Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16067 | 48424;48425;48426 | chr2:178616592;178616591;178616590 | chr2:179481319;179481318;179481317 |
| N2AB | 14426 | 43501;43502;43503 | chr2:178616592;178616591;178616590 | chr2:179481319;179481318;179481317 |
| N2A | 13499 | 40720;40721;40722 | chr2:178616592;178616591;178616590 | chr2:179481319;179481318;179481317 |
| N2B | 7002 | 21229;21230;21231 | chr2:178616592;178616591;178616590 | chr2:179481319;179481318;179481317 |
| Novex-1 | 7127 | 21604;21605;21606 | chr2:178616592;178616591;178616590 | chr2:179481319;179481318;179481317 |
| Novex-2 | 7194 | 21805;21806;21807 | chr2:178616592;178616591;178616590 | chr2:179481319;179481318;179481317 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/K | None | None | 0.055 | N | 0.451 | 0.318 | 0.767110480819 | gnomAD-4.0.0 | 1.36952E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79999E-06 | 0 | 0 |
| I/R | rs2057385323  |
None | 0.295 | N | 0.445 | 0.353 | 0.794207813746 | 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 |
| I/R | rs2057385323 |
None | 0.295 | N | 0.445 | 0.353 | 0.794207813746 | gnomAD-4.0.0 | 6.58458E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47301E-05 | 0 | 0 |
| I/T | rs2057385323 |
None | 0.012 | N | 0.365 | 0.203 | 0.587933254401 | gnomAD-4.0.0 | 1.36952E-06 | None | None | None | None | N | None | 0 | 0 | None | 3.83318E-05 | 0 | None | 0 | 0 | 8.99996E-07 | 0 | 0 |
| I/V | rs1272100018 |
None | None | N | 0.095 | 0.068 | 0.231873229951 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 4.65E-05 | 0 | 0 |
| I/V | rs1272100018 |
None | None | N | 0.095 | 0.068 | 0.231873229951 | gnomAD-4.0.0 | 1.59426E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.88331E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.2774 | likely_benign | 0.3415 | ambiguous | -1.663 | Destabilizing | None | N | 0.136 | neutral | None | None | None | None | N |
| I/C | 0.507 | ambiguous | 0.5877 | pathogenic | -1.183 | Destabilizing | 0.356 | N | 0.327 | neutral | None | None | None | None | N |
| I/D | 0.7333 | likely_pathogenic | 0.7942 | pathogenic | -1.062 | Destabilizing | 0.356 | N | 0.458 | neutral | None | None | None | None | N |
| I/E | 0.5808 | likely_pathogenic | 0.655 | pathogenic | -1.07 | Destabilizing | 0.072 | N | 0.441 | neutral | None | None | None | None | N |
| I/F | 0.1699 | likely_benign | 0.186 | benign | -1.382 | Destabilizing | 0.072 | N | 0.336 | neutral | None | None | None | None | N |
| I/G | 0.5873 | likely_pathogenic | 0.6792 | pathogenic | -1.974 | Destabilizing | 0.038 | N | 0.417 | neutral | None | None | None | None | N |
| I/H | 0.5255 | ambiguous | 0.5831 | pathogenic | -1.336 | Destabilizing | 0.864 | D | 0.381 | neutral | None | None | None | None | N |
| I/K | 0.3471 | ambiguous | 0.4241 | ambiguous | -1.008 | Destabilizing | 0.055 | N | 0.451 | neutral | N | 0.478394945 | None | None | N |
| I/L | 0.1072 | likely_benign | 0.119 | benign | -0.887 | Destabilizing | None | N | 0.074 | neutral | N | 0.481378173 | None | None | N |
| I/M | 0.0934 | likely_benign | 0.1014 | benign | -0.718 | Destabilizing | 0.171 | N | 0.373 | neutral | N | 0.50770882 | None | None | N |
| I/N | 0.3201 | likely_benign | 0.367 | ambiguous | -0.797 | Destabilizing | 0.356 | N | 0.439 | neutral | None | None | None | None | N |
| I/P | 0.6575 | likely_pathogenic | 0.7501 | pathogenic | -1.115 | Destabilizing | 0.356 | N | 0.452 | neutral | None | None | None | None | N |
| I/Q | 0.4253 | ambiguous | 0.4962 | ambiguous | -1.001 | Destabilizing | 0.356 | N | 0.423 | neutral | None | None | None | None | N |
| I/R | 0.2983 | likely_benign | 0.3547 | ambiguous | -0.5 | Destabilizing | 0.295 | N | 0.445 | neutral | N | 0.498753421 | None | None | N |
| I/S | 0.3116 | likely_benign | 0.3668 | ambiguous | -1.435 | Destabilizing | 0.038 | N | 0.361 | neutral | None | None | None | None | N |
| I/T | 0.1998 | likely_benign | 0.2418 | benign | -1.322 | Destabilizing | 0.012 | N | 0.365 | neutral | N | 0.485581772 | None | None | N |
| I/V | 0.0609 | likely_benign | 0.0647 | benign | -1.115 | Destabilizing | None | N | 0.095 | neutral | N | 0.402160813 | None | None | N |
| I/W | 0.7688 | likely_pathogenic | 0.8063 | pathogenic | -1.425 | Destabilizing | 0.864 | D | 0.428 | neutral | None | None | None | None | N |
| I/Y | 0.4827 | ambiguous | 0.536 | ambiguous | -1.171 | Destabilizing | 0.356 | N | 0.389 | 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.