Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 5774 | 17545;17546;17547 | chr2:178731446;178731445;178731444 | chr2:179596173;179596172;179596171 |
| N2AB | 5457 | 16594;16595;16596 | chr2:178731446;178731445;178731444 | chr2:179596173;179596172;179596171 |
| N2A | 4530 | 13813;13814;13815 | chr2:178731446;178731445;178731444 | chr2:179596173;179596172;179596171 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/G | None | None | 0.027 | N | 0.279 | 0.099 | 0.126345400529 | gnomAD-4.0.0 | 7.20193E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.87501E-06 | 0 | 0 |
| D/N | rs752660722  |
0.241 | 0.001 | N | 0.149 | 0.077 | None | gnomAD-2.1.1 | 2.5E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.02617E-04 | None | 3.27E-05 | None | 0 | 3.12E-05 | 0 |
| D/N | rs752660722 |
0.241 | 0.001 | N | 0.149 | 0.077 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.93125E-04 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/N | rs752660722 |
0.241 | 0.001 | N | 0.149 | 0.077 | None | gnomAD-4.0.0 | 2.66483E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 4.45812E-05 | None | 0 | 0 | 3.22092E-05 | 3.29381E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.0979 | likely_benign | 0.0973 | benign | 0.029 | Stabilizing | 0.027 | N | 0.273 | neutral | N | 0.489494328 | None | None | N |
| D/C | 0.3773 | ambiguous | 0.3686 | ambiguous | 0.052 | Stabilizing | 0.935 | D | 0.432 | neutral | None | None | None | None | N |
| D/E | 0.096 | likely_benign | 0.0934 | benign | -0.245 | Destabilizing | None | N | 0.154 | neutral | N | 0.414476495 | None | None | N |
| D/F | 0.4113 | ambiguous | 0.4294 | ambiguous | -0.19 | Destabilizing | 0.791 | D | 0.39 | neutral | None | None | None | None | N |
| D/G | 0.0887 | likely_benign | 0.0944 | benign | -0.063 | Destabilizing | 0.027 | N | 0.279 | neutral | N | 0.454994966 | None | None | N |
| D/H | 0.1485 | likely_benign | 0.1488 | benign | 0.316 | Stabilizing | 0.541 | D | 0.292 | neutral | N | 0.495209579 | None | None | N |
| D/I | 0.2106 | likely_benign | 0.2172 | benign | 0.198 | Stabilizing | 0.555 | D | 0.407 | neutral | None | None | None | None | N |
| D/K | 0.1415 | likely_benign | 0.1362 | benign | 0.457 | Stabilizing | 0.081 | N | 0.273 | neutral | None | None | None | None | N |
| D/L | 0.239 | likely_benign | 0.2434 | benign | 0.198 | Stabilizing | 0.38 | N | 0.399 | neutral | None | None | None | None | N |
| D/M | 0.386 | ambiguous | 0.3965 | ambiguous | 0.122 | Stabilizing | 0.935 | D | 0.397 | neutral | None | None | None | None | N |
| D/N | 0.0669 | likely_benign | 0.0697 | benign | 0.397 | Stabilizing | 0.001 | N | 0.149 | neutral | N | 0.468484338 | None | None | N |
| D/P | 0.3851 | ambiguous | 0.3866 | ambiguous | 0.16 | Stabilizing | 0.555 | D | 0.315 | neutral | None | None | None | None | N |
| D/Q | 0.1626 | likely_benign | 0.1563 | benign | 0.368 | Stabilizing | 0.081 | N | 0.28 | neutral | None | None | None | None | N |
| D/R | 0.1647 | likely_benign | 0.163 | benign | 0.595 | Stabilizing | 0.235 | N | 0.363 | neutral | None | None | None | None | N |
| D/S | 0.0791 | likely_benign | 0.0817 | benign | 0.265 | Stabilizing | 0.002 | N | 0.177 | neutral | None | None | None | None | N |
| D/T | 0.1336 | likely_benign | 0.1354 | benign | 0.335 | Stabilizing | 0.081 | N | 0.293 | neutral | None | None | None | None | N |
| D/V | 0.1429 | likely_benign | 0.146 | benign | 0.16 | Stabilizing | 0.317 | N | 0.391 | neutral | N | 0.486398095 | None | None | N |
| D/W | 0.7054 | likely_pathogenic | 0.7029 | pathogenic | -0.19 | Destabilizing | 0.935 | D | 0.505 | neutral | None | None | None | None | N |
| D/Y | 0.1513 | likely_benign | 0.1559 | benign | 0.024 | Stabilizing | 0.879 | D | 0.39 | neutral | N | 0.508946881 | 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.