Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31417 | 94474;94475;94476 | chr2:178547276;178547275;178547274 | chr2:179412003;179412002;179412001 |
| N2AB | 29776 | 89551;89552;89553 | chr2:178547276;178547275;178547274 | chr2:179412003;179412002;179412001 |
| N2A | 28849 | 86770;86771;86772 | chr2:178547276;178547275;178547274 | chr2:179412003;179412002;179412001 |
| N2B | 22352 | 67279;67280;67281 | chr2:178547276;178547275;178547274 | chr2:179412003;179412002;179412001 |
| Novex-1 | 22477 | 67654;67655;67656 | chr2:178547276;178547275;178547274 | chr2:179412003;179412002;179412001 |
| Novex-2 | 22544 | 67855;67856;67857 | chr2:178547276;178547275;178547274 | chr2:179412003;179412002;179412001 |
| 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 | rs878947167  |
-1.335 | 0.834 | N | 0.585 | 0.282 | None | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.66279E-04 |
| V/A | rs878947167 |
-1.335 | 0.834 | N | 0.585 | 0.282 | None | gnomAD-4.0.0 | 5.47692E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.19996E-06 | 0 | 0 |
| V/I | rs1188866872 |
None | 0.016 | N | 0.288 | 0.106 | 0.413761986042 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| V/I | rs1188866872 |
None | 0.016 | N | 0.288 | 0.106 | 0.413761986042 | gnomAD-4.0.0 | 6.57333E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47029E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.4484 | ambiguous | 0.4535 | ambiguous | -1.823 | Destabilizing | 0.834 | D | 0.585 | neutral | N | 0.49972247 | None | None | N |
| V/C | 0.8465 | likely_pathogenic | 0.8564 | pathogenic | -1.161 | Destabilizing | 0.998 | D | 0.837 | deleterious | None | None | None | None | N |
| V/D | 0.9593 | likely_pathogenic | 0.9601 | pathogenic | -2.035 | Highly Destabilizing | 0.973 | D | 0.873 | deleterious | N | 0.49354578 | None | None | N |
| V/E | 0.9356 | likely_pathogenic | 0.9384 | pathogenic | -1.863 | Destabilizing | 0.979 | D | 0.867 | deleterious | None | None | None | None | N |
| V/F | 0.6859 | likely_pathogenic | 0.7062 | pathogenic | -1.09 | Destabilizing | 0.946 | D | 0.873 | deleterious | N | 0.484614875 | None | None | N |
| V/G | 0.6541 | likely_pathogenic | 0.6642 | pathogenic | -2.315 | Highly Destabilizing | 0.973 | D | 0.855 | deleterious | N | 0.498127682 | None | None | N |
| V/H | 0.9778 | likely_pathogenic | 0.9787 | pathogenic | -1.969 | Destabilizing | 0.998 | D | 0.877 | deleterious | None | None | None | None | N |
| V/I | 0.0764 | likely_benign | 0.0806 | benign | -0.481 | Destabilizing | 0.016 | N | 0.288 | neutral | N | 0.455934407 | None | None | N |
| V/K | 0.9608 | likely_pathogenic | 0.9614 | pathogenic | -1.536 | Destabilizing | 0.979 | D | 0.867 | deleterious | None | None | None | None | N |
| V/L | 0.4953 | ambiguous | 0.528 | ambiguous | -0.481 | Destabilizing | 0.263 | N | 0.471 | neutral | N | 0.508363383 | None | None | N |
| V/M | 0.4364 | ambiguous | 0.4797 | ambiguous | -0.366 | Destabilizing | 0.959 | D | 0.791 | deleterious | None | None | None | None | N |
| V/N | 0.8467 | likely_pathogenic | 0.8478 | pathogenic | -1.679 | Destabilizing | 0.993 | D | 0.882 | deleterious | None | None | None | None | N |
| V/P | 0.6785 | likely_pathogenic | 0.6774 | pathogenic | -0.898 | Destabilizing | 0.993 | D | 0.885 | deleterious | None | None | None | None | N |
| V/Q | 0.9433 | likely_pathogenic | 0.9419 | pathogenic | -1.594 | Destabilizing | 0.993 | D | 0.889 | deleterious | None | None | None | None | N |
| V/R | 0.9454 | likely_pathogenic | 0.9448 | pathogenic | -1.287 | Destabilizing | 0.979 | D | 0.88 | deleterious | None | None | None | None | N |
| V/S | 0.711 | likely_pathogenic | 0.7073 | pathogenic | -2.3 | Highly Destabilizing | 0.979 | D | 0.858 | deleterious | None | None | None | None | N |
| V/T | 0.5356 | ambiguous | 0.513 | ambiguous | -1.99 | Destabilizing | 0.87 | D | 0.719 | prob.delet. | None | None | None | None | N |
| V/W | 0.9854 | likely_pathogenic | 0.9853 | pathogenic | -1.546 | Destabilizing | 0.998 | D | 0.841 | deleterious | None | None | None | None | N |
| V/Y | 0.9338 | likely_pathogenic | 0.9381 | pathogenic | -1.149 | Destabilizing | 0.979 | D | 0.884 | 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.