Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16613 | 50062;50063;50064 | chr2:178612884;178612883;178612882 | chr2:179477611;179477610;179477609 |
| N2AB | 14972 | 45139;45140;45141 | chr2:178612884;178612883;178612882 | chr2:179477611;179477610;179477609 |
| N2A | 14045 | 42358;42359;42360 | chr2:178612884;178612883;178612882 | chr2:179477611;179477610;179477609 |
| N2B | 7548 | 22867;22868;22869 | chr2:178612884;178612883;178612882 | chr2:179477611;179477610;179477609 |
| Novex-1 | 7673 | 23242;23243;23244 | chr2:178612884;178612883;178612882 | chr2:179477611;179477610;179477609 |
| Novex-2 | 7740 | 23443;23444;23445 | chr2:178612884;178612883;178612882 | chr2:179477611;179477610;179477609 |
| 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/A | rs1468557688  |
-0.688 | 0.005 | N | 0.317 | 0.111 | 0.117506650769 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.49E-05 | 0 |
| P/A | rs1468557688 |
-0.688 | 0.005 | N | 0.317 | 0.111 | 0.117506650769 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| P/A | rs1468557688 |
-0.688 | 0.005 | N | 0.317 | 0.111 | 0.117506650769 | gnomAD-4.0.0 | 5.58175E-06 | None | None | None | None | N | None | 0 | 1.66973E-05 | None | 0 | 0 | None | 0 | 0 | 6.78405E-06 | 0 | 0 |
| P/S | None | None | 0.012 | N | 0.361 | 0.109 | 0.0954503805726 | gnomAD-4.0.0 | 6.8468E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15974E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0803 | likely_benign | 0.0805 | benign | -0.512 | Destabilizing | 0.005 | N | 0.317 | neutral | N | 0.466575183 | None | None | N |
| P/C | 0.4544 | ambiguous | 0.4327 | ambiguous | -0.696 | Destabilizing | 0.676 | D | 0.489 | neutral | None | None | None | None | N |
| P/D | 0.2777 | likely_benign | 0.3568 | ambiguous | 0.004 | Stabilizing | 0.031 | N | 0.386 | neutral | None | None | None | None | N |
| P/E | 0.1761 | likely_benign | 0.2212 | benign | -0.082 | Destabilizing | 0.007 | N | 0.339 | neutral | None | None | None | None | N |
| P/F | 0.4624 | ambiguous | 0.4554 | ambiguous | -0.581 | Destabilizing | 0.356 | N | 0.501 | neutral | None | None | None | None | N |
| P/G | 0.2024 | likely_benign | 0.2336 | benign | -0.677 | Destabilizing | 0.031 | N | 0.377 | neutral | None | None | None | None | N |
| P/H | 0.1401 | likely_benign | 0.1594 | benign | -0.146 | Destabilizing | 0.356 | N | 0.501 | neutral | None | None | None | None | N |
| P/I | 0.2475 | likely_benign | 0.2638 | benign | -0.217 | Destabilizing | 0.038 | N | 0.569 | neutral | None | None | None | None | N |
| P/K | 0.1252 | likely_benign | 0.2045 | benign | -0.405 | Destabilizing | None | N | 0.194 | neutral | None | None | None | None | N |
| P/L | 0.1093 | likely_benign | 0.1092 | benign | -0.217 | Destabilizing | 0.012 | N | 0.393 | neutral | N | 0.463903402 | None | None | N |
| P/M | 0.2138 | likely_benign | 0.2275 | benign | -0.37 | Destabilizing | 0.356 | N | 0.498 | neutral | None | None | None | None | N |
| P/N | 0.1894 | likely_benign | 0.2165 | benign | -0.192 | Destabilizing | 0.072 | N | 0.436 | neutral | None | None | None | None | N |
| P/Q | 0.107 | likely_benign | 0.1227 | benign | -0.374 | Destabilizing | 0.001 | N | 0.269 | neutral | N | 0.432553397 | None | None | N |
| P/R | 0.1285 | likely_benign | 0.173 | benign | 0.063 | Stabilizing | None | N | 0.301 | neutral | N | 0.449448562 | None | None | N |
| P/S | 0.101 | likely_benign | 0.1047 | benign | -0.642 | Destabilizing | 0.012 | N | 0.361 | neutral | N | 0.430398673 | None | None | N |
| P/T | 0.0641 | likely_benign | 0.0726 | benign | -0.615 | Destabilizing | None | N | 0.239 | neutral | N | 0.370953958 | None | None | N |
| P/V | 0.1668 | likely_benign | 0.1744 | benign | -0.28 | Destabilizing | 0.016 | N | 0.405 | neutral | None | None | None | None | N |
| P/W | 0.5738 | likely_pathogenic | 0.6026 | pathogenic | -0.661 | Destabilizing | 0.864 | D | 0.503 | neutral | None | None | None | None | N |
| P/Y | 0.3683 | ambiguous | 0.3995 | ambiguous | -0.364 | Destabilizing | 0.356 | N | 0.519 | 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.