Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19207 | 57844;57845;57846 | chr2:178595735;178595734;178595733 | chr2:179460462;179460461;179460460 |
| N2AB | 17566 | 52921;52922;52923 | chr2:178595735;178595734;178595733 | chr2:179460462;179460461;179460460 |
| N2A | 16639 | 50140;50141;50142 | chr2:178595735;178595734;178595733 | chr2:179460462;179460461;179460460 |
| N2B | 10142 | 30649;30650;30651 | chr2:178595735;178595734;178595733 | chr2:179460462;179460461;179460460 |
| Novex-1 | 10267 | 31024;31025;31026 | chr2:178595735;178595734;178595733 | chr2:179460462;179460461;179460460 |
| Novex-2 | 10334 | 31225;31226;31227 | chr2:178595735;178595734;178595733 | chr2:179460462;179460461;179460460 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/C | rs2051384370  |
None | 0.883 | N | 0.669 | 0.291 | 0.395745362164 | gnomAD-4.0.0 | 1.60229E-06 | None | None | None | None | I | None | 0 | 2.30979E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/P | None | None | 0.667 | N | 0.659 | 0.221 | 0.190952846119 | gnomAD-4.0.0 | 1.60208E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.87221E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0781 | likely_benign | 0.0869 | benign | -0.608 | Destabilizing | 0.055 | N | 0.481 | neutral | N | 0.401710346 | None | None | I |
| S/C | 0.1 | likely_benign | 0.1213 | benign | -0.474 | Destabilizing | 0.883 | D | 0.669 | neutral | N | 0.490025551 | None | None | I |
| S/D | 0.6024 | likely_pathogenic | 0.6487 | pathogenic | -0.097 | Destabilizing | 0.272 | N | 0.488 | neutral | None | None | None | None | I |
| S/E | 0.6344 | likely_pathogenic | 0.7065 | pathogenic | -0.018 | Destabilizing | 0.272 | N | 0.486 | neutral | None | None | None | None | I |
| S/F | 0.1869 | likely_benign | 0.2485 | benign | -0.832 | Destabilizing | 0.002 | N | 0.423 | neutral | N | 0.460396077 | None | None | I |
| S/G | 0.1247 | likely_benign | 0.1327 | benign | -0.894 | Destabilizing | 0.272 | N | 0.473 | neutral | None | None | None | None | I |
| S/H | 0.3626 | ambiguous | 0.4345 | ambiguous | -1.146 | Destabilizing | 0.968 | D | 0.676 | prob.neutral | None | None | None | None | I |
| S/I | 0.1543 | likely_benign | 0.1872 | benign | 0.064 | Stabilizing | 0.396 | N | 0.678 | prob.neutral | None | None | None | None | I |
| S/K | 0.7751 | likely_pathogenic | 0.8475 | pathogenic | -0.293 | Destabilizing | 0.272 | N | 0.485 | neutral | None | None | None | None | I |
| S/L | 0.0833 | likely_benign | 0.1028 | benign | 0.064 | Stabilizing | 0.157 | N | 0.595 | neutral | None | None | None | None | I |
| S/M | 0.1672 | likely_benign | 0.2035 | benign | -0.059 | Destabilizing | 0.909 | D | 0.676 | prob.neutral | None | None | None | None | I |
| S/N | 0.1837 | likely_benign | 0.2059 | benign | -0.579 | Destabilizing | 0.272 | N | 0.507 | neutral | None | None | None | None | I |
| S/P | 0.0831 | likely_benign | 0.0999 | benign | -0.126 | Destabilizing | 0.667 | D | 0.659 | neutral | N | 0.338984232 | None | None | I |
| S/Q | 0.497 | ambiguous | 0.5733 | pathogenic | -0.488 | Destabilizing | 0.726 | D | 0.537 | neutral | None | None | None | None | I |
| S/R | 0.7165 | likely_pathogenic | 0.8003 | pathogenic | -0.364 | Destabilizing | 0.567 | D | 0.66 | neutral | None | None | None | None | I |
| S/T | 0.0872 | likely_benign | 0.1029 | benign | -0.506 | Destabilizing | None | N | 0.201 | neutral | N | 0.459182569 | None | None | I |
| S/V | 0.1651 | likely_benign | 0.1967 | benign | -0.126 | Destabilizing | 0.157 | N | 0.616 | neutral | None | None | None | None | I |
| S/W | 0.3534 | ambiguous | 0.4274 | ambiguous | -0.946 | Destabilizing | 0.968 | D | 0.764 | deleterious | None | None | None | None | I |
| S/Y | 0.2042 | likely_benign | 0.2593 | benign | -0.563 | Destabilizing | 0.331 | N | 0.713 | prob.delet. | N | 0.489852193 | None | None | I |
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.