Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19391 | 58396;58397;58398 | chr2:178594222;178594221;178594220 | chr2:179458949;179458948;179458947 |
| N2AB | 17750 | 53473;53474;53475 | chr2:178594222;178594221;178594220 | chr2:179458949;179458948;179458947 |
| N2A | 16823 | 50692;50693;50694 | chr2:178594222;178594221;178594220 | chr2:179458949;179458948;179458947 |
| N2B | 10326 | 31201;31202;31203 | chr2:178594222;178594221;178594220 | chr2:179458949;179458948;179458947 |
| Novex-1 | 10451 | 31576;31577;31578 | chr2:178594222;178594221;178594220 | chr2:179458949;179458948;179458947 |
| Novex-2 | 10518 | 31777;31778;31779 | chr2:178594222;178594221;178594220 | chr2:179458949;179458948;179458947 |
| 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 | rs377633051  |
-0.117 | 0.447 | N | 0.239 | 0.219 | None | gnomAD-2.1.1 | 4.66E-05 | None | None | None | None | I | None | 4.54884E-04 | 5.69E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/N | rs377633051 |
-0.117 | 0.447 | N | 0.239 | 0.219 | None | gnomAD-3.1.2 | 9.21E-05 | None | None | None | None | I | None | 3.37985E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/N | rs377633051 |
-0.117 | 0.447 | N | 0.239 | 0.219 | None | gnomAD-4.0.0 | 1.55E-05 | None | None | None | None | I | None | 2.40481E-04 | 3.34079E-05 | None | 3.37906E-05 | 0 | None | 0 | 0 | 3.39105E-06 | 0 | 0 |
| D/Y | None | None | 0.996 | N | 0.578 | 0.381 | 0.726185039024 | gnomAD-4.0.0 | 6.84507E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99614E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.3803 | ambiguous | 0.3719 | ambiguous | -0.126 | Destabilizing | 0.698 | D | 0.455 | neutral | N | 0.487677338 | None | None | I |
| D/C | 0.8519 | likely_pathogenic | 0.8475 | pathogenic | -0.214 | Destabilizing | 0.998 | D | 0.611 | neutral | None | None | None | None | I |
| D/E | 0.3474 | ambiguous | 0.3393 | benign | -0.326 | Destabilizing | 0.058 | N | 0.253 | neutral | N | 0.492247498 | None | None | I |
| D/F | 0.8436 | likely_pathogenic | 0.8344 | pathogenic | -0.085 | Destabilizing | 0.978 | D | 0.579 | neutral | None | None | None | None | I |
| D/G | 0.4139 | ambiguous | 0.3869 | ambiguous | -0.259 | Destabilizing | 0.698 | D | 0.461 | neutral | N | 0.489451765 | None | None | I |
| D/H | 0.5671 | likely_pathogenic | 0.5621 | ambiguous | 0.473 | Stabilizing | 0.997 | D | 0.485 | neutral | N | 0.490212234 | None | None | I |
| D/I | 0.6353 | likely_pathogenic | 0.6539 | pathogenic | 0.168 | Stabilizing | 0.978 | D | 0.58 | neutral | None | None | None | None | I |
| D/K | 0.7309 | likely_pathogenic | 0.7452 | pathogenic | 0.388 | Stabilizing | 0.86 | D | 0.463 | neutral | None | None | None | None | I |
| D/L | 0.6335 | likely_pathogenic | 0.6374 | pathogenic | 0.168 | Stabilizing | 0.956 | D | 0.573 | neutral | None | None | None | None | I |
| D/M | 0.8432 | likely_pathogenic | 0.8497 | pathogenic | 0.004 | Stabilizing | 0.998 | D | 0.593 | neutral | None | None | None | None | I |
| D/N | 0.2094 | likely_benign | 0.2599 | benign | 0.013 | Stabilizing | 0.447 | N | 0.239 | neutral | N | 0.488944786 | None | None | I |
| D/P | 0.8577 | likely_pathogenic | 0.8651 | pathogenic | 0.089 | Stabilizing | 0.978 | D | 0.483 | neutral | None | None | None | None | I |
| D/Q | 0.619 | likely_pathogenic | 0.6278 | pathogenic | 0.041 | Stabilizing | 0.956 | D | 0.477 | neutral | None | None | None | None | I |
| D/R | 0.7286 | likely_pathogenic | 0.7311 | pathogenic | 0.642 | Stabilizing | 0.956 | D | 0.531 | neutral | None | None | None | None | I |
| D/S | 0.2855 | likely_benign | 0.2814 | benign | -0.048 | Destabilizing | 0.16 | N | 0.25 | neutral | None | None | None | None | I |
| D/T | 0.4907 | ambiguous | 0.4955 | ambiguous | 0.069 | Stabilizing | 0.754 | D | 0.463 | neutral | None | None | None | None | I |
| D/V | 0.422 | ambiguous | 0.437 | ambiguous | 0.089 | Stabilizing | 0.942 | D | 0.577 | neutral | N | 0.488944786 | None | None | I |
| D/W | 0.9608 | likely_pathogenic | 0.9602 | pathogenic | 0.014 | Stabilizing | 0.998 | D | 0.627 | neutral | None | None | None | None | I |
| D/Y | 0.4921 | ambiguous | 0.482 | ambiguous | 0.149 | Stabilizing | 0.996 | D | 0.578 | neutral | N | 0.490465723 | 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.