Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14398 | 43417;43418;43419 | chr2:178632939;178632938;178632937 | chr2:179497666;179497665;179497664 |
| N2AB | 12757 | 38494;38495;38496 | chr2:178632939;178632938;178632937 | chr2:179497666;179497665;179497664 |
| N2A | 11830 | 35713;35714;35715 | chr2:178632939;178632938;178632937 | chr2:179497666;179497665;179497664 |
| N2B | 5333 | 16222;16223;16224 | chr2:178632939;178632938;178632937 | chr2:179497666;179497665;179497664 |
| Novex-1 | 5458 | 16597;16598;16599 | chr2:178632939;178632938;178632937 | chr2:179497666;179497665;179497664 |
| Novex-2 | 5525 | 16798;16799;16800 | chr2:178632939;178632938;178632937 | chr2:179497666;179497665;179497664 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/S | None | None | 0.007 | N | 0.253 | 0.072 | 0.0954503805726 | gnomAD-4.0.0 | 6.84668E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.52309E-05 | None | 0 | 0 | 0 | 0 | 0 |
| A/T | rs536808297  |
-0.619 | 0.376 | N | 0.563 | 0.08 | 0.173771789658 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/T | rs536808297 |
-0.619 | 0.376 | N | 0.563 | 0.08 | 0.173771789658 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| A/T | rs536808297 |
-0.619 | 0.376 | N | 0.563 | 0.08 | 0.173771789658 | gnomAD-4.0.0 | 1.86017E-06 | None | None | None | None | N | None | 2.66802E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 8.47965E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.5924 | likely_pathogenic | 0.5374 | ambiguous | -0.792 | Destabilizing | 0.992 | D | 0.583 | neutral | None | None | None | None | N |
| A/D | 0.4633 | ambiguous | 0.3973 | ambiguous | -0.754 | Destabilizing | 0.615 | D | 0.689 | prob.delet. | None | None | None | None | N |
| A/E | 0.3282 | likely_benign | 0.2698 | benign | -0.896 | Destabilizing | 0.376 | N | 0.607 | neutral | N | 0.414855553 | None | None | N |
| A/F | 0.4054 | ambiguous | 0.3552 | ambiguous | -1.135 | Destabilizing | 0.919 | D | 0.705 | prob.delet. | None | None | None | None | N |
| A/G | 0.2464 | likely_benign | 0.2142 | benign | -0.666 | Destabilizing | 0.199 | N | 0.555 | neutral | N | 0.431739657 | None | None | N |
| A/H | 0.5432 | ambiguous | 0.4721 | ambiguous | -0.74 | Destabilizing | 0.977 | D | 0.704 | prob.delet. | None | None | None | None | N |
| A/I | 0.3436 | ambiguous | 0.3008 | benign | -0.49 | Destabilizing | 0.919 | D | 0.641 | neutral | None | None | None | None | N |
| A/K | 0.4611 | ambiguous | 0.3845 | ambiguous | -0.815 | Destabilizing | 0.444 | N | 0.557 | neutral | None | None | None | None | N |
| A/L | 0.3014 | likely_benign | 0.2525 | benign | -0.49 | Destabilizing | 0.615 | D | 0.557 | neutral | None | None | None | None | N |
| A/M | 0.3113 | likely_benign | 0.2741 | benign | -0.351 | Destabilizing | 0.992 | D | 0.613 | neutral | None | None | None | None | N |
| A/N | 0.368 | ambiguous | 0.3186 | benign | -0.456 | Destabilizing | 0.737 | D | 0.707 | prob.delet. | None | None | None | None | N |
| A/P | 0.8309 | likely_pathogenic | 0.7765 | pathogenic | -0.48 | Destabilizing | 0.895 | D | 0.638 | neutral | N | 0.434635182 | None | None | N |
| A/Q | 0.3772 | ambiguous | 0.307 | benign | -0.773 | Destabilizing | 0.047 | N | 0.352 | neutral | None | None | None | None | N |
| A/R | 0.3925 | ambiguous | 0.3457 | ambiguous | -0.333 | Destabilizing | 0.737 | D | 0.637 | neutral | None | None | None | None | N |
| A/S | 0.096 | likely_benign | 0.093 | benign | -0.69 | Destabilizing | 0.007 | N | 0.253 | neutral | N | 0.302774285 | None | None | N |
| A/T | 0.0939 | likely_benign | 0.0887 | benign | -0.756 | Destabilizing | 0.376 | N | 0.563 | neutral | N | 0.391175716 | None | None | N |
| A/V | 0.1629 | likely_benign | 0.1472 | benign | -0.48 | Destabilizing | 0.546 | D | 0.583 | neutral | N | 0.429285775 | None | None | N |
| A/W | 0.848 | likely_pathogenic | 0.8154 | pathogenic | -1.279 | Destabilizing | 0.992 | D | 0.78 | deleterious | None | None | None | None | N |
| A/Y | 0.6013 | likely_pathogenic | 0.5463 | ambiguous | -0.924 | Destabilizing | 0.972 | D | 0.707 | 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.