Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2279 | 7060;7061;7062 | chr2:178774429;178774428;178774427 | chr2:179639156;179639155;179639154 |
| N2AB | 2279 | 7060;7061;7062 | chr2:178774429;178774428;178774427 | chr2:179639156;179639155;179639154 |
| N2A | 2279 | 7060;7061;7062 | chr2:178774429;178774428;178774427 | chr2:179639156;179639155;179639154 |
| N2B | 2233 | 6922;6923;6924 | chr2:178774429;178774428;178774427 | chr2:179639156;179639155;179639154 |
| Novex-1 | 2233 | 6922;6923;6924 | chr2:178774429;178774428;178774427 | chr2:179639156;179639155;179639154 |
| Novex-2 | 2233 | 6922;6923;6924 | chr2:178774429;178774428;178774427 | chr2:179639156;179639155;179639154 |
| Novex-3 | 2279 | 7060;7061;7062 | chr2:178774429;178774428;178774427 | chr2:179639156;179639155;179639154 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | rs143679901  |
-1.32 | 0.865 | N | 0.551 | 0.356 | None | gnomAD-2.1.1 | 7.98E-06 | None | None | None | None | N | None | 1.23198E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| P/A | rs143679901 |
-1.32 | 0.865 | N | 0.551 | 0.356 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 7.24E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/A | rs143679901 |
-1.32 | 0.865 | N | 0.551 | 0.356 | None | 1000 genomes | 5.99042E-04 | None | None | None | None | N | None | 2.3E-03 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| P/A | rs143679901 |
-1.32 | 0.865 | N | 0.551 | 0.356 | None | gnomAD-4.0.0 | 4.33832E-06 | None | None | None | None | N | None | 6.66649E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.20041E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.2773 | likely_benign | 0.2523 | benign | -1.602 | Destabilizing | 0.865 | D | 0.551 | neutral | N | 0.484220559 | None | None | N |
| P/C | 0.933 | likely_pathogenic | 0.9268 | pathogenic | -0.977 | Destabilizing | 0.999 | D | 0.714 | prob.delet. | None | None | None | None | N |
| P/D | 0.9348 | likely_pathogenic | 0.9222 | pathogenic | -1.296 | Destabilizing | 0.983 | D | 0.637 | neutral | None | None | None | None | N |
| P/E | 0.8238 | likely_pathogenic | 0.7934 | pathogenic | -1.273 | Destabilizing | 0.983 | D | 0.631 | neutral | None | None | None | None | N |
| P/F | 0.9114 | likely_pathogenic | 0.9056 | pathogenic | -1.189 | Destabilizing | 0.998 | D | 0.727 | prob.delet. | None | None | None | None | N |
| P/G | 0.8265 | likely_pathogenic | 0.8053 | pathogenic | -1.948 | Destabilizing | 0.895 | D | 0.639 | neutral | None | None | None | None | N |
| P/H | 0.8003 | likely_pathogenic | 0.7835 | pathogenic | -1.461 | Destabilizing | 0.998 | D | 0.705 | prob.neutral | None | None | None | None | N |
| P/I | 0.7756 | likely_pathogenic | 0.7591 | pathogenic | -0.739 | Destabilizing | 0.992 | D | 0.717 | prob.delet. | None | None | None | None | N |
| P/K | 0.9111 | likely_pathogenic | 0.8913 | pathogenic | -1.222 | Destabilizing | 0.968 | D | 0.629 | neutral | None | None | None | None | N |
| P/L | 0.3924 | ambiguous | 0.3576 | ambiguous | -0.739 | Destabilizing | 0.978 | D | 0.688 | prob.neutral | N | 0.46021256 | None | None | N |
| P/M | 0.7306 | likely_pathogenic | 0.7075 | pathogenic | -0.535 | Destabilizing | 0.999 | D | 0.709 | prob.delet. | None | None | None | None | N |
| P/N | 0.8828 | likely_pathogenic | 0.8676 | pathogenic | -1.019 | Destabilizing | 0.968 | D | 0.676 | prob.neutral | None | None | None | None | N |
| P/Q | 0.7067 | likely_pathogenic | 0.6629 | pathogenic | -1.164 | Destabilizing | 0.978 | D | 0.675 | prob.neutral | N | 0.496178241 | None | None | N |
| P/R | 0.8155 | likely_pathogenic | 0.7847 | pathogenic | -0.736 | Destabilizing | 0.978 | D | 0.71 | prob.delet. | N | 0.484220559 | None | None | N |
| P/S | 0.5395 | ambiguous | 0.4979 | ambiguous | -1.599 | Destabilizing | 0.284 | N | 0.398 | neutral | N | 0.471925708 | None | None | N |
| P/T | 0.4683 | ambiguous | 0.4299 | ambiguous | -1.463 | Destabilizing | 0.957 | D | 0.624 | neutral | N | 0.436893351 | None | None | N |
| P/V | 0.6161 | likely_pathogenic | 0.5972 | pathogenic | -0.992 | Destabilizing | 0.983 | D | 0.682 | prob.neutral | None | None | None | None | N |
| P/W | 0.9638 | likely_pathogenic | 0.9599 | pathogenic | -1.398 | Destabilizing | 0.999 | D | 0.718 | prob.delet. | None | None | None | None | N |
| P/Y | 0.9148 | likely_pathogenic | 0.9103 | pathogenic | -1.103 | Destabilizing | 0.999 | D | 0.727 | prob.delet. | 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.