Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 5777 | 17554;17555;17556 | chr2:178731437;178731436;178731435 | chr2:179596164;179596163;179596162 |
| N2AB | 5460 | 16603;16604;16605 | chr2:178731437;178731436;178731435 | chr2:179596164;179596163;179596162 |
| N2A | 4533 | 13822;13823;13824 | chr2:178731437;178731436;178731435 | chr2:179596164;179596163;179596162 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/G | None | None | 0.081 | N | 0.332 | 0.256 | 0.462111473445 | gnomAD-4.0.0 | 1.59129E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43279E-05 | 0 |
| R/K | rs759657332  |
None | None | N | 0.085 | 0.144 | 0.238096912614 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/K | rs759657332 |
None | None | N | 0.085 | 0.144 | 0.238096912614 | gnomAD-4.0.0 | 2.4789E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.54283E-06 | 1.09801E-05 | 0 |
| R/S | rs367942154 |
-0.511 | 0.003 | N | 0.189 | 0.285 | 0.250039746154 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.55E-05 | 0 |
| R/S | rs367942154 |
-0.511 | 0.003 | N | 0.189 | 0.285 | 0.250039746154 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| R/S | rs367942154 |
-0.511 | 0.003 | N | 0.189 | 0.285 | 0.250039746154 | gnomAD-4.0.0 | 8.05629E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.01713E-05 | 0 | 1.60128E-05 |
| R/T | rs759657332 |
-0.218 | None | N | 0.171 | 0.294 | 0.273503213844 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| R/T | rs759657332 |
-0.218 | None | N | 0.171 | 0.294 | 0.273503213844 | gnomAD-4.0.0 | 6.84215E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15934E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.3359 | likely_benign | 0.3171 | benign | -0.599 | Destabilizing | 0.025 | N | 0.254 | neutral | None | None | None | None | N |
| R/C | 0.2129 | likely_benign | 0.2059 | benign | -0.637 | Destabilizing | 0.667 | D | 0.369 | neutral | None | None | None | None | N |
| R/D | 0.6006 | likely_pathogenic | 0.5944 | pathogenic | 0.134 | Stabilizing | 0.104 | N | 0.365 | neutral | None | None | None | None | N |
| R/E | 0.287 | likely_benign | 0.2718 | benign | 0.247 | Stabilizing | 0.025 | N | 0.167 | neutral | None | None | None | None | N |
| R/F | 0.4653 | ambiguous | 0.4431 | ambiguous | -0.607 | Destabilizing | 0.667 | D | 0.416 | neutral | None | None | None | None | N |
| R/G | 0.2475 | likely_benign | 0.2493 | benign | -0.87 | Destabilizing | 0.081 | N | 0.332 | neutral | N | 0.501987276 | None | None | N |
| R/H | 0.0961 | likely_benign | 0.0931 | benign | -1.258 | Destabilizing | 0.667 | D | 0.314 | neutral | None | None | None | None | N |
| R/I | 0.213 | likely_benign | 0.1961 | benign | 0.11 | Stabilizing | 0.096 | N | 0.487 | neutral | N | 0.479265132 | None | None | N |
| R/K | 0.0815 | likely_benign | 0.0799 | benign | -0.459 | Destabilizing | None | N | 0.085 | neutral | N | 0.420560758 | None | None | N |
| R/L | 0.2143 | likely_benign | 0.2062 | benign | 0.11 | Stabilizing | 0.055 | N | 0.325 | neutral | None | None | None | None | N |
| R/M | 0.2162 | likely_benign | 0.2047 | benign | -0.291 | Destabilizing | 0.667 | D | 0.359 | neutral | None | None | None | None | N |
| R/N | 0.4683 | ambiguous | 0.4502 | ambiguous | -0.099 | Destabilizing | 0.104 | N | 0.249 | neutral | None | None | None | None | N |
| R/P | 0.8784 | likely_pathogenic | 0.8873 | pathogenic | -0.105 | Destabilizing | 0.364 | N | 0.46 | neutral | None | None | None | None | N |
| R/Q | 0.0889 | likely_benign | 0.088 | benign | -0.234 | Destabilizing | 0.005 | N | 0.104 | neutral | None | None | None | None | N |
| R/S | 0.3491 | ambiguous | 0.3435 | ambiguous | -0.808 | Destabilizing | 0.003 | N | 0.189 | neutral | N | 0.460657941 | None | None | N |
| R/T | 0.1688 | likely_benign | 0.1495 | benign | -0.517 | Destabilizing | None | N | 0.171 | neutral | N | 0.439341307 | None | None | N |
| R/V | 0.2818 | likely_benign | 0.2611 | benign | -0.105 | Destabilizing | 0.055 | N | 0.375 | neutral | None | None | None | None | N |
| R/W | 0.1719 | likely_benign | 0.1717 | benign | -0.39 | Destabilizing | 0.958 | D | 0.378 | neutral | None | None | None | None | N |
| R/Y | 0.3631 | ambiguous | 0.346 | ambiguous | -0.05 | Destabilizing | 0.667 | D | 0.437 | 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.