Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 6779 | 20560;20561;20562 | chr2:178725987;178725986;178725985 | chr2:179590714;179590713;179590712 |
| N2AB | 6462 | 19609;19610;19611 | chr2:178725987;178725986;178725985 | chr2:179590714;179590713;179590712 |
| N2A | 5535 | 16828;16829;16830 | chr2:178725987;178725986;178725985 | chr2:179590714;179590713;179590712 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/C | rs149470241  |
-0.163 | 0.99 | N | 0.539 | 0.501 | None | gnomAD-2.1.1 | 5.7142E-04 | None | None | None | None | N | None | 3.36814E-04 | 1.19603E-04 | None | 0 | 0 | None | 0 | None | 0 | 1.12904E-03 | 2.91545E-04 |
| S/C | rs149470241 |
-0.163 | 0.99 | N | 0.539 | 0.501 | None | gnomAD-3.1.2 | 5.9811E-04 | None | None | None | None | N | None | 3.61847E-04 | 1.96721E-04 | 0 | 0 | 0 | None | 0 | 0 | 1.07331E-03 | 0 | 0 |
| S/C | rs149470241 |
-0.163 | 0.99 | N | 0.539 | 0.501 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| S/C | rs149470241 |
-0.163 | 0.99 | N | 0.539 | 0.501 | None | gnomAD-4.0.0 | 1.53006E-03 | None | None | None | None | N | None | 3.21569E-04 | 1.01564E-04 | None | 0 | 0 | None | 4.70072E-05 | 0 | 2.01995E-03 | 1.12065E-05 | 7.73171E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0956 | likely_benign | 0.1033 | benign | -0.518 | Destabilizing | 0.25 | N | 0.537 | neutral | None | None | None | None | N |
| S/C | 0.1201 | likely_benign | 0.1435 | benign | -0.427 | Destabilizing | 0.99 | D | 0.539 | neutral | N | 0.503622908 | None | None | N |
| S/D | 0.4337 | ambiguous | 0.4473 | ambiguous | -0.198 | Destabilizing | 0.005 | N | 0.434 | neutral | None | None | None | None | N |
| S/E | 0.5326 | ambiguous | 0.5822 | pathogenic | -0.16 | Destabilizing | 0.447 | N | 0.521 | neutral | None | None | None | None | N |
| S/F | 0.1589 | likely_benign | 0.184 | benign | -0.608 | Destabilizing | 0.85 | D | 0.593 | neutral | None | None | None | None | N |
| S/G | 0.1278 | likely_benign | 0.1351 | benign | -0.81 | Destabilizing | 0.549 | D | 0.528 | neutral | N | 0.4980895 | None | None | N |
| S/H | 0.2636 | likely_benign | 0.3004 | benign | -1.241 | Destabilizing | 0.005 | N | 0.41 | neutral | None | None | None | None | N |
| S/I | 0.0898 | likely_benign | 0.115 | benign | 0.153 | Stabilizing | 0.379 | N | 0.549 | neutral | N | 0.47335788 | None | None | N |
| S/K | 0.5901 | likely_pathogenic | 0.6703 | pathogenic | -0.622 | Destabilizing | 0.617 | D | 0.485 | neutral | None | None | None | None | N |
| S/L | 0.0906 | likely_benign | 0.1066 | benign | 0.153 | Stabilizing | 0.005 | N | 0.515 | neutral | None | None | None | None | N |
| S/M | 0.16 | likely_benign | 0.1777 | benign | 0.2 | Stabilizing | 0.25 | N | 0.469 | neutral | None | None | None | None | N |
| S/N | 0.1212 | likely_benign | 0.1292 | benign | -0.715 | Destabilizing | 0.549 | D | 0.515 | neutral | N | 0.494597157 | None | None | N |
| S/P | 0.5412 | ambiguous | 0.5369 | ambiguous | -0.034 | Destabilizing | 0.92 | D | 0.573 | neutral | None | None | None | None | N |
| S/Q | 0.4453 | ambiguous | 0.4897 | ambiguous | -0.716 | Destabilizing | 0.85 | D | 0.542 | neutral | None | None | None | None | N |
| S/R | 0.4731 | ambiguous | 0.5706 | pathogenic | -0.619 | Destabilizing | 0.81 | D | 0.563 | neutral | N | 0.472528373 | None | None | N |
| S/T | 0.0711 | likely_benign | 0.0792 | benign | -0.641 | Destabilizing | 0.004 | N | 0.426 | neutral | N | 0.465237042 | None | None | N |
| S/V | 0.1243 | likely_benign | 0.1448 | benign | -0.034 | Destabilizing | 0.447 | N | 0.538 | neutral | None | None | None | None | N |
| S/W | 0.3033 | likely_benign | 0.3653 | ambiguous | -0.688 | Destabilizing | 0.992 | D | 0.633 | neutral | None | None | None | None | N |
| S/Y | 0.1586 | likely_benign | 0.1865 | benign | -0.37 | Destabilizing | 0.739 | D | 0.594 | 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.