Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20717 | 62374;62375;62376 | chr2:178589576;178589575;178589574 | chr2:179454303;179454302;179454301 |
| N2AB | 19076 | 57451;57452;57453 | chr2:178589576;178589575;178589574 | chr2:179454303;179454302;179454301 |
| N2A | 18149 | 54670;54671;54672 | chr2:178589576;178589575;178589574 | chr2:179454303;179454302;179454301 |
| N2B | 11652 | 35179;35180;35181 | chr2:178589576;178589575;178589574 | chr2:179454303;179454302;179454301 |
| Novex-1 | 11777 | 35554;35555;35556 | chr2:178589576;178589575;178589574 | chr2:179454303;179454302;179454301 |
| Novex-2 | 11844 | 35755;35756;35757 | chr2:178589576;178589575;178589574 | chr2:179454303;179454302;179454301 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/G | rs75458912  |
-0.95 | 0.98 | N | 0.609 | 0.329 | None | gnomAD-2.1.1 | 2.57955E-04 | None | None | None | None | N | None | 4.13E-05 | 5.67E-05 | None | 0 | 3.50479E-03 | None | 0 | None | 0 | 7.86E-06 | 0 |
| R/G | rs75458912 |
-0.95 | 0.98 | N | 0.609 | 0.329 | None | gnomAD-3.1.2 | 8.55E-05 | None | None | None | None | N | None | 2.41E-05 | 6.56E-05 | 0 | 0 | 2.13178E-03 | None | 0 | 0 | 0 | 0 | 0 |
| R/G | rs75458912 |
-0.95 | 0.98 | N | 0.609 | 0.329 | None | 1000 genomes | 3.99361E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| R/G | rs75458912 |
-0.95 | 0.98 | N | 0.609 | 0.329 | None | gnomAD-4.0.0 | 1.03506E-04 | None | None | None | None | N | None | 1.3328E-05 | 5.0025E-05 | None | 0 | 3.44103E-03 | None | 0 | 1.65235E-04 | 4.23867E-06 | 0 | 4.80231E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.8064 | likely_pathogenic | 0.7646 | pathogenic | -0.661 | Destabilizing | 0.931 | D | 0.559 | neutral | None | None | None | None | N |
| R/C | 0.5596 | ambiguous | 0.5476 | ambiguous | -0.609 | Destabilizing | 1.0 | D | 0.74 | deleterious | None | None | None | None | N |
| R/D | 0.9356 | likely_pathogenic | 0.9217 | pathogenic | -0.281 | Destabilizing | 0.996 | D | 0.645 | neutral | None | None | None | None | N |
| R/E | 0.7279 | likely_pathogenic | 0.7143 | pathogenic | -0.093 | Destabilizing | 0.97 | D | 0.489 | neutral | None | None | None | None | N |
| R/F | 0.8892 | likely_pathogenic | 0.8707 | pathogenic | -0.013 | Destabilizing | 0.999 | D | 0.739 | prob.delet. | None | None | None | None | N |
| R/G | 0.8051 | likely_pathogenic | 0.7661 | pathogenic | -1.04 | Destabilizing | 0.98 | D | 0.609 | neutral | N | 0.517153437 | None | None | N |
| R/H | 0.3623 | ambiguous | 0.3475 | ambiguous | -1.372 | Destabilizing | 0.999 | D | 0.593 | neutral | None | None | None | None | N |
| R/I | 0.6013 | likely_pathogenic | 0.5381 | ambiguous | 0.39 | Stabilizing | 0.998 | D | 0.735 | prob.delet. | N | 0.476653609 | None | None | N |
| R/K | 0.2042 | likely_benign | 0.2391 | benign | -0.741 | Destabilizing | 0.122 | N | 0.138 | neutral | N | 0.403868004 | None | None | N |
| R/L | 0.5786 | likely_pathogenic | 0.5245 | ambiguous | 0.39 | Stabilizing | 0.985 | D | 0.609 | neutral | None | None | None | None | N |
| R/M | 0.6363 | likely_pathogenic | 0.5834 | pathogenic | -0.169 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | N |
| R/N | 0.9026 | likely_pathogenic | 0.8818 | pathogenic | -0.553 | Destabilizing | 0.985 | D | 0.539 | neutral | None | None | None | None | N |
| R/P | 0.7576 | likely_pathogenic | 0.6982 | pathogenic | 0.06 | Stabilizing | 0.999 | D | 0.688 | prob.neutral | None | None | None | None | N |
| R/Q | 0.3205 | likely_benign | 0.3166 | benign | -0.42 | Destabilizing | 0.97 | D | 0.56 | neutral | None | None | None | None | N |
| R/S | 0.9181 | likely_pathogenic | 0.8933 | pathogenic | -1.114 | Destabilizing | 0.961 | D | 0.571 | neutral | N | 0.504376141 | None | None | N |
| R/T | 0.7313 | likely_pathogenic | 0.6669 | pathogenic | -0.722 | Destabilizing | 0.98 | D | 0.617 | neutral | N | 0.470532926 | None | None | N |
| R/V | 0.6592 | likely_pathogenic | 0.6199 | pathogenic | 0.06 | Stabilizing | 0.996 | D | 0.652 | neutral | None | None | None | None | N |
| R/W | 0.5422 | ambiguous | 0.5227 | ambiguous | 0.276 | Stabilizing | 1.0 | D | 0.748 | deleterious | None | None | None | None | N |
| R/Y | 0.7873 | likely_pathogenic | 0.784 | pathogenic | 0.514 | Stabilizing | 0.999 | D | 0.733 | prob.delet. | 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.