Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 969 | 3130;3131;3132 | chr2:178783001;178783000;178782999 | chr2:179647728;179647727;179647726 |
| N2AB | 969 | 3130;3131;3132 | chr2:178783001;178783000;178782999 | chr2:179647728;179647727;179647726 |
| N2A | 969 | 3130;3131;3132 | chr2:178783001;178783000;178782999 | chr2:179647728;179647727;179647726 |
| N2B | 923 | 2992;2993;2994 | chr2:178783001;178783000;178782999 | chr2:179647728;179647727;179647726 |
| Novex-1 | 923 | 2992;2993;2994 | chr2:178783001;178783000;178782999 | chr2:179647728;179647727;179647726 |
| Novex-2 | 923 | 2992;2993;2994 | chr2:178783001;178783000;178782999 | chr2:179647728;179647727;179647726 |
| Novex-3 | 969 | 3130;3131;3132 | chr2:178783001;178783000;178782999 | chr2:179647728;179647727;179647726 |
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 | rs779994150  |
0.174 | 0.946 | N | 0.481 | 0.353 | 0.696690091256 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.83E-06 | 0 |
| Y/H | rs746986462 |
0.553 | None | N | 0.245 | 0.095 | 0.296329037015 | gnomAD-2.1.1 | 7.98E-06 | None | None | None | None | I | None | 0 | 2.89E-05 | None | 0 | 0 | None | 0 | None | 0 | 8.83E-06 | 0 |
| Y/H | rs746986462 |
0.553 | None | N | 0.245 | 0.095 | 0.296329037015 | gnomAD-4.0.0 | 3.18112E-06 | None | None | None | None | I | None | 0 | 2.28624E-05 | None | 0 | 0 | None | 0 | 0 | 2.8566E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.773 | likely_pathogenic | 0.6493 | pathogenic | -0.318 | Destabilizing | 0.104 | N | 0.531 | neutral | None | None | None | None | I |
| Y/C | 0.3912 | ambiguous | 0.2585 | benign | 0.043 | Stabilizing | 0.946 | D | 0.481 | neutral | N | 0.508860585 | None | None | I |
| Y/D | 0.668 | likely_pathogenic | 0.4702 | ambiguous | 0.778 | Stabilizing | 0.175 | N | 0.543 | neutral | N | 0.450207302 | None | None | I |
| Y/E | 0.819 | likely_pathogenic | 0.6849 | pathogenic | 0.744 | Stabilizing | 0.055 | N | 0.515 | neutral | None | None | None | None | I |
| Y/F | 0.1339 | likely_benign | 0.1181 | benign | -0.297 | Destabilizing | 0.001 | N | 0.307 | neutral | N | 0.474924225 | None | None | I |
| Y/G | 0.8577 | likely_pathogenic | 0.762 | pathogenic | -0.44 | Destabilizing | 0.22 | N | 0.55 | neutral | None | None | None | None | I |
| Y/H | 0.2213 | likely_benign | 0.1471 | benign | 0.307 | Stabilizing | None | N | 0.245 | neutral | N | 0.484814305 | None | None | I |
| Y/I | 0.5893 | likely_pathogenic | 0.4677 | ambiguous | -0.045 | Destabilizing | 0.22 | N | 0.499 | neutral | None | None | None | None | I |
| Y/K | 0.7611 | likely_pathogenic | 0.6029 | pathogenic | 0.234 | Stabilizing | 0.124 | N | 0.525 | neutral | None | None | None | None | I |
| Y/L | 0.656 | likely_pathogenic | 0.5434 | ambiguous | -0.045 | Destabilizing | 0.055 | N | 0.475 | neutral | None | None | None | None | I |
| Y/M | 0.7723 | likely_pathogenic | 0.6735 | pathogenic | -0.12 | Destabilizing | 0.859 | D | 0.483 | neutral | None | None | None | None | I |
| Y/N | 0.3438 | ambiguous | 0.2089 | benign | -0.013 | Destabilizing | 0.096 | N | 0.531 | neutral | N | 0.413096459 | None | None | I |
| Y/P | 0.9755 | likely_pathogenic | 0.9529 | pathogenic | -0.118 | Destabilizing | 0.667 | D | 0.5 | neutral | None | None | None | None | I |
| Y/Q | 0.6751 | likely_pathogenic | 0.4849 | ambiguous | 0.074 | Stabilizing | 0.011 | N | 0.317 | neutral | None | None | None | None | I |
| Y/R | 0.6064 | likely_pathogenic | 0.4357 | ambiguous | 0.339 | Stabilizing | 0.001 | N | 0.418 | neutral | None | None | None | None | I |
| Y/S | 0.3922 | ambiguous | 0.2645 | benign | -0.327 | Destabilizing | 0.175 | N | 0.551 | neutral | N | 0.421053661 | None | None | I |
| Y/T | 0.669 | likely_pathogenic | 0.5124 | ambiguous | -0.28 | Destabilizing | 0.364 | N | 0.542 | neutral | None | None | None | None | I |
| Y/V | 0.5381 | ambiguous | 0.4214 | ambiguous | -0.118 | Destabilizing | 0.22 | N | 0.509 | neutral | None | None | None | None | I |
| Y/W | 0.583 | likely_pathogenic | 0.5429 | ambiguous | -0.575 | Destabilizing | 0.859 | D | 0.45 | neutral | None | None | None | None | I |
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.