Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 6641 | 20146;20147;20148 | chr2:178727657;178727656;178727655 | chr2:179592384;179592383;179592382 |
| N2AB | 6324 | 19195;19196;19197 | chr2:178727657;178727656;178727655 | chr2:179592384;179592383;179592382 |
| N2A | 5397 | 16414;16415;16416 | chr2:178727657;178727656;178727655 | chr2:179592384;179592383;179592382 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | None | None | 0.001 | N | 0.141 | 0.096 | 0.0884992946249 | gnomAD-4.0.0 | 1.5932E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86202E-06 | 0 | 0 |
| T/I | rs747240394  |
None | 0.175 | N | 0.539 | 0.135 | 0.332133492242 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/I | rs747240394 |
None | 0.175 | N | 0.539 | 0.135 | 0.332133492242 | gnomAD-4.0.0 | 6.57601E-06 | None | None | None | None | N | None | 0 | 6.55652E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/N | rs747240394 |
-0.292 | 0.096 | N | 0.467 | 0.089 | 0.262662153117 | gnomAD-2.1.1 | 2.93278E-04 | None | None | None | None | N | None | 0 | 2.26667E-03 | None | 0 | 0 | None | 0 | None | 0 | 0 | 2.81849E-04 |
| T/N | rs747240394 |
-0.292 | 0.096 | N | 0.467 | 0.089 | 0.262662153117 | gnomAD-3.1.2 | 7.23E-05 | None | None | None | None | N | None | 0 | 7.21217E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/N | rs747240394 |
-0.292 | 0.096 | N | 0.467 | 0.089 | 0.262662153117 | gnomAD-4.0.0 | 1.23129E-04 | None | None | None | None | N | None | 0 | 1.61148E-03 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 2.84689E-05 |
| T/P | rs768808788 |
-0.597 | 0.301 | D | 0.544 | 0.259 | 0.321108458156 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.28E-05 | None | 0 | 0 | 0 |
| T/P | rs768808788 |
-0.597 | 0.301 | D | 0.544 | 0.259 | 0.321108458156 | gnomAD-4.0.0 | 1.5932E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43497E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0889 | likely_benign | 0.077 | benign | -0.915 | Destabilizing | 0.001 | N | 0.141 | neutral | N | 0.373980319 | None | None | N |
| T/C | 0.6155 | likely_pathogenic | 0.5302 | ambiguous | -0.544 | Destabilizing | 0.667 | D | 0.534 | neutral | None | None | None | None | N |
| T/D | 0.4912 | ambiguous | 0.4648 | ambiguous | 0.217 | Stabilizing | 0.22 | N | 0.525 | neutral | None | None | None | None | N |
| T/E | 0.3875 | ambiguous | 0.3374 | benign | 0.227 | Stabilizing | 0.055 | N | 0.475 | neutral | None | None | None | None | N |
| T/F | 0.4637 | ambiguous | 0.3775 | ambiguous | -1.025 | Destabilizing | 0.667 | D | 0.564 | neutral | None | None | None | None | N |
| T/G | 0.2629 | likely_benign | 0.2249 | benign | -1.168 | Destabilizing | 0.055 | N | 0.402 | neutral | None | None | None | None | N |
| T/H | 0.3875 | ambiguous | 0.348 | ambiguous | -1.367 | Destabilizing | 0.667 | D | 0.561 | neutral | None | None | None | None | N |
| T/I | 0.3739 | ambiguous | 0.2954 | benign | -0.331 | Destabilizing | 0.175 | N | 0.539 | neutral | N | 0.484593594 | None | None | N |
| T/K | 0.3065 | likely_benign | 0.2661 | benign | -0.496 | Destabilizing | 0.055 | N | 0.441 | neutral | None | None | None | None | N |
| T/L | 0.1907 | likely_benign | 0.1604 | benign | -0.331 | Destabilizing | 0.104 | N | 0.449 | neutral | None | None | None | None | N |
| T/M | 0.1156 | likely_benign | 0.1015 | benign | -0.071 | Destabilizing | 0.859 | D | 0.545 | neutral | None | None | None | None | N |
| T/N | 0.1523 | likely_benign | 0.1389 | benign | -0.468 | Destabilizing | 0.096 | N | 0.467 | neutral | N | 0.48390016 | None | None | N |
| T/P | 0.2515 | likely_benign | 0.2282 | benign | -0.494 | Destabilizing | 0.301 | N | 0.544 | neutral | D | 0.532808828 | None | None | N |
| T/Q | 0.2958 | likely_benign | 0.2594 | benign | -0.616 | Destabilizing | 0.22 | N | 0.541 | neutral | None | None | None | None | N |
| T/R | 0.2306 | likely_benign | 0.2056 | benign | -0.314 | Destabilizing | 0.001 | N | 0.258 | neutral | None | None | None | None | N |
| T/S | 0.1124 | likely_benign | 0.1039 | benign | -0.865 | Destabilizing | None | N | 0.175 | neutral | N | 0.33476857 | None | None | N |
| T/V | 0.2657 | likely_benign | 0.2162 | benign | -0.494 | Destabilizing | 0.104 | N | 0.44 | neutral | None | None | None | None | N |
| T/W | 0.7377 | likely_pathogenic | 0.6946 | pathogenic | -0.905 | Destabilizing | 0.958 | D | 0.571 | neutral | None | None | None | None | N |
| T/Y | 0.4305 | ambiguous | 0.3639 | ambiguous | -0.667 | Destabilizing | 0.859 | D | 0.56 | 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.