Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14621 | 44086;44087;44088 | chr2:178631187;178631186;178631185 | chr2:179495914;179495913;179495912 |
| N2AB | 12980 | 39163;39164;39165 | chr2:178631187;178631186;178631185 | chr2:179495914;179495913;179495912 |
| N2A | 12053 | 36382;36383;36384 | chr2:178631187;178631186;178631185 | chr2:179495914;179495913;179495912 |
| N2B | 5556 | 16891;16892;16893 | chr2:178631187;178631186;178631185 | chr2:179495914;179495913;179495912 |
| Novex-1 | 5681 | 17266;17267;17268 | chr2:178631187;178631186;178631185 | chr2:179495914;179495913;179495912 |
| Novex-2 | 5748 | 17467;17468;17469 | chr2:178631187;178631186;178631185 | chr2:179495914;179495913;179495912 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/N | rs374032491  |
0.508 | 1.0 | N | 0.637 | 0.357 | None | gnomAD-2.1.1 | 7.66E-05 | None | None | None | None | N | None | 0 | 0 | None | 1.39331E-03 | 0 | None | 0 | None | 0 | 3.56E-05 | 1.66556E-04 |
| D/N | rs374032491 |
0.508 | 1.0 | N | 0.637 | 0.357 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 2.88351E-04 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/N | rs374032491 |
0.508 | 1.0 | N | 0.637 | 0.357 | None | gnomAD-4.0.0 | 2.97557E-05 | None | None | None | None | N | None | 0 | 0 | None | 1.3519E-03 | 0 | None | 0 | 0 | 1.6955E-06 | 0 | 9.61415E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.5094 | ambiguous | 0.4409 | ambiguous | -0.596 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | D | 0.587279989 | None | None | N |
| D/C | 0.8979 | likely_pathogenic | 0.8725 | pathogenic | -0.208 | Destabilizing | 1.0 | D | 0.647 | neutral | None | None | None | None | N |
| D/E | 0.5194 | ambiguous | 0.4603 | ambiguous | -0.395 | Destabilizing | 1.0 | D | 0.431 | neutral | N | 0.496692336 | None | None | N |
| D/F | 0.9051 | likely_pathogenic | 0.8785 | pathogenic | -0.24 | Destabilizing | 1.0 | D | 0.652 | neutral | None | None | None | None | N |
| D/G | 0.2572 | likely_benign | 0.2201 | benign | -0.856 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | N | 0.448014946 | None | None | N |
| D/H | 0.7291 | likely_pathogenic | 0.6835 | pathogenic | -0.177 | Destabilizing | 1.0 | D | 0.631 | neutral | D | 0.696646878 | None | None | N |
| D/I | 0.9012 | likely_pathogenic | 0.8675 | pathogenic | 0.066 | Stabilizing | 1.0 | D | 0.675 | neutral | None | None | None | None | N |
| D/K | 0.8246 | likely_pathogenic | 0.7769 | pathogenic | None | Stabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | N |
| D/L | 0.8484 | likely_pathogenic | 0.8082 | pathogenic | 0.066 | Stabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | N |
| D/M | 0.946 | likely_pathogenic | 0.929 | pathogenic | 0.298 | Stabilizing | 1.0 | D | 0.646 | neutral | None | None | None | None | N |
| D/N | 0.1591 | likely_benign | 0.1545 | benign | -0.452 | Destabilizing | 1.0 | D | 0.637 | neutral | N | 0.427871443 | None | None | N |
| D/P | 0.9887 | likely_pathogenic | 0.9867 | pathogenic | -0.132 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | N |
| D/Q | 0.8269 | likely_pathogenic | 0.7837 | pathogenic | -0.371 | Destabilizing | 1.0 | D | 0.67 | neutral | None | None | None | None | N |
| D/R | 0.8236 | likely_pathogenic | 0.7785 | pathogenic | 0.257 | Stabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | N |
| D/S | 0.3451 | ambiguous | 0.3078 | benign | -0.596 | Destabilizing | 1.0 | D | 0.661 | neutral | None | None | None | None | N |
| D/T | 0.7912 | likely_pathogenic | 0.7492 | pathogenic | -0.382 | Destabilizing | 1.0 | D | 0.72 | prob.delet. | None | None | None | None | N |
| D/V | 0.7387 | likely_pathogenic | 0.6683 | pathogenic | -0.132 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | D | 0.696761879 | None | None | N |
| D/W | 0.9735 | likely_pathogenic | 0.9638 | pathogenic | 0.009 | Stabilizing | 1.0 | D | 0.646 | neutral | None | None | None | None | N |
| D/Y | 0.4619 | ambiguous | 0.4056 | ambiguous | 0.017 | Stabilizing | 1.0 | D | 0.639 | neutral | D | 0.659305299 | 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.