Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25076 | 75451;75452;75453 | chr2:178570906;178570905;178570904 | chr2:179435633;179435632;179435631 |
| N2AB | 23435 | 70528;70529;70530 | chr2:178570906;178570905;178570904 | chr2:179435633;179435632;179435631 |
| N2A | 22508 | 67747;67748;67749 | chr2:178570906;178570905;178570904 | chr2:179435633;179435632;179435631 |
| N2B | 16011 | 48256;48257;48258 | chr2:178570906;178570905;178570904 | chr2:179435633;179435632;179435631 |
| Novex-1 | 16136 | 48631;48632;48633 | chr2:178570906;178570905;178570904 | chr2:179435633;179435632;179435631 |
| Novex-2 | 16203 | 48832;48833;48834 | chr2:178570906;178570905;178570904 | chr2:179435633;179435632;179435631 |
| 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/S | rs758951524  |
-0.978 | 0.491 | N | 0.36 | 0.175 | 0.17948927462 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.65837E-04 |
| R/S | rs758951524 |
-0.978 | 0.491 | N | 0.36 | 0.175 | 0.17948927462 | gnomAD-4.0.0 | 3.18342E-06 | None | None | None | None | N | None | 0 | 2.28666E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.02499E-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 | 0.4218 | ambiguous | 0.3887 | ambiguous | -0.828 | Destabilizing | 0.345 | N | 0.365 | neutral | None | None | None | None | N |
| R/C | 0.1865 | likely_benign | 0.1646 | benign | -0.803 | Destabilizing | 0.991 | D | 0.351 | neutral | None | None | None | None | N |
| R/D | 0.7555 | likely_pathogenic | 0.7227 | pathogenic | 0.02 | Stabilizing | 0.39 | N | 0.389 | neutral | None | None | None | None | N |
| R/E | 0.4101 | ambiguous | 0.3655 | ambiguous | 0.162 | Stabilizing | 0.002 | N | 0.101 | neutral | None | None | None | None | N |
| R/F | 0.6789 | likely_pathogenic | 0.6408 | pathogenic | -0.544 | Destabilizing | 0.901 | D | 0.373 | neutral | None | None | None | None | N |
| R/G | 0.3649 | ambiguous | 0.3157 | benign | -1.153 | Destabilizing | 0.491 | N | 0.383 | neutral | N | 0.493468501 | None | None | N |
| R/H | 0.1439 | likely_benign | 0.1272 | benign | -1.391 | Destabilizing | 0.901 | D | 0.413 | neutral | None | None | None | None | N |
| R/I | 0.3189 | likely_benign | 0.2792 | benign | 0.052 | Stabilizing | 0.005 | N | 0.251 | neutral | N | 0.482232787 | None | None | N |
| R/K | 0.1416 | likely_benign | 0.1291 | benign | -0.774 | Destabilizing | 0.166 | N | 0.354 | neutral | N | 0.405809444 | None | None | N |
| R/L | 0.2996 | likely_benign | 0.2655 | benign | 0.052 | Stabilizing | 0.209 | N | 0.359 | neutral | None | None | None | None | N |
| R/M | 0.3504 | ambiguous | 0.3064 | benign | -0.384 | Destabilizing | 0.901 | D | 0.377 | neutral | None | None | None | None | N |
| R/N | 0.639 | likely_pathogenic | 0.6034 | pathogenic | -0.331 | Destabilizing | 0.561 | D | 0.377 | neutral | None | None | None | None | N |
| R/P | 0.7009 | likely_pathogenic | 0.6722 | pathogenic | -0.221 | Destabilizing | 0.901 | D | 0.362 | neutral | None | None | None | None | N |
| R/Q | 0.1104 | likely_benign | 0.1012 | benign | -0.436 | Destabilizing | 0.047 | N | 0.173 | neutral | None | None | None | None | N |
| R/S | 0.4885 | ambiguous | 0.4387 | ambiguous | -1.115 | Destabilizing | 0.491 | N | 0.36 | neutral | N | 0.448157499 | None | None | N |
| R/T | 0.2471 | likely_benign | 0.2175 | benign | -0.782 | Destabilizing | 0.491 | N | 0.369 | neutral | N | 0.431283892 | None | None | N |
| R/V | 0.3919 | ambiguous | 0.3595 | ambiguous | -0.221 | Destabilizing | 0.209 | N | 0.373 | neutral | None | None | None | None | N |
| R/W | 0.2835 | likely_benign | 0.2566 | benign | -0.182 | Destabilizing | 0.991 | D | 0.381 | neutral | None | None | None | None | N |
| R/Y | 0.4769 | ambiguous | 0.4477 | ambiguous | 0.084 | Stabilizing | 0.965 | D | 0.365 | 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.