Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21018 | 63277;63278;63279 | chr2:178588673;178588672;178588671 | chr2:179453400;179453399;179453398 |
| N2AB | 19377 | 58354;58355;58356 | chr2:178588673;178588672;178588671 | chr2:179453400;179453399;179453398 |
| N2A | 18450 | 55573;55574;55575 | chr2:178588673;178588672;178588671 | chr2:179453400;179453399;179453398 |
| N2B | 11953 | 36082;36083;36084 | chr2:178588673;178588672;178588671 | chr2:179453400;179453399;179453398 |
| Novex-1 | 12078 | 36457;36458;36459 | chr2:178588673;178588672;178588671 | chr2:179453400;179453399;179453398 |
| Novex-2 | 12145 | 36658;36659;36660 | chr2:178588673;178588672;178588671 | chr2:179453400;179453399;179453398 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/S | rs2049585221  |
None | 0.864 | N | 0.647 | 0.389 | 0.645807989578 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/S | rs2049585221 |
None | 0.864 | N | 0.647 | 0.389 | 0.645807989578 | gnomAD-4.0.0 | 6.58189E-06 | None | None | None | None | N | None | 2.41593E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs1288233039 |
-0.949 | 0.002 | N | 0.259 | 0.094 | 0.209622950755 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| I/V | rs1288233039 |
-0.949 | 0.002 | N | 0.259 | 0.094 | 0.209622950755 | gnomAD-4.0.0 | 3.18568E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.7221E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.6795 | likely_pathogenic | 0.5574 | ambiguous | -1.952 | Destabilizing | 0.547 | D | 0.49 | neutral | None | None | None | None | N |
| I/C | 0.8044 | likely_pathogenic | 0.7038 | pathogenic | -0.998 | Destabilizing | 0.985 | D | 0.65 | neutral | None | None | None | None | N |
| I/D | 0.9733 | likely_pathogenic | 0.9403 | pathogenic | -1.682 | Destabilizing | 0.945 | D | 0.734 | prob.delet. | None | None | None | None | N |
| I/E | 0.9474 | likely_pathogenic | 0.9016 | pathogenic | -1.539 | Destabilizing | 0.945 | D | 0.719 | prob.delet. | None | None | None | None | N |
| I/F | 0.3508 | ambiguous | 0.2889 | benign | -1.125 | Destabilizing | 0.864 | D | 0.655 | neutral | N | 0.469127059 | None | None | N |
| I/G | 0.8922 | likely_pathogenic | 0.7736 | pathogenic | -2.414 | Highly Destabilizing | 0.945 | D | 0.715 | prob.delet. | None | None | None | None | N |
| I/H | 0.866 | likely_pathogenic | 0.7602 | pathogenic | -1.751 | Destabilizing | 0.995 | D | 0.725 | prob.delet. | None | None | None | None | N |
| I/K | 0.8461 | likely_pathogenic | 0.7231 | pathogenic | -1.266 | Destabilizing | 0.945 | D | 0.722 | prob.delet. | None | None | None | None | N |
| I/L | 0.1348 | likely_benign | 0.1188 | benign | -0.67 | Destabilizing | 0.141 | N | 0.411 | neutral | N | 0.49671945 | None | None | N |
| I/M | 0.193 | likely_benign | 0.1679 | benign | -0.48 | Destabilizing | 0.864 | D | 0.635 | neutral | N | 0.475710424 | None | None | N |
| I/N | 0.6804 | likely_pathogenic | 0.4861 | ambiguous | -1.344 | Destabilizing | 0.975 | D | 0.743 | deleterious | N | 0.478656031 | None | None | N |
| I/P | 0.9649 | likely_pathogenic | 0.9311 | pathogenic | -1.072 | Destabilizing | 0.981 | D | 0.743 | deleterious | None | None | None | None | N |
| I/Q | 0.8392 | likely_pathogenic | 0.7163 | pathogenic | -1.331 | Destabilizing | 0.981 | D | 0.736 | prob.delet. | None | None | None | None | N |
| I/R | 0.8132 | likely_pathogenic | 0.6726 | pathogenic | -0.895 | Destabilizing | 0.945 | D | 0.741 | deleterious | None | None | None | None | N |
| I/S | 0.662 | likely_pathogenic | 0.4864 | ambiguous | -2.044 | Highly Destabilizing | 0.864 | D | 0.647 | neutral | N | 0.505258788 | None | None | N |
| I/T | 0.57 | likely_pathogenic | 0.4312 | ambiguous | -1.773 | Destabilizing | 0.645 | D | 0.617 | neutral | N | 0.460678505 | None | None | N |
| I/V | 0.0861 | likely_benign | 0.0893 | benign | -1.072 | Destabilizing | 0.002 | N | 0.259 | neutral | N | 0.410657903 | None | None | N |
| I/W | 0.9523 | likely_pathogenic | 0.9235 | pathogenic | -1.426 | Destabilizing | 0.995 | D | 0.69 | prob.neutral | None | None | None | None | N |
| I/Y | 0.8387 | likely_pathogenic | 0.746 | pathogenic | -1.112 | Destabilizing | 0.945 | D | 0.681 | prob.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.