Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24899 | 74920;74921;74922 | chr2:178571437;178571436;178571435 | chr2:179436164;179436163;179436162 |
| N2AB | 23258 | 69997;69998;69999 | chr2:178571437;178571436;178571435 | chr2:179436164;179436163;179436162 |
| N2A | 22331 | 67216;67217;67218 | chr2:178571437;178571436;178571435 | chr2:179436164;179436163;179436162 |
| N2B | 15834 | 47725;47726;47727 | chr2:178571437;178571436;178571435 | chr2:179436164;179436163;179436162 |
| Novex-1 | 15959 | 48100;48101;48102 | chr2:178571437;178571436;178571435 | chr2:179436164;179436163;179436162 |
| Novex-2 | 16026 | 48301;48302;48303 | chr2:178571437;178571436;178571435 | chr2:179436164;179436163;179436162 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | rs1708138833  |
None | 0.006 | N | 0.405 | 0.198 | 0.481543764896 | 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 |
| P/L | rs1708138833 |
None | 0.006 | N | 0.405 | 0.198 | 0.481543764896 | gnomAD-4.0.0 | 2.56338E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.78826E-06 | 0 | 0 |
| P/T | rs1335200909 |
-0.333 | None | N | 0.171 | 0.114 | 0.215109475489 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| P/T | rs1335200909 |
-0.333 | None | N | 0.171 | 0.114 | 0.215109475489 | gnomAD-4.0.0 | 4.77579E-06 | None | None | None | None | N | None | 0 | 6.86153E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0646 | likely_benign | 0.0613 | benign | -0.772 | Destabilizing | 0.002 | N | 0.299 | neutral | N | 0.452773885 | None | None | N |
| P/C | 0.3154 | likely_benign | 0.2931 | benign | -0.516 | Destabilizing | 0.492 | N | 0.384 | neutral | None | None | None | None | N |
| P/D | 0.5445 | ambiguous | 0.4828 | ambiguous | -0.798 | Destabilizing | 0.015 | N | 0.451 | neutral | None | None | None | None | N |
| P/E | 0.4026 | ambiguous | 0.3446 | ambiguous | -0.922 | Destabilizing | 0.015 | N | 0.397 | neutral | None | None | None | None | N |
| P/F | 0.5536 | ambiguous | 0.5025 | ambiguous | -1.002 | Destabilizing | 0.204 | N | 0.495 | neutral | None | None | None | None | N |
| P/G | 0.2884 | likely_benign | 0.2611 | benign | -0.925 | Destabilizing | 0.007 | N | 0.327 | neutral | None | None | None | None | N |
| P/H | 0.3232 | likely_benign | 0.2953 | benign | -0.49 | Destabilizing | None | N | 0.335 | neutral | N | 0.4703416 | None | None | N |
| P/I | 0.3153 | likely_benign | 0.2815 | benign | -0.51 | Destabilizing | 0.018 | N | 0.589 | neutral | None | None | None | None | N |
| P/K | 0.4596 | ambiguous | 0.4038 | ambiguous | -0.626 | Destabilizing | 0.015 | N | 0.433 | neutral | None | None | None | None | N |
| P/L | 0.1858 | likely_benign | 0.1601 | benign | -0.51 | Destabilizing | 0.006 | N | 0.405 | neutral | N | 0.479923479 | None | None | N |
| P/M | 0.3141 | likely_benign | 0.2764 | benign | -0.296 | Destabilizing | 0.204 | N | 0.418 | neutral | None | None | None | None | N |
| P/N | 0.3279 | likely_benign | 0.2865 | benign | -0.265 | Destabilizing | 0.035 | N | 0.471 | neutral | None | None | None | None | N |
| P/Q | 0.2832 | likely_benign | 0.2496 | benign | -0.6 | Destabilizing | 0.068 | N | 0.549 | neutral | None | None | None | None | N |
| P/R | 0.4003 | ambiguous | 0.3541 | ambiguous | 0.011 | Stabilizing | 0.026 | N | 0.558 | neutral | N | 0.484811777 | None | None | N |
| P/S | 0.1259 | likely_benign | 0.117 | benign | -0.596 | Destabilizing | None | N | 0.176 | neutral | N | 0.473341158 | None | None | N |
| P/T | 0.111 | likely_benign | 0.1042 | benign | -0.632 | Destabilizing | None | N | 0.171 | neutral | N | 0.466667842 | None | None | N |
| P/V | 0.1949 | likely_benign | 0.1777 | benign | -0.562 | Destabilizing | 0.018 | N | 0.451 | neutral | None | None | None | None | N |
| P/W | 0.7269 | likely_pathogenic | 0.6797 | pathogenic | -1.058 | Destabilizing | 0.747 | D | 0.458 | neutral | None | None | None | None | N |
| P/Y | 0.4987 | ambiguous | 0.4451 | ambiguous | -0.775 | Destabilizing | 0.112 | N | 0.547 | 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.