Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31627 | 95104;95105;95106 | chr2:178546452;178546451;178546450 | chr2:179411179;179411178;179411177 |
| N2AB | 29986 | 90181;90182;90183 | chr2:178546452;178546451;178546450 | chr2:179411179;179411178;179411177 |
| N2A | 29059 | 87400;87401;87402 | chr2:178546452;178546451;178546450 | chr2:179411179;179411178;179411177 |
| N2B | 22562 | 67909;67910;67911 | chr2:178546452;178546451;178546450 | chr2:179411179;179411178;179411177 |
| Novex-1 | 22687 | 68284;68285;68286 | chr2:178546452;178546451;178546450 | chr2:179411179;179411178;179411177 |
| Novex-2 | 22754 | 68485;68486;68487 | chr2:178546452;178546451;178546450 | chr2:179411179;179411178;179411177 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/L | None | None | 0.58 | N | 0.41 | 0.197 | 0.552367828057 | gnomAD-4.0.0 | 1.59161E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85873E-06 | 0 | 0 |
| I/M | None | None | 0.991 | N | 0.491 | 0.44 | 0.603382761471 | gnomAD-4.0.0 | 1.36855E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.319E-05 | 0 |
| I/T | rs751714990  |
-1.557 | 0.939 | N | 0.518 | 0.565 | 0.748615457965 | gnomAD-2.1.1 | 2.02E-05 | None | None | None | None | I | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 3.58E-05 | 0 |
| I/T | rs751714990 |
-1.557 | 0.939 | N | 0.518 | 0.565 | 0.748615457965 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| I/T | rs751714990 |
-1.557 | 0.939 | N | 0.518 | 0.565 | 0.748615457965 | gnomAD-4.0.0 | 3.2227E-05 | None | None | None | None | I | None | 5.34074E-05 | 1.66722E-05 | None | 0 | 0 | None | 0 | 0 | 3.56015E-05 | 0 | 8.00641E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.7517 | likely_pathogenic | 0.786 | pathogenic | -1.93 | Destabilizing | 0.91 | D | 0.407 | neutral | None | None | None | None | I |
| I/C | 0.8758 | likely_pathogenic | 0.8931 | pathogenic | -1.295 | Destabilizing | 0.999 | D | 0.494 | neutral | None | None | None | None | I |
| I/D | 0.9902 | likely_pathogenic | 0.9918 | pathogenic | -1.316 | Destabilizing | 0.998 | D | 0.622 | neutral | None | None | None | None | I |
| I/E | 0.9568 | likely_pathogenic | 0.9638 | pathogenic | -1.263 | Destabilizing | 0.993 | D | 0.627 | neutral | None | None | None | None | I |
| I/F | 0.4391 | ambiguous | 0.4829 | ambiguous | -1.251 | Destabilizing | 0.982 | D | 0.516 | neutral | N | 0.507599381 | None | None | I |
| I/G | 0.9549 | likely_pathogenic | 0.9639 | pathogenic | -2.311 | Highly Destabilizing | 0.993 | D | 0.629 | neutral | None | None | None | None | I |
| I/H | 0.9439 | likely_pathogenic | 0.9555 | pathogenic | -1.503 | Destabilizing | 0.999 | D | 0.615 | neutral | None | None | None | None | I |
| I/K | 0.9081 | likely_pathogenic | 0.9203 | pathogenic | -1.366 | Destabilizing | 0.993 | D | 0.629 | neutral | None | None | None | None | I |
| I/L | 0.1834 | likely_benign | 0.2031 | benign | -0.927 | Destabilizing | 0.58 | D | 0.41 | neutral | N | 0.500581766 | None | None | I |
| I/M | 0.2429 | likely_benign | 0.2714 | benign | -0.788 | Destabilizing | 0.991 | D | 0.491 | neutral | N | 0.507599381 | None | None | I |
| I/N | 0.9161 | likely_pathogenic | 0.9277 | pathogenic | -1.259 | Destabilizing | 0.997 | D | 0.631 | neutral | N | 0.519716155 | None | None | I |
| I/P | 0.9845 | likely_pathogenic | 0.9869 | pathogenic | -1.232 | Destabilizing | 0.998 | D | 0.626 | neutral | None | None | None | None | I |
| I/Q | 0.9124 | likely_pathogenic | 0.9267 | pathogenic | -1.375 | Destabilizing | 0.998 | D | 0.635 | neutral | None | None | None | None | I |
| I/R | 0.8703 | likely_pathogenic | 0.8913 | pathogenic | -0.824 | Destabilizing | 0.993 | D | 0.635 | neutral | None | None | None | None | I |
| I/S | 0.8655 | likely_pathogenic | 0.8849 | pathogenic | -1.961 | Destabilizing | 0.991 | D | 0.568 | neutral | N | 0.496078491 | None | None | I |
| I/T | 0.7488 | likely_pathogenic | 0.7871 | pathogenic | -1.785 | Destabilizing | 0.939 | D | 0.518 | neutral | N | 0.499837473 | None | None | I |
| I/V | 0.0742 | likely_benign | 0.0793 | benign | -1.232 | Destabilizing | 0.02 | N | 0.222 | neutral | N | 0.3915045 | None | None | I |
| I/W | 0.9682 | likely_pathogenic | 0.975 | pathogenic | -1.354 | Destabilizing | 0.999 | D | 0.595 | neutral | None | None | None | None | I |
| I/Y | 0.8834 | likely_pathogenic | 0.9016 | pathogenic | -1.131 | Destabilizing | 0.993 | D | 0.495 | neutral | None | None | 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.