Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 5308 | 16147;16148;16149 | chr2:178733371;178733370;178733369 | chr2:179598098;179598097;179598096 |
| N2AB | 4991 | 15196;15197;15198 | chr2:178733371;178733370;178733369 | chr2:179598098;179598097;179598096 |
| N2A | 4064 | 12415;12416;12417 | chr2:178733371;178733370;178733369 | chr2:179598098;179598097;179598096 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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/Q | rs146847928  |
-0.482 | 0.993 | N | 0.497 | 0.331 | None | gnomAD-2.1.1 | 5.71E-05 | None | None | None | None | N | None | 1.65399E-04 | 0 | None | 0 | 3.07724E-04 | None | 6.54E-05 | None | 4E-05 | 1.56E-05 | 1.40449E-04 |
| R/Q | rs146847928 |
-0.482 | 0.993 | N | 0.497 | 0.331 | None | gnomAD-3.1.2 | 4.6E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 1.9253E-04 | None | 9.42E-05 | 3.16456E-03 | 1.47E-05 | 0 | 4.78927E-04 |
| R/Q | rs146847928 |
-0.482 | 0.993 | N | 0.497 | 0.331 | None | 1000 genomes | 3.99361E-04 | None | None | None | None | N | None | 1.5E-03 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/Q | rs146847928 |
-0.482 | 0.993 | N | 0.497 | 0.331 | None | gnomAD-4.0.0 | 4.15185E-05 | None | None | None | None | N | None | 7.99872E-05 | 0 | None | 0 | 1.33738E-04 | None | 1.56216E-05 | 1.65071E-04 | 3.64479E-05 | 8.78542E-05 | 3.20154E-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 | 0.7332 | likely_pathogenic | 0.776 | pathogenic | -0.329 | Destabilizing | 0.931 | D | 0.475 | neutral | None | None | None | None | N |
| R/C | 0.4171 | ambiguous | 0.4463 | ambiguous | -0.396 | Destabilizing | 1.0 | D | 0.643 | neutral | None | None | None | None | N |
| R/D | 0.8941 | likely_pathogenic | 0.9149 | pathogenic | 0.101 | Stabilizing | 0.996 | D | 0.484 | neutral | None | None | None | None | N |
| R/E | 0.6734 | likely_pathogenic | 0.727 | pathogenic | 0.211 | Stabilizing | 0.97 | D | 0.451 | neutral | None | None | None | None | N |
| R/F | 0.8349 | likely_pathogenic | 0.8542 | pathogenic | -0.343 | Destabilizing | 0.999 | D | 0.615 | neutral | None | None | None | None | N |
| R/G | 0.6021 | likely_pathogenic | 0.6518 | pathogenic | -0.596 | Destabilizing | 0.992 | D | 0.484 | neutral | N | 0.515160847 | None | None | N |
| R/H | 0.1883 | likely_benign | 0.2132 | benign | -1.061 | Destabilizing | 0.999 | D | 0.479 | neutral | None | None | None | None | N |
| R/I | 0.517 | ambiguous | 0.553 | ambiguous | 0.362 | Stabilizing | 0.999 | D | 0.609 | neutral | None | None | None | None | N |
| R/K | 0.1873 | likely_benign | 0.1996 | benign | -0.254 | Destabilizing | 0.155 | N | 0.121 | neutral | None | None | None | None | N |
| R/L | 0.5086 | ambiguous | 0.555 | ambiguous | 0.362 | Stabilizing | 0.992 | D | 0.484 | neutral | N | 0.513210539 | None | None | N |
| R/M | 0.5495 | ambiguous | 0.5964 | pathogenic | -0.101 | Destabilizing | 1.0 | D | 0.549 | neutral | None | None | None | None | N |
| R/N | 0.8267 | likely_pathogenic | 0.854 | pathogenic | 0.057 | Stabilizing | 0.985 | D | 0.459 | neutral | None | None | None | None | N |
| R/P | 0.9664 | likely_pathogenic | 0.9652 | pathogenic | 0.154 | Stabilizing | 0.999 | D | 0.548 | neutral | D | 0.57697762 | None | None | N |
| R/Q | 0.1857 | likely_benign | 0.2194 | benign | -0.043 | Destabilizing | 0.993 | D | 0.497 | neutral | N | 0.455261573 | None | None | N |
| R/S | 0.771 | likely_pathogenic | 0.8066 | pathogenic | -0.529 | Destabilizing | 0.97 | D | 0.465 | neutral | None | None | None | None | N |
| R/T | 0.5705 | likely_pathogenic | 0.6192 | pathogenic | -0.244 | Destabilizing | 0.985 | D | 0.491 | neutral | None | None | None | None | N |
| R/V | 0.6102 | likely_pathogenic | 0.651 | pathogenic | 0.154 | Stabilizing | 0.996 | D | 0.508 | neutral | None | None | None | None | N |
| R/W | 0.3788 | ambiguous | 0.4337 | ambiguous | -0.208 | Destabilizing | 1.0 | D | 0.678 | prob.neutral | None | None | None | None | N |
| R/Y | 0.6709 | likely_pathogenic | 0.7117 | pathogenic | 0.157 | Stabilizing | 0.999 | D | 0.595 | 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.