Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28806 | 86641;86642;86643 | chr2:178559716;178559715;178559714 | chr2:179424443;179424442;179424441 |
| N2AB | 27165 | 81718;81719;81720 | chr2:178559716;178559715;178559714 | chr2:179424443;179424442;179424441 |
| N2A | 26238 | 78937;78938;78939 | chr2:178559716;178559715;178559714 | chr2:179424443;179424442;179424441 |
| N2B | 19741 | 59446;59447;59448 | chr2:178559716;178559715;178559714 | chr2:179424443;179424442;179424441 |
| Novex-1 | 19866 | 59821;59822;59823 | chr2:178559716;178559715;178559714 | chr2:179424443;179424442;179424441 |
| Novex-2 | 19933 | 60022;60023;60024 | chr2:178559716;178559715;178559714 | chr2:179424443;179424442;179424441 |
| 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 | rs1060500445  |
-0.708 | 0.001 | N | 0.303 | 0.163 | 0.256283259241 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 4.78011E-04 |
| S/C | rs1060500445 |
-0.708 | 0.001 | N | 0.303 | 0.163 | 0.256283259241 | gnomAD-4.0.0 | 6.57272E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 4.78011E-04 |
| S/F | rs1060500445 |
None | 0.484 | N | 0.533 | 0.147 | 0.444505407614 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 6.33473E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.089 | likely_benign | 0.0917 | benign | -0.431 | Destabilizing | 0.012 | N | 0.295 | neutral | D | 0.524879991 | None | None | N |
| S/C | 0.0913 | likely_benign | 0.0929 | benign | -0.333 | Destabilizing | 0.001 | N | 0.303 | neutral | N | 0.487493663 | None | None | N |
| S/D | 0.2941 | likely_benign | 0.3487 | ambiguous | 0.387 | Stabilizing | 0.081 | N | 0.377 | neutral | None | None | None | None | N |
| S/E | 0.4301 | ambiguous | 0.476 | ambiguous | 0.336 | Stabilizing | 0.149 | N | 0.375 | neutral | None | None | None | None | N |
| S/F | 0.1376 | likely_benign | 0.1415 | benign | -0.8 | Destabilizing | 0.484 | N | 0.533 | neutral | N | 0.517436731 | None | None | N |
| S/G | 0.0881 | likely_benign | 0.0957 | benign | -0.611 | Destabilizing | 0.035 | N | 0.372 | neutral | None | None | None | None | N |
| S/H | 0.2329 | likely_benign | 0.2655 | benign | -1.034 | Destabilizing | 0.555 | D | 0.45 | neutral | None | None | None | None | N |
| S/I | 0.1498 | likely_benign | 0.158 | benign | -0.077 | Destabilizing | 0.235 | N | 0.514 | neutral | None | None | None | None | N |
| S/K | 0.4871 | ambiguous | 0.5557 | ambiguous | -0.45 | Destabilizing | 0.149 | N | 0.377 | neutral | None | None | None | None | N |
| S/L | 0.0945 | likely_benign | 0.0957 | benign | -0.077 | Destabilizing | 0.081 | N | 0.525 | neutral | None | None | None | None | N |
| S/M | 0.1455 | likely_benign | 0.1534 | benign | 0.003 | Stabilizing | 0.555 | D | 0.451 | neutral | None | None | None | None | N |
| S/N | 0.1009 | likely_benign | 0.1143 | benign | -0.278 | Destabilizing | 0.001 | N | 0.223 | neutral | None | None | None | None | N |
| S/P | 0.5664 | likely_pathogenic | 0.6242 | pathogenic | -0.162 | Destabilizing | 0.484 | N | 0.44 | neutral | N | 0.498342989 | None | None | N |
| S/Q | 0.3645 | ambiguous | 0.4006 | ambiguous | -0.436 | Destabilizing | 0.555 | D | 0.423 | neutral | None | None | None | None | N |
| S/R | 0.4158 | ambiguous | 0.4771 | ambiguous | -0.314 | Destabilizing | 0.38 | N | 0.429 | neutral | None | None | None | None | N |
| S/T | 0.0625 | likely_benign | 0.0674 | benign | -0.37 | Destabilizing | None | N | 0.173 | neutral | N | 0.455868197 | None | None | N |
| S/V | 0.1577 | likely_benign | 0.1652 | benign | -0.162 | Destabilizing | 0.081 | N | 0.548 | neutral | None | None | None | None | N |
| S/W | 0.2771 | likely_benign | 0.2977 | benign | -0.801 | Destabilizing | 0.935 | D | 0.577 | neutral | None | None | None | None | N |
| S/Y | 0.1309 | likely_benign | 0.1412 | benign | -0.518 | Destabilizing | 0.484 | N | 0.535 | neutral | N | 0.489519411 | 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.