Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25516 | 76771;76772;76773 | chr2:178569586;178569585;178569584 | chr2:179434313;179434312;179434311 |
| N2AB | 23875 | 71848;71849;71850 | chr2:178569586;178569585;178569584 | chr2:179434313;179434312;179434311 |
| N2A | 22948 | 69067;69068;69069 | chr2:178569586;178569585;178569584 | chr2:179434313;179434312;179434311 |
| N2B | 16451 | 49576;49577;49578 | chr2:178569586;178569585;178569584 | chr2:179434313;179434312;179434311 |
| Novex-1 | 16576 | 49951;49952;49953 | chr2:178569586;178569585;178569584 | chr2:179434313;179434312;179434311 |
| Novex-2 | 16643 | 50152;50153;50154 | chr2:178569586;178569585;178569584 | chr2:179434313;179434312;179434311 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/I | rs752300467  |
-0.674 | 0.992 | N | 0.529 | 0.276 | 0.317958651998 | gnomAD-2.1.1 | 1.22E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 9.83E-05 | None | 0 | 0 | 0 |
| L/I | rs752300467 |
-0.674 | 0.992 | N | 0.529 | 0.276 | 0.317958651998 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07641E-04 | 0 |
| L/I | rs752300467 |
-0.674 | 0.992 | N | 0.529 | 0.276 | 0.317958651998 | gnomAD-4.0.0 | 6.20099E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.09878E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.8468 | likely_pathogenic | 0.8498 | pathogenic | -1.087 | Destabilizing | 0.997 | D | 0.627 | neutral | None | None | None | None | N |
| L/C | 0.8518 | likely_pathogenic | 0.8641 | pathogenic | -0.863 | Destabilizing | 1.0 | D | 0.758 | deleterious | None | None | None | None | N |
| L/D | 0.9821 | likely_pathogenic | 0.9837 | pathogenic | -0.448 | Destabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | None | N |
| L/E | 0.9429 | likely_pathogenic | 0.9451 | pathogenic | -0.457 | Destabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | N |
| L/F | 0.376 | ambiguous | 0.4097 | ambiguous | -0.689 | Destabilizing | 0.999 | D | 0.759 | deleterious | None | None | None | None | N |
| L/G | 0.9251 | likely_pathogenic | 0.9222 | pathogenic | -1.36 | Destabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | N |
| L/H | 0.8056 | likely_pathogenic | 0.8044 | pathogenic | -0.505 | Destabilizing | 1.0 | D | 0.79 | deleterious | None | None | None | None | N |
| L/I | 0.3414 | ambiguous | 0.3636 | ambiguous | -0.437 | Destabilizing | 0.992 | D | 0.529 | neutral | N | 0.489162277 | None | None | N |
| L/K | 0.8955 | likely_pathogenic | 0.89 | pathogenic | -0.762 | Destabilizing | 1.0 | D | 0.746 | deleterious | None | None | None | None | N |
| L/M | 0.1798 | likely_benign | 0.1929 | benign | -0.579 | Destabilizing | 0.967 | D | 0.343 | neutral | None | None | None | None | N |
| L/N | 0.8839 | likely_pathogenic | 0.8853 | pathogenic | -0.631 | Destabilizing | 1.0 | D | 0.796 | deleterious | None | None | None | None | N |
| L/P | 0.9775 | likely_pathogenic | 0.9774 | pathogenic | -0.622 | Destabilizing | 1.0 | D | 0.793 | deleterious | D | 0.52891964 | None | None | N |
| L/Q | 0.7362 | likely_pathogenic | 0.7344 | pathogenic | -0.749 | Destabilizing | 0.999 | D | 0.773 | deleterious | D | 0.52866615 | None | None | N |
| L/R | 0.8672 | likely_pathogenic | 0.8585 | pathogenic | -0.255 | Destabilizing | 0.999 | D | 0.761 | deleterious | D | 0.52866615 | None | None | N |
| L/S | 0.8922 | likely_pathogenic | 0.9032 | pathogenic | -1.184 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | N |
| L/T | 0.8207 | likely_pathogenic | 0.8294 | pathogenic | -1.069 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | N |
| L/V | 0.3997 | ambiguous | 0.4173 | ambiguous | -0.622 | Destabilizing | 0.992 | D | 0.545 | neutral | N | 0.486124083 | None | None | N |
| L/W | 0.6719 | likely_pathogenic | 0.6904 | pathogenic | -0.735 | Destabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | N |
| L/Y | 0.6945 | likely_pathogenic | 0.7141 | pathogenic | -0.511 | Destabilizing | 1.0 | D | 0.788 | deleterious | 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.