Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33485 | 100678;100679;100680 | chr2:178536294;178536293;178536292 | chr2:179401021;179401020;179401019 |
| N2AB | 31844 | 95755;95756;95757 | chr2:178536294;178536293;178536292 | chr2:179401021;179401020;179401019 |
| N2A | 30917 | 92974;92975;92976 | chr2:178536294;178536293;178536292 | chr2:179401021;179401020;179401019 |
| N2B | 24420 | 73483;73484;73485 | chr2:178536294;178536293;178536292 | chr2:179401021;179401020;179401019 |
| Novex-1 | 24545 | 73858;73859;73860 | chr2:178536294;178536293;178536292 | chr2:179401021;179401020;179401019 |
| Novex-2 | 24612 | 74059;74060;74061 | chr2:178536294;178536293;178536292 | chr2:179401021;179401020;179401019 |
| 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/T | rs369247146  |
-2.755 | 0.03 | N | 0.653 | 0.107 | 0.364141725642 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| I/T | rs369247146 |
-2.755 | 0.03 | N | 0.653 | 0.107 | 0.364141725642 | gnomAD-4.0.0 | 1.59164E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43312E-05 | 0 |
| I/V | rs2154137339 |
None | None | N | 0.135 | 0.091 | 0.0920862733494 | gnomAD-4.0.0 | 1.59157E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85848E-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 | 0.2882 | likely_benign | 0.2489 | benign | -2.075 | Highly Destabilizing | None | N | 0.375 | neutral | None | None | None | None | N |
| I/C | 0.6176 | likely_pathogenic | 0.5424 | ambiguous | -1.237 | Destabilizing | 0.366 | N | 0.619 | neutral | None | None | None | None | N |
| I/D | 0.8364 | likely_pathogenic | 0.8302 | pathogenic | -1.921 | Destabilizing | 0.221 | N | 0.683 | prob.neutral | None | None | None | None | N |
| I/E | 0.7066 | likely_pathogenic | 0.6883 | pathogenic | -1.829 | Destabilizing | 0.075 | N | 0.691 | prob.delet. | None | None | None | None | N |
| I/F | 0.2269 | likely_benign | 0.1972 | benign | -1.281 | Destabilizing | 0.177 | N | 0.63 | neutral | N | 0.489521332 | None | None | N |
| I/G | 0.6482 | likely_pathogenic | 0.5743 | pathogenic | -2.483 | Highly Destabilizing | 0.039 | N | 0.689 | prob.delet. | None | None | None | None | N |
| I/H | 0.7185 | likely_pathogenic | 0.6712 | pathogenic | -1.666 | Destabilizing | 0.869 | D | 0.693 | prob.delet. | None | None | None | None | N |
| I/K | 0.5825 | likely_pathogenic | 0.5623 | ambiguous | -1.697 | Destabilizing | 0.221 | N | 0.683 | prob.neutral | None | None | None | None | N |
| I/L | 0.1577 | likely_benign | 0.1264 | benign | -0.97 | Destabilizing | 0.005 | N | 0.419 | neutral | N | 0.495484512 | None | None | N |
| I/M | 0.1398 | likely_benign | 0.1221 | benign | -0.744 | Destabilizing | 0.177 | N | 0.612 | neutral | N | 0.477352585 | None | None | N |
| I/N | 0.4756 | ambiguous | 0.4408 | ambiguous | -1.656 | Destabilizing | 0.303 | N | 0.692 | prob.delet. | N | 0.495545745 | None | None | N |
| I/P | 0.9433 | likely_pathogenic | 0.9438 | pathogenic | -1.312 | Destabilizing | 0.221 | N | 0.691 | prob.delet. | None | None | None | None | N |
| I/Q | 0.5667 | likely_pathogenic | 0.5286 | ambiguous | -1.727 | Destabilizing | 0.366 | N | 0.693 | prob.delet. | None | None | None | None | N |
| I/R | 0.5026 | ambiguous | 0.4922 | ambiguous | -1.131 | Destabilizing | 0.221 | N | 0.696 | prob.delet. | None | None | None | None | N |
| I/S | 0.3808 | ambiguous | 0.353 | ambiguous | -2.259 | Highly Destabilizing | 0.03 | N | 0.653 | prob.neutral | N | 0.494785276 | None | None | N |
| I/T | 0.2393 | likely_benign | 0.2138 | benign | -2.043 | Highly Destabilizing | 0.03 | N | 0.653 | prob.neutral | N | 0.517915867 | None | None | N |
| I/V | 0.0598 | likely_benign | 0.0523 | benign | -1.312 | Destabilizing | None | N | 0.135 | neutral | N | 0.404998581 | None | None | N |
| I/W | 0.9048 | likely_pathogenic | 0.8949 | pathogenic | -1.466 | Destabilizing | 0.869 | D | 0.732 | deleterious | None | None | None | None | N |
| I/Y | 0.6821 | likely_pathogenic | 0.6456 | pathogenic | -1.245 | Destabilizing | 0.366 | N | 0.649 | 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.