Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19935 | 60028;60029;60030 | chr2:178592101;178592100;178592099 | chr2:179456828;179456827;179456826 |
| N2AB | 18294 | 55105;55106;55107 | chr2:178592101;178592100;178592099 | chr2:179456828;179456827;179456826 |
| N2A | 17367 | 52324;52325;52326 | chr2:178592101;178592100;178592099 | chr2:179456828;179456827;179456826 |
| N2B | 10870 | 32833;32834;32835 | chr2:178592101;178592100;178592099 | chr2:179456828;179456827;179456826 |
| Novex-1 | 10995 | 33208;33209;33210 | chr2:178592101;178592100;178592099 | chr2:179456828;179456827;179456826 |
| Novex-2 | 11062 | 33409;33410;33411 | chr2:178592101;178592100;178592099 | chr2:179456828;179456827;179456826 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/G | rs377276874  |
None | 0.999 | N | 0.535 | 0.414 | 0.313518423057 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| S/G | rs377276874 |
None | 0.999 | N | 0.535 | 0.414 | 0.313518423057 | gnomAD-4.0.0 | 1.31565E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.9423E-05 | 0 | 0 |
| S/N | None | None | 0.999 | N | 0.631 | 0.295 | 0.275641507738 | gnomAD-4.0.0 | 2.05355E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69893E-06 | 0 | 0 |
| S/R | None | -0.214 | 1.0 | N | 0.747 | 0.534 | 0.285316908763 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 6.47E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/R | None | -0.214 | 1.0 | N | 0.747 | 0.534 | 0.285316908763 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/R | None | -0.214 | 1.0 | N | 0.747 | 0.534 | 0.285316908763 | gnomAD-4.0.0 | 3.0453E-06 | None | None | None | None | N | None | 5.24366E-05 | 0 | None | 0 | 0 | None | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1623 | likely_benign | 0.1789 | benign | -0.461 | Destabilizing | 0.998 | D | 0.467 | neutral | None | None | None | None | N |
| S/C | 0.1745 | likely_benign | 0.1853 | benign | -0.026 | Destabilizing | 1.0 | D | 0.779 | deleterious | N | 0.472185841 | None | None | N |
| S/D | 0.8549 | likely_pathogenic | 0.8957 | pathogenic | -0.75 | Destabilizing | 0.999 | D | 0.651 | neutral | None | None | None | None | N |
| S/E | 0.8694 | likely_pathogenic | 0.9179 | pathogenic | -0.572 | Destabilizing | 0.999 | D | 0.635 | neutral | None | None | None | None | N |
| S/F | 0.4809 | ambiguous | 0.5735 | pathogenic | -0.32 | Destabilizing | 1.0 | D | 0.815 | deleterious | None | None | None | None | N |
| S/G | 0.2396 | likely_benign | 0.2649 | benign | -0.849 | Destabilizing | 0.999 | D | 0.535 | neutral | N | 0.488199727 | None | None | N |
| S/H | 0.6185 | likely_pathogenic | 0.6981 | pathogenic | -1.133 | Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | N |
| S/I | 0.4249 | ambiguous | 0.5045 | ambiguous | 0.521 | Stabilizing | 1.0 | D | 0.767 | deleterious | N | 0.479654579 | None | None | N |
| S/K | 0.9424 | likely_pathogenic | 0.9611 | pathogenic | 0.065 | Stabilizing | 0.999 | D | 0.64 | neutral | None | None | None | None | N |
| S/L | 0.3179 | likely_benign | 0.3659 | ambiguous | 0.521 | Stabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | N |
| S/M | 0.3356 | likely_benign | 0.3887 | ambiguous | 0.396 | Stabilizing | 1.0 | D | 0.786 | deleterious | None | None | None | None | N |
| S/N | 0.3644 | ambiguous | 0.4271 | ambiguous | -0.515 | Destabilizing | 0.999 | D | 0.631 | neutral | N | 0.48995098 | None | None | N |
| S/P | 0.944 | likely_pathogenic | 0.9622 | pathogenic | 0.228 | Stabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | N |
| S/Q | 0.7453 | likely_pathogenic | 0.8046 | pathogenic | -0.274 | Destabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | N |
| S/R | 0.9133 | likely_pathogenic | 0.9397 | pathogenic | -0.299 | Destabilizing | 1.0 | D | 0.747 | deleterious | N | 0.518001586 | None | None | N |
| S/T | 0.1429 | likely_benign | 0.1589 | benign | -0.257 | Destabilizing | 0.999 | D | 0.513 | neutral | N | 0.484907733 | None | None | N |
| S/V | 0.3841 | ambiguous | 0.4468 | ambiguous | 0.228 | Stabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | None | N |
| S/W | 0.5968 | likely_pathogenic | 0.6772 | pathogenic | -0.622 | Destabilizing | 1.0 | D | 0.814 | deleterious | None | None | None | None | N |
| S/Y | 0.3919 | ambiguous | 0.4706 | ambiguous | -0.128 | Destabilizing | 1.0 | D | 0.822 | deleterious | 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.