Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28288 | 85087;85088;85089 | chr2:178561270;178561269;178561268 | chr2:179425997;179425996;179425995 |
| N2AB | 26647 | 80164;80165;80166 | chr2:178561270;178561269;178561268 | chr2:179425997;179425996;179425995 |
| N2A | 25720 | 77383;77384;77385 | chr2:178561270;178561269;178561268 | chr2:179425997;179425996;179425995 |
| N2B | 19223 | 57892;57893;57894 | chr2:178561270;178561269;178561268 | chr2:179425997;179425996;179425995 |
| Novex-1 | 19348 | 58267;58268;58269 | chr2:178561270;178561269;178561268 | chr2:179425997;179425996;179425995 |
| Novex-2 | 19415 | 58468;58469;58470 | chr2:178561270;178561269;178561268 | chr2:179425997;179425996;179425995 |
| 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/L | None | None | 0.002 | N | 0.289 | 0.106 | 0.507510703362 | gnomAD-4.0.0 | 6.84213E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99446E-07 | 0 | 0 |
| I/N | None | None | 0.975 | N | 0.776 | 0.453 | 0.807978538823 | gnomAD-4.0.0 | 6.84225E-07 | None | None | None | None | N | None | 0 | 2.23614E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | None | None | 0.864 | N | 0.655 | 0.431 | 0.678712887374 | gnomAD-4.0.0 | 4.10535E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.7989E-06 | 2.31868E-05 | 3.31301E-05 |
| I/V | rs775883370  |
-1.433 | 0.141 | N | 0.412 | 0.069 | 0.417334834585 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.88E-06 | 0 |
| I/V | rs775883370 |
-1.433 | 0.141 | N | 0.412 | 0.069 | 0.417334834585 | gnomAD-4.0.0 | 8.89476E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.16928E-05 | 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 | 0.2977 | likely_benign | 0.3238 | benign | -2.3 | Highly Destabilizing | 0.707 | D | 0.629 | neutral | None | None | None | None | N |
| I/C | 0.6491 | likely_pathogenic | 0.6745 | pathogenic | -1.391 | Destabilizing | 0.995 | D | 0.672 | neutral | None | None | None | None | N |
| I/D | 0.8013 | likely_pathogenic | 0.7961 | pathogenic | -2.473 | Highly Destabilizing | 0.981 | D | 0.755 | deleterious | None | None | None | None | N |
| I/E | 0.7174 | likely_pathogenic | 0.678 | pathogenic | -2.286 | Highly Destabilizing | 0.945 | D | 0.747 | deleterious | None | None | None | None | N |
| I/F | 0.1634 | likely_benign | 0.1678 | benign | -1.384 | Destabilizing | 0.761 | D | 0.663 | neutral | N | 0.477027097 | None | None | N |
| I/G | 0.7289 | likely_pathogenic | 0.7506 | pathogenic | -2.792 | Highly Destabilizing | 0.945 | D | 0.73 | prob.delet. | None | None | None | None | N |
| I/H | 0.5005 | ambiguous | 0.4894 | ambiguous | -2.151 | Highly Destabilizing | 0.995 | D | 0.743 | deleterious | None | None | None | None | N |
| I/K | 0.5983 | likely_pathogenic | 0.5513 | ambiguous | -1.864 | Destabilizing | 0.945 | D | 0.729 | prob.delet. | None | None | None | None | N |
| I/L | 0.1063 | likely_benign | 0.124 | benign | -0.903 | Destabilizing | 0.002 | N | 0.289 | neutral | N | 0.464074176 | None | None | N |
| I/M | 0.089 | likely_benign | 0.0947 | benign | -0.675 | Destabilizing | 0.864 | D | 0.682 | prob.neutral | N | 0.496385573 | None | None | N |
| I/N | 0.3218 | likely_benign | 0.3193 | benign | -2.116 | Highly Destabilizing | 0.975 | D | 0.776 | deleterious | N | 0.470315147 | None | None | N |
| I/P | 0.9834 | likely_pathogenic | 0.9824 | pathogenic | -1.348 | Destabilizing | 0.981 | D | 0.775 | deleterious | None | None | None | None | N |
| I/Q | 0.522 | ambiguous | 0.4986 | ambiguous | -2.046 | Highly Destabilizing | 0.981 | D | 0.769 | deleterious | None | None | None | None | N |
| I/R | 0.4555 | ambiguous | 0.4128 | ambiguous | -1.44 | Destabilizing | 0.945 | D | 0.775 | deleterious | None | None | None | None | N |
| I/S | 0.2621 | likely_benign | 0.268 | benign | -2.767 | Highly Destabilizing | 0.928 | D | 0.639 | neutral | N | 0.478264411 | None | None | N |
| I/T | 0.1313 | likely_benign | 0.1423 | benign | -2.451 | Highly Destabilizing | 0.864 | D | 0.655 | neutral | N | 0.496218018 | None | None | N |
| I/V | 0.067 | likely_benign | 0.0721 | benign | -1.348 | Destabilizing | 0.141 | N | 0.412 | neutral | N | 0.470244925 | None | None | N |
| I/W | 0.7649 | likely_pathogenic | 0.765 | pathogenic | -1.766 | Destabilizing | 0.995 | D | 0.729 | prob.delet. | None | None | None | None | N |
| I/Y | 0.4904 | ambiguous | 0.484 | ambiguous | -1.454 | Destabilizing | 0.945 | D | 0.662 | 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.