Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17902 | 53929;53930;53931 | chr2:178605591;178605590;178605589 | chr2:179470318;179470317;179470316 |
| N2AB | 16261 | 49006;49007;49008 | chr2:178605591;178605590;178605589 | chr2:179470318;179470317;179470316 |
| N2A | 15334 | 46225;46226;46227 | chr2:178605591;178605590;178605589 | chr2:179470318;179470317;179470316 |
| N2B | 8837 | 26734;26735;26736 | chr2:178605591;178605590;178605589 | chr2:179470318;179470317;179470316 |
| Novex-1 | 8962 | 27109;27110;27111 | chr2:178605591;178605590;178605589 | chr2:179470318;179470317;179470316 |
| Novex-2 | 9029 | 27310;27311;27312 | chr2:178605591;178605590;178605589 | chr2:179470318;179470317;179470316 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/Q | rs781600329  |
-1.024 | 0.873 | N | 0.481 | 0.311 | 0.177238962908 | gnomAD-2.1.1 | 3.22E-05 | None | None | None | None | N | None | 0 | 0 | None | 9.97E-05 | 0 | None | 1.63473E-04 | None | 0 | 1.78E-05 | 0 |
| R/Q | rs781600329 |
-1.024 | 0.873 | N | 0.481 | 0.311 | 0.177238962908 | gnomAD-4.0.0 | 8.21778E-06 | None | None | None | None | N | None | 0 | 0 | None | 3.83406E-05 | 0 | None | 0 | 0 | 5.40107E-06 | 5.80437E-05 | 0 |
| R/W | rs748647255 |
-0.739 | 0.998 | N | 0.629 | 0.412 | 0.340992353424 | gnomAD-2.1.1 | 1.07E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.16E-05 | None | 0 | None | 0 | 1.57E-05 | 0 |
| R/W | rs748647255 |
-0.739 | 0.998 | N | 0.629 | 0.412 | 0.340992353424 | gnomAD-3.1.2 | 6.6E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/W | rs748647255 |
-0.739 | 0.998 | N | 0.629 | 0.412 | 0.340992353424 | gnomAD-4.0.0 | 3.72431E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 4.47928E-05 | None | 0 | 0 | 3.3945E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.8851 | likely_pathogenic | 0.8957 | pathogenic | -1.663 | Destabilizing | 0.25 | N | 0.403 | neutral | None | None | None | None | N |
| R/C | 0.3333 | likely_benign | 0.3382 | benign | -1.666 | Destabilizing | 0.992 | D | 0.618 | neutral | None | None | None | None | N |
| R/D | 0.9886 | likely_pathogenic | 0.9901 | pathogenic | -0.703 | Destabilizing | 0.617 | D | 0.555 | neutral | None | None | None | None | N |
| R/E | 0.8845 | likely_pathogenic | 0.9041 | pathogenic | -0.516 | Destabilizing | 0.4 | N | 0.483 | neutral | None | None | None | None | N |
| R/F | 0.9036 | likely_pathogenic | 0.9331 | pathogenic | -1.029 | Destabilizing | 0.972 | D | 0.601 | neutral | None | None | None | None | N |
| R/G | 0.8299 | likely_pathogenic | 0.8311 | pathogenic | -1.991 | Destabilizing | 0.004 | N | 0.341 | neutral | N | 0.496794101 | None | None | N |
| R/H | 0.3566 | ambiguous | 0.3721 | ambiguous | -1.971 | Destabilizing | 0.972 | D | 0.519 | neutral | None | None | None | None | N |
| R/I | 0.7771 | likely_pathogenic | 0.8442 | pathogenic | -0.73 | Destabilizing | 0.972 | D | 0.616 | neutral | None | None | None | None | N |
| R/K | 0.1639 | likely_benign | 0.1767 | benign | -1.331 | Destabilizing | 0.003 | N | 0.141 | neutral | None | None | None | None | N |
| R/L | 0.5999 | likely_pathogenic | 0.7302 | pathogenic | -0.73 | Destabilizing | 0.863 | D | 0.526 | neutral | N | 0.482208565 | None | None | N |
| R/M | 0.6179 | likely_pathogenic | 0.7059 | pathogenic | -1.233 | Destabilizing | 0.972 | D | 0.546 | neutral | None | None | None | None | N |
| R/N | 0.9547 | likely_pathogenic | 0.9567 | pathogenic | -1.078 | Destabilizing | 0.617 | D | 0.439 | neutral | None | None | None | None | N |
| R/P | 0.9961 | likely_pathogenic | 0.997 | pathogenic | -1.027 | Destabilizing | 0.985 | D | 0.606 | neutral | N | 0.515151846 | None | None | N |
| R/Q | 0.2152 | likely_benign | 0.2284 | benign | -1.016 | Destabilizing | 0.873 | D | 0.481 | neutral | N | 0.515998644 | None | None | N |
| R/S | 0.9416 | likely_pathogenic | 0.9434 | pathogenic | -1.928 | Destabilizing | 0.617 | D | 0.511 | neutral | None | None | None | None | N |
| R/T | 0.887 | likely_pathogenic | 0.8998 | pathogenic | -1.545 | Destabilizing | 0.766 | D | 0.476 | neutral | None | None | None | None | N |
| R/V | 0.8041 | likely_pathogenic | 0.8564 | pathogenic | -1.027 | Destabilizing | 0.766 | D | 0.6 | neutral | None | None | None | None | N |
| R/W | 0.6503 | likely_pathogenic | 0.7106 | pathogenic | -0.595 | Destabilizing | 0.998 | D | 0.629 | neutral | N | 0.484423838 | None | None | N |
| R/Y | 0.8099 | likely_pathogenic | 0.8363 | pathogenic | -0.391 | Destabilizing | 0.972 | D | 0.602 | 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.