Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26836 | 80731;80732;80733 | chr2:178565626;178565625;178565624 | chr2:179430353;179430352;179430351 |
| N2AB | 25195 | 75808;75809;75810 | chr2:178565626;178565625;178565624 | chr2:179430353;179430352;179430351 |
| N2A | 24268 | 73027;73028;73029 | chr2:178565626;178565625;178565624 | chr2:179430353;179430352;179430351 |
| N2B | 17771 | 53536;53537;53538 | chr2:178565626;178565625;178565624 | chr2:179430353;179430352;179430351 |
| Novex-1 | 17896 | 53911;53912;53913 | chr2:178565626;178565625;178565624 | chr2:179430353;179430352;179430351 |
| Novex-2 | 17963 | 54112;54113;54114 | chr2:178565626;178565625;178565624 | chr2:179430353;179430352;179430351 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/S | None | None | 0.961 | N | 0.469 | 0.412 | 0.552822141497 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 6.33473E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| C/Y | rs893506951  |
None | 0.999 | N | 0.694 | 0.368 | 0.661710244528 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| C/Y | rs893506951 |
None | 0.999 | N | 0.694 | 0.368 | 0.661710244528 | gnomAD-4.0.0 | 6.57575E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47098E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/A | 0.4534 | ambiguous | 0.4923 | ambiguous | -2.114 | Highly Destabilizing | 0.964 | D | 0.437 | neutral | None | None | None | None | N |
| C/D | 0.8342 | likely_pathogenic | 0.8647 | pathogenic | -1.003 | Destabilizing | 0.998 | D | 0.7 | prob.neutral | None | None | None | None | N |
| C/E | 0.8598 | likely_pathogenic | 0.8905 | pathogenic | -0.851 | Destabilizing | 0.998 | D | 0.712 | prob.delet. | None | None | None | None | N |
| C/F | 0.3783 | ambiguous | 0.4245 | ambiguous | -1.338 | Destabilizing | 0.999 | D | 0.675 | neutral | N | 0.501567909 | None | None | N |
| C/G | 0.1785 | likely_benign | 0.1994 | benign | -2.444 | Highly Destabilizing | 0.997 | D | 0.641 | neutral | N | 0.513342341 | None | None | N |
| C/H | 0.6863 | likely_pathogenic | 0.742 | pathogenic | -2.265 | Highly Destabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | N |
| C/I | 0.6943 | likely_pathogenic | 0.7371 | pathogenic | -1.231 | Destabilizing | 0.996 | D | 0.566 | neutral | None | None | None | None | N |
| C/K | 0.8206 | likely_pathogenic | 0.8578 | pathogenic | -1.484 | Destabilizing | 0.998 | D | 0.701 | prob.neutral | None | None | None | None | N |
| C/L | 0.3498 | ambiguous | 0.3696 | ambiguous | -1.231 | Destabilizing | 0.985 | D | 0.454 | neutral | None | None | None | None | N |
| C/M | 0.5824 | likely_pathogenic | 0.6448 | pathogenic | 0.101 | Stabilizing | 1.0 | D | 0.636 | neutral | None | None | None | None | N |
| C/N | 0.4759 | ambiguous | 0.5292 | ambiguous | -1.675 | Destabilizing | 0.998 | D | 0.714 | prob.delet. | None | None | None | None | N |
| C/P | 0.5093 | ambiguous | 0.6223 | pathogenic | -1.503 | Destabilizing | 0.999 | D | 0.736 | prob.delet. | None | None | None | None | N |
| C/Q | 0.6295 | likely_pathogenic | 0.6926 | pathogenic | -1.456 | Destabilizing | 0.999 | D | 0.755 | deleterious | None | None | None | None | N |
| C/R | 0.5133 | ambiguous | 0.5682 | pathogenic | -1.343 | Destabilizing | 0.997 | D | 0.739 | prob.delet. | N | 0.473418516 | None | None | N |
| C/S | 0.3568 | ambiguous | 0.3935 | ambiguous | -2.188 | Highly Destabilizing | 0.961 | D | 0.469 | neutral | N | 0.453331245 | None | None | N |
| C/T | 0.4145 | ambiguous | 0.434 | ambiguous | -1.859 | Destabilizing | 0.469 | N | 0.391 | neutral | None | None | None | None | N |
| C/V | 0.5624 | ambiguous | 0.6096 | pathogenic | -1.503 | Destabilizing | 0.985 | D | 0.469 | neutral | None | None | None | None | N |
| C/W | 0.695 | likely_pathogenic | 0.7517 | pathogenic | -1.404 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | N | 0.490434091 | None | None | N |
| C/Y | 0.4616 | ambiguous | 0.5294 | ambiguous | -1.421 | Destabilizing | 0.999 | D | 0.694 | prob.neutral | N | 0.472076347 | 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.