Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25148 | 75667;75668;75669 | chr2:178570690;178570689;178570688 | chr2:179435417;179435416;179435415 |
| N2AB | 23507 | 70744;70745;70746 | chr2:178570690;178570689;178570688 | chr2:179435417;179435416;179435415 |
| N2A | 22580 | 67963;67964;67965 | chr2:178570690;178570689;178570688 | chr2:179435417;179435416;179435415 |
| N2B | 16083 | 48472;48473;48474 | chr2:178570690;178570689;178570688 | chr2:179435417;179435416;179435415 |
| Novex-1 | 16208 | 48847;48848;48849 | chr2:178570690;178570689;178570688 | chr2:179435417;179435416;179435415 |
| Novex-2 | 16275 | 49048;49049;49050 | chr2:178570690;178570689;178570688 | chr2:179435417;179435416;179435415 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/C | None | None | 0.008 | N | 0.492 | 0.18 | 0.344945010812 | gnomAD-4.0.0 | 6.84303E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15937E-05 | 0 |
| G/D | rs1206394112  |
None | 0.001 | N | 0.3 | 0.12 | 0.0954503805726 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 1.31113E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| G/D | rs1206394112 |
None | 0.001 | N | 0.3 | 0.12 | 0.0954503805726 | gnomAD-4.0.0 | 2.4792E-06 | None | None | None | None | N | None | 0 | 5.00267E-05 | None | 0 | 0 | None | 0 | 0 | 8.47732E-07 | 0 | 0 |
| G/R | None | None | 0.003 | N | 0.365 | 0.13 | 0.277730125212 | gnomAD-4.0.0 | 7.52734E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.89536E-06 | 0 | 0 |
| G/S | rs778131439 |
-0.433 | 0.018 | N | 0.273 | 0.058 | 0.126345400529 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.88E-06 | 0 |
| G/S | rs778131439 |
-0.433 | 0.018 | N | 0.273 | 0.058 | 0.126345400529 | gnomAD-4.0.0 | 5.47443E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 3.47102E-04 | 5.39747E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/A | 0.1368 | likely_benign | 0.1626 | benign | -0.183 | Destabilizing | 0.001 | N | 0.199 | neutral | N | 0.472756794 | None | None | N |
| G/C | 0.1977 | likely_benign | 0.2437 | benign | -0.82 | Destabilizing | 0.008 | N | 0.492 | neutral | N | 0.488688301 | None | None | N |
| G/D | 0.1234 | likely_benign | 0.1345 | benign | -0.502 | Destabilizing | 0.001 | N | 0.3 | neutral | N | 0.377686188 | None | None | N |
| G/E | 0.1798 | likely_benign | 0.2024 | benign | -0.652 | Destabilizing | 0.002 | N | 0.242 | neutral | None | None | None | None | N |
| G/F | 0.6141 | likely_pathogenic | 0.7024 | pathogenic | -0.86 | Destabilizing | 0.818 | D | 0.517 | neutral | None | None | None | None | N |
| G/H | 0.3535 | ambiguous | 0.426 | ambiguous | -0.461 | Destabilizing | 0.818 | D | 0.48 | neutral | None | None | None | None | N |
| G/I | 0.4473 | ambiguous | 0.5265 | ambiguous | -0.28 | Destabilizing | 0.69 | D | 0.531 | neutral | None | None | None | None | N |
| G/K | 0.3561 | ambiguous | 0.4417 | ambiguous | -0.815 | Destabilizing | 0.241 | N | 0.484 | neutral | None | None | None | None | N |
| G/L | 0.4622 | ambiguous | 0.5495 | ambiguous | -0.28 | Destabilizing | 0.241 | N | 0.525 | neutral | None | None | None | None | N |
| G/M | 0.4747 | ambiguous | 0.5479 | ambiguous | -0.45 | Destabilizing | 0.981 | D | 0.495 | neutral | None | None | None | None | N |
| G/N | 0.155 | likely_benign | 0.1672 | benign | -0.432 | Destabilizing | 0.388 | N | 0.358 | neutral | None | None | None | None | N |
| G/P | 0.8907 | likely_pathogenic | 0.924 | pathogenic | -0.214 | Destabilizing | 0.818 | D | 0.508 | neutral | None | None | None | None | N |
| G/Q | 0.296 | likely_benign | 0.3443 | ambiguous | -0.684 | Destabilizing | 0.527 | D | 0.505 | neutral | None | None | None | None | N |
| G/R | 0.2866 | likely_benign | 0.3579 | ambiguous | -0.402 | Destabilizing | 0.003 | N | 0.365 | neutral | N | 0.458213783 | None | None | N |
| G/S | 0.1174 | likely_benign | 0.1231 | benign | -0.579 | Destabilizing | 0.018 | N | 0.273 | neutral | N | 0.486147379 | None | None | N |
| G/T | 0.2609 | likely_benign | 0.2992 | benign | -0.656 | Destabilizing | 0.241 | N | 0.485 | neutral | None | None | None | None | N |
| G/V | 0.2999 | likely_benign | 0.3673 | ambiguous | -0.214 | Destabilizing | 0.193 | N | 0.524 | neutral | N | 0.516817002 | None | None | N |
| G/W | 0.4315 | ambiguous | 0.5284 | ambiguous | -1.054 | Destabilizing | 0.981 | D | 0.523 | neutral | None | None | None | None | N |
| G/Y | 0.3667 | ambiguous | 0.455 | ambiguous | -0.688 | Destabilizing | 0.932 | D | 0.516 | 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.