Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21969 | 66130;66131;66132 | chr2:178582551;178582550;178582549 | chr2:179447278;179447277;179447276 |
| N2AB | 20328 | 61207;61208;61209 | chr2:178582551;178582550;178582549 | chr2:179447278;179447277;179447276 |
| N2A | 19401 | 58426;58427;58428 | chr2:178582551;178582550;178582549 | chr2:179447278;179447277;179447276 |
| N2B | 12904 | 38935;38936;38937 | chr2:178582551;178582550;178582549 | chr2:179447278;179447277;179447276 |
| Novex-1 | 13029 | 39310;39311;39312 | chr2:178582551;178582550;178582549 | chr2:179447278;179447277;179447276 |
| Novex-2 | 13096 | 39511;39512;39513 | chr2:178582551;178582550;178582549 | chr2:179447278;179447277;179447276 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/C | rs777698555  |
0.118 | 0.015 | N | 0.265 | 0.201 | None | gnomAD-2.1.1 | 8.49E-05 | None | None | None | None | N | None | 0 | 2.91E-05 | None | 0 | 0 | None | 0 | None | 4.67E-05 | 1.69974E-04 | 0 |
| Y/C | rs777698555 |
0.118 | 0.015 | N | 0.265 | 0.201 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 9.41E-05 | 0 | 2.94E-05 | 0 | 0 |
| Y/C | rs777698555 |
0.118 | 0.015 | N | 0.265 | 0.201 | None | gnomAD-4.0.0 | 4.21819E-05 | None | None | None | None | N | None | 0 | 1.66973E-05 | None | 0 | 0 | None | 4.68911E-05 | 0 | 4.66566E-05 | 0 | 1.44268E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.7268 | likely_pathogenic | 0.588 | pathogenic | -2.484 | Highly Destabilizing | 0.59 | D | 0.349 | neutral | None | None | None | None | N |
| Y/C | 0.3108 | likely_benign | 0.2023 | benign | -0.926 | Destabilizing | 0.015 | N | 0.265 | neutral | N | 0.507109802 | None | None | N |
| Y/D | 0.5975 | likely_pathogenic | 0.4636 | ambiguous | -1.777 | Destabilizing | 0.979 | D | 0.414 | neutral | N | 0.406772236 | None | None | N |
| Y/E | 0.8577 | likely_pathogenic | 0.7943 | pathogenic | -1.727 | Destabilizing | 0.984 | D | 0.413 | neutral | None | None | None | None | N |
| Y/F | 0.0796 | likely_benign | 0.0791 | benign | -1.288 | Destabilizing | 0.003 | N | 0.079 | neutral | N | 0.39515252 | None | None | N |
| Y/G | 0.6433 | likely_pathogenic | 0.4547 | ambiguous | -2.798 | Highly Destabilizing | 0.854 | D | 0.405 | neutral | None | None | None | None | N |
| Y/H | 0.2843 | likely_benign | 0.2245 | benign | -1.441 | Destabilizing | 0.979 | D | 0.429 | neutral | N | 0.432150683 | None | None | N |
| Y/I | 0.6984 | likely_pathogenic | 0.6021 | pathogenic | -1.522 | Destabilizing | 0.742 | D | 0.371 | neutral | None | None | None | None | N |
| Y/K | 0.8548 | likely_pathogenic | 0.7848 | pathogenic | -1.228 | Destabilizing | 0.953 | D | 0.407 | neutral | None | None | None | None | N |
| Y/L | 0.525 | ambiguous | 0.4367 | ambiguous | -1.522 | Destabilizing | 0.373 | N | 0.333 | neutral | None | None | None | None | N |
| Y/M | 0.6839 | likely_pathogenic | 0.5772 | pathogenic | -0.988 | Destabilizing | 0.984 | D | 0.383 | neutral | None | None | None | None | N |
| Y/N | 0.3082 | likely_benign | 0.2093 | benign | -1.425 | Destabilizing | 0.979 | D | 0.411 | neutral | N | 0.411945983 | None | None | N |
| Y/P | 0.9766 | likely_pathogenic | 0.9537 | pathogenic | -1.839 | Destabilizing | 0.984 | D | 0.405 | neutral | None | None | None | None | N |
| Y/Q | 0.7544 | likely_pathogenic | 0.6334 | pathogenic | -1.466 | Destabilizing | 0.984 | D | 0.379 | neutral | None | None | None | None | N |
| Y/R | 0.7434 | likely_pathogenic | 0.6424 | pathogenic | -0.675 | Destabilizing | 0.984 | D | 0.408 | neutral | None | None | None | None | N |
| Y/S | 0.3897 | ambiguous | 0.2513 | benign | -1.843 | Destabilizing | 0.684 | D | 0.367 | neutral | N | 0.33656279 | None | None | N |
| Y/T | 0.5661 | likely_pathogenic | 0.3944 | ambiguous | -1.695 | Destabilizing | 0.742 | D | 0.381 | neutral | None | None | None | None | N |
| Y/V | 0.5748 | likely_pathogenic | 0.4746 | ambiguous | -1.839 | Destabilizing | 0.742 | D | 0.339 | neutral | None | None | None | None | N |
| Y/W | 0.5357 | ambiguous | 0.4774 | ambiguous | -1.007 | Destabilizing | 0.984 | D | 0.415 | 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.