Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28145 | 84658;84659;84660 | chr2:178561699;178561698;178561697 | chr2:179426426;179426425;179426424 |
| N2AB | 26504 | 79735;79736;79737 | chr2:178561699;178561698;178561697 | chr2:179426426;179426425;179426424 |
| N2A | 25577 | 76954;76955;76956 | chr2:178561699;178561698;178561697 | chr2:179426426;179426425;179426424 |
| N2B | 19080 | 57463;57464;57465 | chr2:178561699;178561698;178561697 | chr2:179426426;179426425;179426424 |
| Novex-1 | 19205 | 57838;57839;57840 | chr2:178561699;178561698;178561697 | chr2:179426426;179426425;179426424 |
| Novex-2 | 19272 | 58039;58040;58041 | chr2:178561699;178561698;178561697 | chr2:179426426;179426425;179426424 |
| 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/V | rs765357961  |
0.057 | None | N | 0.14 | 0.139 | 0.377097596864 | gnomAD-2.1.1 | 4.07E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.99E-06 | 0 |
| A/V | rs765357961 |
0.057 | None | N | 0.14 | 0.139 | 0.377097596864 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 5.88E-05 | 0 | 0 |
| A/V | rs765357961 |
0.057 | None | N | 0.14 | 0.139 | 0.377097596864 | gnomAD-4.0.0 | 2.23817E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.97502E-05 | 0 | 1.60756E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.3045 | likely_benign | 0.2893 | benign | -0.826 | Destabilizing | 0.747 | D | 0.417 | neutral | None | None | None | None | N |
| A/D | 0.3196 | likely_benign | 0.2517 | benign | -0.554 | Destabilizing | 0.026 | N | 0.427 | neutral | N | 0.444557046 | None | None | N |
| A/E | 0.2829 | likely_benign | 0.2454 | benign | -0.698 | Destabilizing | 0.035 | N | 0.414 | neutral | None | None | None | None | N |
| A/F | 0.3153 | likely_benign | 0.2819 | benign | -0.941 | Destabilizing | 0.112 | N | 0.572 | neutral | None | None | None | None | N |
| A/G | 0.1368 | likely_benign | 0.1263 | benign | -0.507 | Destabilizing | 0.006 | N | 0.292 | neutral | N | 0.478842978 | None | None | N |
| A/H | 0.4137 | ambiguous | 0.3505 | ambiguous | -0.503 | Destabilizing | 0.439 | N | 0.459 | neutral | None | None | None | None | N |
| A/I | 0.2029 | likely_benign | 0.1932 | benign | -0.389 | Destabilizing | 0.018 | N | 0.383 | neutral | None | None | None | None | N |
| A/K | 0.4183 | ambiguous | 0.3408 | ambiguous | -0.752 | Destabilizing | 0.035 | N | 0.423 | neutral | None | None | None | None | N |
| A/L | 0.1573 | likely_benign | 0.1498 | benign | -0.389 | Destabilizing | 0.007 | N | 0.337 | neutral | None | None | None | None | N |
| A/M | 0.2129 | likely_benign | 0.2014 | benign | -0.373 | Destabilizing | 0.204 | N | 0.397 | neutral | None | None | None | None | N |
| A/N | 0.2377 | likely_benign | 0.2109 | benign | -0.436 | Destabilizing | 0.035 | N | 0.541 | neutral | None | None | None | None | N |
| A/P | 0.0922 | likely_benign | 0.0929 | benign | -0.364 | Destabilizing | None | N | 0.15 | neutral | N | 0.35870893 | None | None | N |
| A/Q | 0.3272 | likely_benign | 0.2858 | benign | -0.729 | Destabilizing | 0.204 | N | 0.514 | neutral | None | None | None | None | N |
| A/R | 0.3689 | ambiguous | 0.3049 | benign | -0.259 | Destabilizing | 0.112 | N | 0.516 | neutral | None | None | None | None | N |
| A/S | 0.0877 | likely_benign | 0.0861 | benign | -0.677 | Destabilizing | None | N | 0.095 | neutral | N | 0.424411061 | None | None | N |
| A/T | 0.0864 | likely_benign | 0.0837 | benign | -0.739 | Destabilizing | 0.006 | N | 0.283 | neutral | N | 0.451634947 | None | None | N |
| A/V | 0.1085 | likely_benign | 0.1077 | benign | -0.364 | Destabilizing | None | N | 0.14 | neutral | N | 0.447557279 | None | None | N |
| A/W | 0.6581 | likely_pathogenic | 0.5972 | pathogenic | -1.079 | Destabilizing | 0.747 | D | 0.576 | neutral | None | None | None | None | N |
| A/Y | 0.4189 | ambiguous | 0.3632 | ambiguous | -0.731 | Destabilizing | 0.204 | N | 0.565 | 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.