Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 6926 | 21001;21002;21003 | chr2:178725428;178725427;178725426 | chr2:179590155;179590154;179590153 |
| N2AB | 6609 | 20050;20051;20052 | chr2:178725428;178725427;178725426 | chr2:179590155;179590154;179590153 |
| N2A | 5682 | 17269;17270;17271 | chr2:178725428;178725427;178725426 | chr2:179590155;179590154;179590153 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs1430184680  |
-2.656 | 0.003 | N | 0.419 | 0.147 | 0.32082282376 | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.31E-05 | None | 0 | 0 | 0 |
| I/T | rs1430184680 |
-2.656 | 0.003 | N | 0.419 | 0.147 | 0.32082282376 | gnomAD-4.0.0 | 2.74155E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 4.66027E-05 | 0 |
| I/V | rs752400157 |
-1.605 | 0.001 | N | 0.257 | 0.032 | 0.406668915854 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.61E-05 | None | 0 | None | 0 | 0 | 0 |
| I/V | rs752400157 |
-1.605 | 0.001 | N | 0.257 | 0.032 | 0.406668915854 | gnomAD-4.0.0 | 1.59728E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.78025E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.3396 | likely_benign | 0.2836 | benign | -2.644 | Highly Destabilizing | 0.054 | N | 0.533 | neutral | None | None | None | None | N |
| I/C | 0.6672 | likely_pathogenic | 0.6138 | pathogenic | -1.804 | Destabilizing | 0.818 | D | 0.631 | neutral | None | None | None | None | N |
| I/D | 0.8346 | likely_pathogenic | 0.7881 | pathogenic | -2.999 | Highly Destabilizing | 0.388 | N | 0.649 | neutral | None | None | None | None | N |
| I/E | 0.7037 | likely_pathogenic | 0.6528 | pathogenic | -2.825 | Highly Destabilizing | 0.388 | N | 0.628 | neutral | None | None | None | None | N |
| I/F | 0.1507 | likely_benign | 0.1393 | benign | -1.538 | Destabilizing | 0.627 | D | 0.631 | neutral | N | 0.473986158 | None | None | N |
| I/G | 0.6774 | likely_pathogenic | 0.6091 | pathogenic | -3.126 | Highly Destabilizing | 0.388 | N | 0.65 | neutral | None | None | None | None | N |
| I/H | 0.4422 | ambiguous | 0.3963 | ambiguous | -2.455 | Highly Destabilizing | 0.981 | D | 0.673 | neutral | None | None | None | None | N |
| I/K | 0.3736 | ambiguous | 0.3339 | benign | -1.937 | Destabilizing | 0.388 | N | 0.631 | neutral | None | None | None | None | N |
| I/L | 0.1343 | likely_benign | 0.1245 | benign | -1.257 | Destabilizing | 0.041 | N | 0.437 | neutral | N | 0.46736683 | None | None | N |
| I/M | 0.1326 | likely_benign | 0.1258 | benign | -1.154 | Destabilizing | 0.627 | D | 0.638 | neutral | N | 0.473986158 | None | None | N |
| I/N | 0.3117 | likely_benign | 0.2857 | benign | -2.15 | Highly Destabilizing | 0.324 | N | 0.66 | neutral | N | 0.511773755 | None | None | N |
| I/P | 0.9643 | likely_pathogenic | 0.9524 | pathogenic | -1.701 | Destabilizing | 0.818 | D | 0.647 | neutral | None | None | None | None | N |
| I/Q | 0.4623 | ambiguous | 0.4117 | ambiguous | -2.108 | Highly Destabilizing | 0.818 | D | 0.65 | neutral | None | None | None | None | N |
| I/R | 0.2614 | likely_benign | 0.2311 | benign | -1.509 | Destabilizing | 0.818 | D | 0.632 | neutral | None | None | None | None | N |
| I/S | 0.2523 | likely_benign | 0.221 | benign | -2.796 | Highly Destabilizing | 0.018 | N | 0.527 | neutral | N | 0.432195464 | None | None | N |
| I/T | 0.1496 | likely_benign | 0.1299 | benign | -2.501 | Highly Destabilizing | 0.003 | N | 0.419 | neutral | N | 0.321870191 | None | None | N |
| I/V | 0.0746 | likely_benign | 0.0698 | benign | -1.701 | Destabilizing | 0.001 | N | 0.257 | neutral | N | 0.416284649 | None | None | N |
| I/W | 0.7417 | likely_pathogenic | 0.6972 | pathogenic | -1.906 | Destabilizing | 0.981 | D | 0.688 | prob.neutral | None | None | None | None | N |
| I/Y | 0.453 | ambiguous | 0.4193 | ambiguous | -1.693 | Destabilizing | 0.818 | D | 0.635 | 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.