Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35678 | 107257;107258;107259 | chr2:178528719;178528718;178528717 | chr2:179393446;179393445;179393444 |
| N2AB | 34037 | 102334;102335;102336 | chr2:178528719;178528718;178528717 | chr2:179393446;179393445;179393444 |
| N2A | 33110 | 99553;99554;99555 | chr2:178528719;178528718;178528717 | chr2:179393446;179393445;179393444 |
| N2B | 26613 | 80062;80063;80064 | chr2:178528719;178528718;178528717 | chr2:179393446;179393445;179393444 |
| Novex-1 | 26738 | 80437;80438;80439 | chr2:178528719;178528718;178528717 | chr2:179393446;179393445;179393444 |
| Novex-2 | 26805 | 80638;80639;80640 | chr2:178528719;178528718;178528717 | chr2:179393446;179393445;179393444 |
| 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/K | rs1558969484  |
None | 0.042 | N | 0.556 | 0.279 | 0.647793681525 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 6.48E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/K | rs1558969484 |
None | 0.042 | N | 0.556 | 0.279 | 0.647793681525 | gnomAD-4.0.0 | 2.73723E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.59807E-06 | 0 | 0 |
| I/M | None | None | 0.427 | N | 0.554 | 0.123 | 0.213573922156 | gnomAD-4.0.0 | 1.59179E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77377E-05 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | None | None | 0.081 | N | 0.52 | 0.25 | 0.524998368707 | gnomAD-4.0.0 | 6.84307E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99517E-07 | 0 | 0 |
| I/V | rs1404746485 |
-1.209 | None | N | 0.176 | 0.088 | 0.461759001683 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| I/V | rs1404746485 |
-1.209 | None | N | 0.176 | 0.088 | 0.461759001683 | gnomAD-4.0.0 | 1.59176E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85878E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.5964 | likely_pathogenic | 0.6046 | pathogenic | -2.118 | Highly Destabilizing | 0.025 | N | 0.444 | neutral | None | None | None | None | N |
| I/C | 0.8978 | likely_pathogenic | 0.8901 | pathogenic | -1.372 | Destabilizing | 0.883 | D | 0.538 | neutral | None | None | None | None | N |
| I/D | 0.8551 | likely_pathogenic | 0.8774 | pathogenic | -1.738 | Destabilizing | 0.055 | N | 0.562 | neutral | None | None | None | None | N |
| I/E | 0.6411 | likely_pathogenic | 0.6629 | pathogenic | -1.664 | Destabilizing | None | N | 0.488 | neutral | None | None | None | None | N |
| I/F | 0.2206 | likely_benign | 0.1967 | benign | -1.394 | Destabilizing | 0.497 | N | 0.554 | neutral | None | None | None | None | N |
| I/G | 0.8859 | likely_pathogenic | 0.8928 | pathogenic | -2.521 | Highly Destabilizing | 0.22 | N | 0.563 | neutral | None | None | None | None | N |
| I/H | 0.6378 | likely_pathogenic | 0.6586 | pathogenic | -1.76 | Destabilizing | 0.667 | D | 0.595 | neutral | None | None | None | None | N |
| I/K | 0.5552 | ambiguous | 0.5781 | pathogenic | -1.496 | Destabilizing | 0.042 | N | 0.556 | neutral | N | 0.457692207 | None | None | N |
| I/L | 0.1961 | likely_benign | 0.1777 | benign | -1.033 | Destabilizing | 0.019 | N | 0.351 | neutral | N | 0.460119224 | None | None | N |
| I/M | 0.1783 | likely_benign | 0.1631 | benign | -0.824 | Destabilizing | 0.427 | N | 0.554 | neutral | N | 0.460812657 | None | None | N |
| I/N | 0.4356 | ambiguous | 0.4785 | ambiguous | -1.425 | Destabilizing | 0.22 | N | 0.587 | neutral | None | None | None | None | N |
| I/P | 0.9769 | likely_pathogenic | 0.9817 | pathogenic | -1.367 | Destabilizing | 0.364 | N | 0.597 | neutral | None | None | None | None | N |
| I/Q | 0.5713 | likely_pathogenic | 0.594 | pathogenic | -1.529 | Destabilizing | 0.124 | N | 0.579 | neutral | None | None | None | None | N |
| I/R | 0.4429 | ambiguous | 0.4756 | ambiguous | -0.961 | Destabilizing | 0.175 | N | 0.595 | neutral | N | 0.458905715 | None | None | N |
| I/S | 0.4654 | ambiguous | 0.4914 | ambiguous | -2.125 | Highly Destabilizing | 0.055 | N | 0.543 | neutral | None | None | None | None | N |
| I/T | 0.3311 | likely_benign | 0.3325 | benign | -1.929 | Destabilizing | 0.081 | N | 0.52 | neutral | N | 0.458558999 | None | None | N |
| I/V | 0.1205 | likely_benign | 0.107 | benign | -1.367 | Destabilizing | None | N | 0.176 | neutral | N | 0.439973238 | None | None | N |
| I/W | 0.8519 | likely_pathogenic | 0.8414 | pathogenic | -1.557 | Destabilizing | 0.958 | D | 0.609 | neutral | None | None | None | None | N |
| I/Y | 0.6011 | likely_pathogenic | 0.5933 | pathogenic | -1.329 | Destabilizing | 0.667 | D | 0.545 | 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.