Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 8586 | 25981;25982;25983 | chr2:178715658;178715657;178715656 | chr2:179580385;179580384;179580383 |
| N2AB | 8269 | 25030;25031;25032 | chr2:178715658;178715657;178715656 | chr2:179580385;179580384;179580383 |
| N2A | 7342 | 22249;22250;22251 | chr2:178715658;178715657;178715656 | chr2:179580385;179580384;179580383 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/N | rs1199035064  |
-0.546 | None | N | 0.091 | 0.086 | 0.12205267543 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 6.48E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/N | rs1199035064 |
-0.546 | None | N | 0.091 | 0.086 | 0.12205267543 | gnomAD-4.0.0 | 3.42209E-06 | None | None | None | None | N | None | 1.19581E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65711E-05 |
| D/V | rs1484446680 |
-0.067 | 0.013 | N | 0.479 | 0.215 | 0.322230723748 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.28E-05 | None | 0 | 0 | 0 |
| D/V | rs1484446680 |
-0.067 | 0.013 | N | 0.479 | 0.215 | 0.322230723748 | gnomAD-4.0.0 | 1.5924E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43386E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1996 | likely_benign | 0.2433 | benign | -0.578 | Destabilizing | 0.004 | N | 0.343 | neutral | N | 0.477335677 | None | None | N |
| D/C | 0.6454 | likely_pathogenic | 0.6947 | pathogenic | -0.108 | Destabilizing | 0.403 | N | 0.428 | neutral | None | None | None | None | N |
| D/E | 0.2104 | likely_benign | 0.2337 | benign | -0.501 | Destabilizing | None | N | 0.127 | neutral | N | 0.49702052 | None | None | N |
| D/F | 0.6498 | likely_pathogenic | 0.7078 | pathogenic | -0.408 | Destabilizing | 0.423 | N | 0.449 | neutral | None | None | None | None | N |
| D/G | 0.0978 | likely_benign | 0.1162 | benign | -0.836 | Destabilizing | None | N | 0.126 | neutral | N | 0.472199434 | None | None | N |
| D/H | 0.3035 | likely_benign | 0.3625 | ambiguous | -0.525 | Destabilizing | None | N | 0.159 | neutral | N | 0.500555267 | None | None | N |
| D/I | 0.6249 | likely_pathogenic | 0.6794 | pathogenic | 0.074 | Stabilizing | 0.423 | N | 0.477 | neutral | None | None | None | None | N |
| D/K | 0.413 | ambiguous | 0.4679 | ambiguous | -0.111 | Destabilizing | 0.021 | N | 0.343 | neutral | None | None | None | None | N |
| D/L | 0.4705 | ambiguous | 0.541 | ambiguous | 0.074 | Stabilizing | 0.093 | N | 0.487 | neutral | None | None | None | None | N |
| D/M | 0.6517 | likely_pathogenic | 0.7014 | pathogenic | 0.426 | Stabilizing | 0.455 | N | 0.427 | neutral | None | None | None | None | N |
| D/N | 0.0704 | likely_benign | 0.0771 | benign | -0.426 | Destabilizing | None | N | 0.091 | neutral | N | 0.394274581 | None | None | N |
| D/P | 0.9257 | likely_pathogenic | 0.9454 | pathogenic | -0.12 | Destabilizing | 0.004 | N | 0.439 | neutral | None | None | None | None | N |
| D/Q | 0.3675 | ambiguous | 0.4266 | ambiguous | -0.358 | Destabilizing | 0.001 | N | 0.15 | neutral | None | None | None | None | N |
| D/R | 0.4155 | ambiguous | 0.4825 | ambiguous | 0.05 | Stabilizing | 0.049 | N | 0.477 | neutral | None | None | None | None | N |
| D/S | 0.1395 | likely_benign | 0.1613 | benign | -0.582 | Destabilizing | 0.006 | N | 0.186 | neutral | None | None | None | None | N |
| D/T | 0.4001 | ambiguous | 0.4586 | ambiguous | -0.38 | Destabilizing | 0.005 | N | 0.347 | neutral | None | None | None | None | N |
| D/V | 0.394 | ambiguous | 0.4509 | ambiguous | -0.12 | Destabilizing | 0.013 | N | 0.479 | neutral | N | 0.489452451 | None | None | N |
| D/W | 0.8452 | likely_pathogenic | 0.8819 | pathogenic | -0.23 | Destabilizing | 0.894 | D | 0.436 | neutral | None | None | None | None | N |
| D/Y | 0.2235 | likely_benign | 0.2654 | benign | -0.177 | Destabilizing | 0.214 | N | 0.49 | neutral | N | 0.494225391 | 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.