Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24851 | 74776;74777;74778 | chr2:178571581;178571580;178571579 | chr2:179436308;179436307;179436306 |
| N2AB | 23210 | 69853;69854;69855 | chr2:178571581;178571580;178571579 | chr2:179436308;179436307;179436306 |
| N2A | 22283 | 67072;67073;67074 | chr2:178571581;178571580;178571579 | chr2:179436308;179436307;179436306 |
| N2B | 15786 | 47581;47582;47583 | chr2:178571581;178571580;178571579 | chr2:179436308;179436307;179436306 |
| Novex-1 | 15911 | 47956;47957;47958 | chr2:178571581;178571580;178571579 | chr2:179436308;179436307;179436306 |
| Novex-2 | 15978 | 48157;48158;48159 | chr2:178571581;178571580;178571579 | chr2:179436308;179436307;179436306 |
| 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/I | rs756862019  |
-0.405 | 1.0 | D | 0.667 | 0.455 | 0.40017627803 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.69E-05 | 0 |
| T/I | rs756862019 |
-0.405 | 1.0 | D | 0.667 | 0.455 | 0.40017627803 | 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 |
| T/I | rs756862019 |
-0.405 | 1.0 | D | 0.667 | 0.455 | 0.40017627803 | gnomAD-4.0.0 | 8.05886E-06 | None | None | None | None | N | None | 1.3354E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.01731E-05 | 0 | 0 |
| T/N | None | None | 1.0 | N | 0.717 | 0.336 | 0.36076525451 | gnomAD-4.0.0 | 2.05332E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.6988E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.2118 | likely_benign | 0.2121 | benign | -0.824 | Destabilizing | 0.999 | D | 0.569 | neutral | N | 0.475074741 | None | None | N |
| T/C | 0.7198 | likely_pathogenic | 0.7287 | pathogenic | -0.577 | Destabilizing | 1.0 | D | 0.614 | neutral | None | None | None | None | N |
| T/D | 0.8891 | likely_pathogenic | 0.8843 | pathogenic | -0.745 | Destabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | N |
| T/E | 0.8591 | likely_pathogenic | 0.8569 | pathogenic | -0.759 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | N |
| T/F | 0.8144 | likely_pathogenic | 0.8256 | pathogenic | -1.014 | Destabilizing | 1.0 | D | 0.704 | prob.neutral | None | None | None | None | N |
| T/G | 0.6317 | likely_pathogenic | 0.6186 | pathogenic | -1.055 | Destabilizing | 1.0 | D | 0.666 | neutral | None | None | None | None | N |
| T/H | 0.8023 | likely_pathogenic | 0.8067 | pathogenic | -1.372 | Destabilizing | 1.0 | D | 0.652 | neutral | None | None | None | None | N |
| T/I | 0.4928 | ambiguous | 0.5204 | ambiguous | -0.3 | Destabilizing | 1.0 | D | 0.667 | neutral | D | 0.522444614 | None | None | N |
| T/K | 0.7174 | likely_pathogenic | 0.7222 | pathogenic | -0.805 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | N |
| T/L | 0.2702 | likely_benign | 0.2904 | benign | -0.3 | Destabilizing | 0.999 | D | 0.602 | neutral | None | None | None | None | N |
| T/M | 0.2354 | likely_benign | 0.2444 | benign | 0.149 | Stabilizing | 1.0 | D | 0.621 | neutral | None | None | None | None | N |
| T/N | 0.4661 | ambiguous | 0.4656 | ambiguous | -0.781 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | N | 0.467040372 | None | None | N |
| T/P | 0.5398 | ambiguous | 0.5581 | ambiguous | -0.444 | Destabilizing | 1.0 | D | 0.647 | neutral | N | 0.502146699 | None | None | N |
| T/Q | 0.7509 | likely_pathogenic | 0.7576 | pathogenic | -1.063 | Destabilizing | 1.0 | D | 0.673 | neutral | None | None | None | None | N |
| T/R | 0.641 | likely_pathogenic | 0.643 | pathogenic | -0.461 | Destabilizing | 1.0 | D | 0.663 | neutral | None | None | None | None | N |
| T/S | 0.3017 | likely_benign | 0.2962 | benign | -1.001 | Destabilizing | 0.999 | D | 0.587 | neutral | N | 0.477941688 | None | None | N |
| T/V | 0.3107 | likely_benign | 0.3276 | benign | -0.444 | Destabilizing | 0.999 | D | 0.61 | neutral | None | None | None | None | N |
| T/W | 0.9694 | likely_pathogenic | 0.9709 | pathogenic | -0.937 | Destabilizing | 1.0 | D | 0.665 | neutral | None | None | None | None | N |
| T/Y | 0.8537 | likely_pathogenic | 0.8645 | pathogenic | -0.693 | Destabilizing | 1.0 | D | 0.691 | prob.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.