Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2318 | 7177;7178;7179 | chr2:178774312;178774311;178774310 | chr2:179639039;179639038;179639037 |
| N2AB | 2318 | 7177;7178;7179 | chr2:178774312;178774311;178774310 | chr2:179639039;179639038;179639037 |
| N2A | 2318 | 7177;7178;7179 | chr2:178774312;178774311;178774310 | chr2:179639039;179639038;179639037 |
| N2B | 2272 | 7039;7040;7041 | chr2:178774312;178774311;178774310 | chr2:179639039;179639038;179639037 |
| Novex-1 | 2272 | 7039;7040;7041 | chr2:178774312;178774311;178774310 | chr2:179639039;179639038;179639037 |
| Novex-2 | 2272 | 7039;7040;7041 | chr2:178774312;178774311;178774310 | chr2:179639039;179639038;179639037 |
| Novex-3 | 2318 | 7177;7178;7179 | chr2:178774312;178774311;178774310 | chr2:179639039;179639038;179639037 |
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/C | rs1487336498  |
-0.214 | 1.0 | N | 0.754 | 0.368 | 0.421184727016 | gnomAD-2.1.1 | 7.97E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.44E-05 | None | 0 | None | 0 | 8.83E-06 | 0 |
| R/C | rs1487336498 |
-0.214 | 1.0 | N | 0.754 | 0.368 | 0.421184727016 | gnomAD-4.0.0 | 2.05225E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69797E-06 | 0 | 0 |
| R/H | rs761566436 |
-0.973 | 1.0 | N | 0.767 | 0.459 | None | gnomAD-2.1.1 | 4.96E-05 | None | None | None | None | N | None | 8.01E-05 | 0 | None | 0 | 0 | None | 2.61301E-04 | None | 0 | 3.11E-05 | 0 |
| R/H | rs761566436 |
-0.973 | 1.0 | N | 0.767 | 0.459 | None | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 1.92234E-04 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| R/H | rs761566436 |
-0.973 | 1.0 | N | 0.767 | 0.459 | None | gnomAD-4.0.0 | 4.33728E-05 | None | None | None | None | N | None | 2.67065E-05 | 0 | None | 0 | 2.45E-04 | None | 0 | 1.64366E-04 | 2.8814E-05 | 2.41551E-04 | 0 |
| R/L | None | None | 1.0 | N | 0.578 | 0.502 | 0.39798585902 | gnomAD-4.0.0 | 1.36817E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.31863E-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 | 0.7554 | likely_pathogenic | 0.8028 | pathogenic | 0.057 | Stabilizing | 0.999 | D | 0.579 | neutral | None | None | None | None | N |
| R/C | 0.4839 | ambiguous | 0.6009 | pathogenic | -0.189 | Destabilizing | 1.0 | D | 0.754 | deleterious | N | 0.453246956 | None | None | N |
| R/D | 0.8864 | likely_pathogenic | 0.9083 | pathogenic | -0.305 | Destabilizing | 1.0 | D | 0.671 | neutral | None | None | None | None | N |
| R/E | 0.7132 | likely_pathogenic | 0.7739 | pathogenic | -0.259 | Destabilizing | 0.999 | D | 0.615 | neutral | None | None | None | None | N |
| R/F | 0.7949 | likely_pathogenic | 0.8474 | pathogenic | -0.226 | Destabilizing | 1.0 | D | 0.724 | prob.delet. | None | None | None | None | N |
| R/G | 0.4999 | ambiguous | 0.5559 | ambiguous | -0.097 | Destabilizing | 1.0 | D | 0.578 | neutral | N | 0.298949225 | None | None | N |
| R/H | 0.2453 | likely_benign | 0.2866 | benign | -0.604 | Destabilizing | 1.0 | D | 0.767 | deleterious | N | 0.447323033 | None | None | N |
| R/I | 0.6742 | likely_pathogenic | 0.7282 | pathogenic | 0.421 | Stabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | N |
| R/K | 0.2373 | likely_benign | 0.258 | benign | -0.138 | Destabilizing | 0.998 | D | 0.507 | neutral | None | None | None | None | N |
| R/L | 0.5771 | likely_pathogenic | 0.6318 | pathogenic | 0.421 | Stabilizing | 1.0 | D | 0.578 | neutral | N | 0.443667889 | None | None | N |
| R/M | 0.6344 | likely_pathogenic | 0.7018 | pathogenic | -0.026 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | N |
| R/N | 0.8272 | likely_pathogenic | 0.8514 | pathogenic | -0.005 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | N |
| R/P | 0.8517 | likely_pathogenic | 0.8752 | pathogenic | 0.318 | Stabilizing | 1.0 | D | 0.675 | prob.neutral | N | 0.447743643 | None | None | N |
| R/Q | 0.2425 | likely_benign | 0.2736 | benign | -0.058 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | N |
| R/S | 0.8204 | likely_pathogenic | 0.851 | pathogenic | -0.195 | Destabilizing | 1.0 | D | 0.639 | neutral | N | 0.428013819 | None | None | N |
| R/T | 0.7303 | likely_pathogenic | 0.774 | pathogenic | -0.039 | Destabilizing | 1.0 | D | 0.639 | neutral | None | None | None | None | N |
| R/V | 0.7697 | likely_pathogenic | 0.8135 | pathogenic | 0.318 | Stabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | N |
| R/W | 0.348 | ambiguous | 0.4338 | ambiguous | -0.382 | Destabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | N |
| R/Y | 0.6318 | likely_pathogenic | 0.6944 | pathogenic | 0.022 | Stabilizing | 1.0 | D | 0.711 | prob.delet. | 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.