Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32395 | 97408;97409;97410 | chr2:178542671;178542670;178542669 | chr2:179407398;179407397;179407396 |
| N2AB | 30754 | 92485;92486;92487 | chr2:178542671;178542670;178542669 | chr2:179407398;179407397;179407396 |
| N2A | 29827 | 89704;89705;89706 | chr2:178542671;178542670;178542669 | chr2:179407398;179407397;179407396 |
| N2B | 23330 | 70213;70214;70215 | chr2:178542671;178542670;178542669 | chr2:179407398;179407397;179407396 |
| Novex-1 | 23455 | 70588;70589;70590 | chr2:178542671;178542670;178542669 | chr2:179407398;179407397;179407396 |
| Novex-2 | 23522 | 70789;70790;70791 | chr2:178542671;178542670;178542669 | chr2:179407398;179407397;179407396 |
| 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/F | None | None | 0.942 | N | 0.553 | 0.307 | 0.663397737457 | gnomAD-4.0.0 | 6.855E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.01374E-07 | 0 | 0 |
| I/T | None | None | 0.822 | N | 0.571 | 0.311 | 0.743037970187 | gnomAD-4.0.0 | 2.7418E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.7039E-06 | 0 | 1.6597E-05 |
| I/V | None | None | 0.006 | N | 0.207 | 0.051 | 0.524271286562 | gnomAD-4.0.0 | 6.855E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.01374E-07 | 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 | 0.6659 | likely_pathogenic | 0.6285 | pathogenic | -2.015 | Highly Destabilizing | 0.754 | D | 0.533 | neutral | None | None | None | None | N |
| I/C | 0.7851 | likely_pathogenic | 0.7775 | pathogenic | -1.083 | Destabilizing | 0.998 | D | 0.633 | neutral | None | None | None | None | N |
| I/D | 0.9022 | likely_pathogenic | 0.8897 | pathogenic | -1.973 | Destabilizing | 0.993 | D | 0.755 | deleterious | None | None | None | None | N |
| I/E | 0.8171 | likely_pathogenic | 0.7959 | pathogenic | -1.902 | Destabilizing | 0.978 | D | 0.754 | deleterious | None | None | None | None | N |
| I/F | 0.3226 | likely_benign | 0.2948 | benign | -1.338 | Destabilizing | 0.942 | D | 0.553 | neutral | N | 0.513702992 | None | None | N |
| I/G | 0.8916 | likely_pathogenic | 0.8642 | pathogenic | -2.405 | Highly Destabilizing | 0.978 | D | 0.735 | prob.delet. | None | None | None | None | N |
| I/H | 0.668 | likely_pathogenic | 0.6503 | pathogenic | -1.749 | Destabilizing | 0.998 | D | 0.765 | deleterious | None | None | None | None | N |
| I/K | 0.6392 | likely_pathogenic | 0.6429 | pathogenic | -1.56 | Destabilizing | 0.978 | D | 0.753 | deleterious | None | None | None | None | N |
| I/L | 0.1808 | likely_benign | 0.1722 | benign | -0.968 | Destabilizing | 0.294 | N | 0.398 | neutral | N | 0.509142534 | None | None | N |
| I/M | 0.1626 | likely_benign | 0.1465 | benign | -0.659 | Destabilizing | 0.942 | D | 0.564 | neutral | N | 0.498392215 | None | None | N |
| I/N | 0.4207 | ambiguous | 0.4025 | ambiguous | -1.503 | Destabilizing | 0.99 | D | 0.769 | deleterious | N | 0.49425044 | None | None | N |
| I/P | 0.9911 | likely_pathogenic | 0.9874 | pathogenic | -1.29 | Destabilizing | 0.993 | D | 0.767 | deleterious | None | None | None | None | N |
| I/Q | 0.6296 | likely_pathogenic | 0.6145 | pathogenic | -1.61 | Destabilizing | 0.993 | D | 0.765 | deleterious | None | None | None | None | N |
| I/R | 0.5538 | ambiguous | 0.5416 | ambiguous | -0.975 | Destabilizing | 0.978 | D | 0.768 | deleterious | None | None | None | None | N |
| I/S | 0.5633 | ambiguous | 0.5355 | ambiguous | -2.08 | Highly Destabilizing | 0.942 | D | 0.657 | neutral | D | 0.522917121 | None | None | N |
| I/T | 0.3689 | ambiguous | 0.368 | ambiguous | -1.9 | Destabilizing | 0.822 | D | 0.571 | neutral | N | 0.477259403 | None | None | N |
| I/V | 0.0857 | likely_benign | 0.0879 | benign | -1.29 | Destabilizing | 0.006 | N | 0.207 | neutral | N | 0.499445616 | None | None | N |
| I/W | 0.9104 | likely_pathogenic | 0.8932 | pathogenic | -1.592 | Destabilizing | 0.998 | D | 0.743 | deleterious | None | None | None | None | N |
| I/Y | 0.6937 | likely_pathogenic | 0.678 | pathogenic | -1.334 | Destabilizing | 0.978 | 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.