Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2871 | 8836;8837;8838 | chr2:178770090;178770089;178770088 | chr2:179634817;179634816;179634815 |
| N2AB | 2871 | 8836;8837;8838 | chr2:178770090;178770089;178770088 | chr2:179634817;179634816;179634815 |
| N2A | 2871 | 8836;8837;8838 | chr2:178770090;178770089;178770088 | chr2:179634817;179634816;179634815 |
| N2B | 2825 | 8698;8699;8700 | chr2:178770090;178770089;178770088 | chr2:179634817;179634816;179634815 |
| Novex-1 | 2825 | 8698;8699;8700 | chr2:178770090;178770089;178770088 | chr2:179634817;179634816;179634815 |
| Novex-2 | 2825 | 8698;8699;8700 | chr2:178770090;178770089;178770088 | chr2:179634817;179634816;179634815 |
| Novex-3 | 2871 | 8836;8837;8838 | chr2:178770090;178770089;178770088 | chr2:179634817;179634816;179634815 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/F | None | None | 0.982 | N | 0.611 | 0.295 | 0.535102873643 | gnomAD-4.0.0 | 1.59046E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.88168E-05 | 0 | 0 | 0 | 0 |
| L/M | None | None | 0.982 | N | 0.622 | 0.388 | 0.16115917748 | gnomAD-4.0.0 | 1.59046E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.02151E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.339 | likely_benign | 0.381 | ambiguous | -0.952 | Destabilizing | 0.953 | D | 0.516 | neutral | None | None | None | None | N |
| L/C | 0.72 | likely_pathogenic | 0.8045 | pathogenic | -0.672 | Destabilizing | 0.999 | D | 0.643 | neutral | None | None | None | None | N |
| L/D | 0.8205 | likely_pathogenic | 0.8579 | pathogenic | -0.475 | Destabilizing | 0.986 | D | 0.745 | deleterious | None | None | None | None | N |
| L/E | 0.5081 | ambiguous | 0.5407 | ambiguous | -0.527 | Destabilizing | 0.973 | D | 0.713 | prob.delet. | None | None | None | None | N |
| L/F | 0.2445 | likely_benign | 0.2904 | benign | -0.717 | Destabilizing | 0.982 | D | 0.611 | neutral | N | 0.512076177 | None | None | N |
| L/G | 0.7665 | likely_pathogenic | 0.809 | pathogenic | -1.188 | Destabilizing | 0.993 | D | 0.752 | deleterious | None | None | None | None | N |
| L/H | 0.3494 | ambiguous | 0.4127 | ambiguous | -0.491 | Destabilizing | 0.998 | D | 0.725 | prob.delet. | None | None | None | None | N |
| L/I | 0.1169 | likely_benign | 0.1148 | benign | -0.421 | Destabilizing | 0.128 | N | 0.238 | neutral | None | None | None | None | N |
| L/K | 0.3958 | ambiguous | 0.4245 | ambiguous | -0.698 | Destabilizing | 0.973 | D | 0.679 | prob.neutral | None | None | None | None | N |
| L/M | 0.1224 | likely_benign | 0.1232 | benign | -0.444 | Destabilizing | 0.982 | D | 0.622 | neutral | N | 0.512590657 | None | None | N |
| L/N | 0.5554 | ambiguous | 0.6058 | pathogenic | -0.459 | Destabilizing | 0.993 | D | 0.751 | deleterious | None | None | None | None | N |
| L/P | 0.9584 | likely_pathogenic | 0.9625 | pathogenic | -0.565 | Destabilizing | 0.998 | D | 0.752 | deleterious | None | None | None | None | N |
| L/Q | 0.2132 | likely_benign | 0.2459 | benign | -0.648 | Destabilizing | 0.807 | D | 0.513 | neutral | None | None | None | None | N |
| L/R | 0.3315 | likely_benign | 0.3818 | ambiguous | -0.15 | Destabilizing | 0.986 | D | 0.713 | prob.delet. | None | None | None | None | N |
| L/S | 0.4346 | ambiguous | 0.5009 | ambiguous | -0.943 | Destabilizing | 0.982 | D | 0.655 | neutral | N | 0.495736434 | None | None | N |
| L/T | 0.2748 | likely_benign | 0.2891 | benign | -0.884 | Destabilizing | 0.986 | D | 0.597 | neutral | None | None | None | None | N |
| L/V | 0.1289 | likely_benign | 0.1315 | benign | -0.565 | Destabilizing | 0.76 | D | 0.492 | neutral | N | 0.482419256 | None | None | N |
| L/W | 0.3849 | ambiguous | 0.4794 | ambiguous | -0.772 | Destabilizing | 0.999 | D | 0.731 | prob.delet. | D | 0.577742254 | None | None | N |
| L/Y | 0.4843 | ambiguous | 0.5592 | ambiguous | -0.539 | Destabilizing | 0.998 | D | 0.656 | 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.