Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 9563 | 28912;28913;28914 | chr2:178709632;178709631;178709630 | chr2:179574359;179574358;179574357 |
| N2AB | 9246 | 27961;27962;27963 | chr2:178709632;178709631;178709630 | chr2:179574359;179574358;179574357 |
| N2A | 8319 | 25180;25181;25182 | chr2:178709632;178709631;178709630 | chr2:179574359;179574358;179574357 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/S | None | None | 0.852 | None | 0.535 | 0.168 | 0.767653027609 | gnomAD-4.0.0 | 6.84185E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.51927E-05 | None | 0 | 0 | 0 | 0 | 0 |
| L/W | rs770692880  |
-0.894 | 0.999 | None | 0.619 | 0.383 | 0.832404605066 | gnomAD-2.1.1 | 3.21E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 4.60971E-04 | None | 0 | None | 0 | 0 | 0 |
| L/W | rs770692880 |
-0.894 | 0.999 | None | 0.619 | 0.383 | 0.832404605066 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 3.84468E-04 | None | 0 | 0 | 0 | 0 | 0 |
| L/W | rs770692880 |
-0.894 | 0.999 | None | 0.619 | 0.383 | 0.832404605066 | gnomAD-4.0.0 | 3.71786E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 1.33642E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.6352 | likely_pathogenic | 0.6797 | pathogenic | -1.459 | Destabilizing | 0.863 | D | 0.462 | neutral | None | None | None | None | I |
| L/C | 0.8236 | likely_pathogenic | 0.841 | pathogenic | -1.096 | Destabilizing | 0.999 | D | 0.563 | neutral | None | None | None | None | I |
| L/D | 0.8928 | likely_pathogenic | 0.9107 | pathogenic | -0.571 | Destabilizing | 0.991 | D | 0.619 | neutral | None | None | None | None | I |
| L/E | 0.7286 | likely_pathogenic | 0.754 | pathogenic | -0.586 | Destabilizing | 0.939 | D | 0.583 | neutral | None | None | None | None | I |
| L/F | 0.3006 | likely_benign | 0.3298 | benign | -1.285 | Destabilizing | 0.988 | D | 0.554 | neutral | None | None | None | None | I |
| L/G | 0.8602 | likely_pathogenic | 0.8841 | pathogenic | -1.735 | Destabilizing | 0.969 | D | 0.579 | neutral | None | None | None | None | I |
| L/H | 0.5288 | ambiguous | 0.5698 | pathogenic | -1.04 | Destabilizing | 0.999 | D | 0.6 | neutral | None | None | None | None | I |
| L/I | 0.1483 | likely_benign | 0.1542 | benign | -0.792 | Destabilizing | 0.884 | D | 0.455 | neutral | None | None | None | None | I |
| L/K | 0.6055 | likely_pathogenic | 0.639 | pathogenic | -0.684 | Destabilizing | 0.884 | D | 0.541 | neutral | None | None | None | None | I |
| L/M | 0.2159 | likely_benign | 0.2331 | benign | -0.646 | Destabilizing | 0.988 | D | 0.573 | neutral | None | None | None | None | I |
| L/N | 0.6438 | likely_pathogenic | 0.6813 | pathogenic | -0.477 | Destabilizing | 0.991 | D | 0.61 | neutral | None | None | None | None | I |
| L/P | 0.8257 | likely_pathogenic | 0.8915 | pathogenic | -0.984 | Destabilizing | 0.997 | D | 0.623 | neutral | None | None | None | None | I |
| L/Q | 0.4135 | ambiguous | 0.4624 | ambiguous | -0.692 | Destabilizing | 0.982 | D | 0.621 | neutral | None | None | None | None | I |
| L/R | 0.4645 | ambiguous | 0.4923 | ambiguous | -0.212 | Destabilizing | 0.046 | N | 0.39 | neutral | None | None | None | None | I |
| L/S | 0.6551 | likely_pathogenic | 0.7149 | pathogenic | -1.173 | Destabilizing | 0.852 | D | 0.535 | neutral | None | None | None | None | I |
| L/T | 0.5068 | ambiguous | 0.5709 | pathogenic | -1.07 | Destabilizing | 0.079 | N | 0.289 | neutral | None | None | None | None | I |
| L/V | 0.1892 | likely_benign | 0.1985 | benign | -0.984 | Destabilizing | 0.134 | N | 0.245 | neutral | None | None | None | None | I |
| L/W | 0.565 | likely_pathogenic | 0.5681 | pathogenic | -1.285 | Destabilizing | 0.999 | D | 0.619 | neutral | None | None | None | None | I |
| L/Y | 0.6135 | likely_pathogenic | 0.6347 | pathogenic | -1.009 | Destabilizing | 0.997 | D | 0.596 | 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.