.458101713262 | gnomAD-4.0.0 | 5.47287E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.01684E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.3109 | likely_benign | 0.2952 | benign | -0.805 | Destabilizing | 0.002 | N | 0.134 | neutral | N | 0.341709673 | None | None | N |
| V/C | 0.8359 | likely_pathogenic | 0.8224 | pathogenic | -0.814 | Destabilizing | 0.998 | D | 0.443 | neutral | None | None | None | None | N |
| V/D | 0.7406 | likely_pathogenic | 0.7679 | pathogenic | -0.486 | Destabilizing | 0.966 | D | 0.522 | neutral | N | 0.434305814 | None | None | N |
| V/E | 0.5429 | ambiguous | 0.5507 | ambiguous | -0.565 | Destabilizing | 0.949 | D | 0.479 | neutral | None | None | None | None | N |
| V/F | 0.2647 | likely_benign | 0.253 | benign | -0.81 | Destabilizing | 0.966 | D | 0.443 | neutral | N | 0.510168819 | None | None | N |
| V/G | 0.523 | ambiguous | 0.536 | ambiguous | -1.001 | Destabilizing | 0.669 | D | 0.483 | neutral | N | 0.335666585 | None | None | N |
| V/H | 0.7674 | likely_pathogenic | 0.7588 | pathogenic | -0.506 | Destabilizing | 0.998 | D | 0.504 | neutral | None | None | None | None | N |
| V/I | 0.0937 | likely_benign | 0.0863 | benign | -0.418 | Destabilizing | 0.051 | N | 0.227 | neutral | N | 0.501123153 | None | None | N |
| V/K | 0.6088 | likely_pathogenic | 0.6363 | pathogenic | -0.735 | Destabilizing | 0.949 | D | 0.483 | neutral | None | None | None | None | N |
| V/L | 0.2837 | likely_benign | 0.2664 | benign | -0.418 | Destabilizing | 0.454 | N | 0.487 | neutral | N | 0.501123153 | None | None | N |
| V/M | 0.2004 | likely_benign | 0.1843 | benign | -0.432 | Destabilizing | 0.974 | D | 0.47 | neutral | None | None | None | None | N |
| V/N | 0.5342 | ambiguous | 0.5493 | ambiguous | -0.533 | Destabilizing | 0.974 | D | 0.529 | neutral | None | None | None | None | N |
| V/P | 0.9243 | likely_pathogenic | 0.9393 | pathogenic | -0.511 | Destabilizing | 0.974 | D | 0.477 | neutral | None | None | None | None | N |
| V/Q | 0.5183 | ambiguous | 0.517 | ambiguous | -0.747 | Destabilizing | 0.974 | D | 0.481 | neutral | None | None | None | None | N |
| V/R | 0.5657 | likely_pathogenic | 0.5953 | pathogenic | -0.196 | Destabilizing | 0.974 | D | 0.524 | neutral | None | None | None | None | N |
| V/S | 0.3909 | ambiguous | 0.3863 | ambiguous | -0.957 | Destabilizing | 0.728 | D | 0.431 | neutral | None | None | None | None | N |
| V/T | 0.3475 | ambiguous | 0.3447 | ambiguous | -0.928 | Destabilizing | 0.842 | D | 0.384 | neutral | None | None | None | None | N |
| V/W | 0.9396 | likely_pathogenic | 0.9319 | pathogenic | -0.906 | Destabilizing | 0.998 | D | 0.558 | neutral | None | None | None | None | N |
| V/Y | 0.7264 | likely_pathogenic | 0.7193 | pathogenic | -0.616 | Destabilizing | 0.991 | D | 0.453 | 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.