Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27778 | 83557;83558;83559 | chr2:178562800;178562799;178562798 | chr2:179427527;179427526;179427525 |
| N2AB | 26137 | 78634;78635;78636 | chr2:178562800;178562799;178562798 | chr2:179427527;179427526;179427525 |
| N2A | 25210 | 75853;75854;75855 | chr2:178562800;178562799;178562798 | chr2:179427527;179427526;179427525 |
| N2B | 18713 | 56362;56363;56364 | chr2:178562800;178562799;178562798 | chr2:179427527;179427526;179427525 |
| Novex-1 | 18838 | 56737;56738;56739 | chr2:178562800;178562799;178562798 | chr2:179427527;179427526;179427525 |
| Novex-2 | 18905 | 56938;56939;56940 | chr2:178562800;178562799;178562798 | chr2:179427527;179427526;179427525 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | None | None | 0.873 | N | 0.437 | 0.398 | 0.561905760881 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.75482E-04 | None | 0 | 0 | 0 | 0 | 0 |
| V/L | rs749009127  |
-0.65 | 0.18 | N | 0.301 | 0.194 | 0.41859458845 | gnomAD-2.1.1 | 1.79E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.07555E-04 | None | 0 | None | 0 | 0 | 1.41163E-04 |
| V/L | rs749009127 |
-0.65 | 0.18 | N | 0.301 | 0.194 | 0.41859458845 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 7.73994E-04 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| V/L | rs749009127 |
-0.65 | 0.18 | N | 0.301 | 0.194 | 0.41859458845 | gnomAD-4.0.0 | 7.43888E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.56509E-04 | None | 0 | 0 | 3.391E-06 | 0 | 1.60241E-05 |
| V/M | None | None | 0.97 | N | 0.631 | 0.425 | 0.558927764886 | gnomAD-4.0.0 | 6.84458E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99625E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.3233 | likely_benign | 0.3145 | benign | -1.473 | Destabilizing | 0.873 | D | 0.437 | neutral | N | 0.481994756 | None | None | N |
| V/C | 0.7468 | likely_pathogenic | 0.7315 | pathogenic | -1.397 | Destabilizing | 0.999 | D | 0.713 | prob.delet. | None | None | None | None | N |
| V/D | 0.7841 | likely_pathogenic | 0.793 | pathogenic | -1.191 | Destabilizing | 0.998 | D | 0.813 | deleterious | None | None | None | None | N |
| V/E | 0.5677 | likely_pathogenic | 0.5757 | pathogenic | -1.165 | Destabilizing | 0.983 | D | 0.759 | deleterious | N | 0.50710045 | None | None | N |
| V/F | 0.3339 | likely_benign | 0.3274 | benign | -1.15 | Destabilizing | 0.983 | D | 0.739 | prob.delet. | None | None | None | None | N |
| V/G | 0.4027 | ambiguous | 0.3943 | ambiguous | -1.798 | Destabilizing | 0.998 | D | 0.791 | deleterious | D | 0.524750632 | None | None | N |
| V/H | 0.81 | likely_pathogenic | 0.8044 | pathogenic | -1.311 | Destabilizing | 0.999 | D | 0.812 | deleterious | None | None | None | None | N |
| V/I | 0.0689 | likely_benign | 0.0692 | benign | -0.671 | Destabilizing | 0.004 | N | 0.202 | neutral | None | None | None | None | N |
| V/K | 0.5846 | likely_pathogenic | 0.5909 | pathogenic | -1.047 | Destabilizing | 0.982 | D | 0.757 | deleterious | None | None | None | None | N |
| V/L | 0.2578 | likely_benign | 0.2499 | benign | -0.671 | Destabilizing | 0.18 | N | 0.301 | neutral | N | 0.470941165 | None | None | N |
| V/M | 0.1666 | likely_benign | 0.1666 | benign | -0.787 | Destabilizing | 0.97 | D | 0.631 | neutral | N | 0.492808083 | None | None | N |
| V/N | 0.537 | ambiguous | 0.5364 | ambiguous | -0.937 | Destabilizing | 0.962 | D | 0.811 | deleterious | None | None | None | None | N |
| V/P | 0.8493 | likely_pathogenic | 0.8459 | pathogenic | -0.905 | Destabilizing | 0.962 | D | 0.781 | deleterious | None | None | None | None | N |
| V/Q | 0.5253 | ambiguous | 0.5163 | ambiguous | -1.09 | Destabilizing | 0.992 | D | 0.775 | deleterious | None | None | None | None | N |
| V/R | 0.5788 | likely_pathogenic | 0.5721 | pathogenic | -0.666 | Destabilizing | 0.997 | D | 0.809 | deleterious | None | None | None | None | N |
| V/S | 0.4356 | ambiguous | 0.4149 | ambiguous | -1.551 | Destabilizing | 0.985 | D | 0.753 | deleterious | None | None | None | None | N |
| V/T | 0.2833 | likely_benign | 0.2731 | benign | -1.407 | Destabilizing | 0.786 | D | 0.514 | neutral | None | None | None | None | N |
| V/W | 0.8924 | likely_pathogenic | 0.8895 | pathogenic | -1.29 | Destabilizing | 1.0 | D | 0.807 | deleterious | None | None | None | None | N |
| V/Y | 0.7092 | likely_pathogenic | 0.6932 | pathogenic | -0.966 | Destabilizing | 0.997 | D | 0.755 | 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.