Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 6041 | 18346;18347;18348 | chr2:178730279;178730278;178730277 | chr2:179595006;179595005;179595004 |
| N2AB | 5724 | 17395;17396;17397 | chr2:178730279;178730278;178730277 | chr2:179595006;179595005;179595004 |
| N2A | 4797 | 14614;14615;14616 | chr2:178730279;178730278;178730277 | chr2:179595006;179595005;179595004 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/K | None | None | 0.028 | N | 0.421 | 0.42 | 0.555712064712 | gnomAD-4.0.0 | 3.18735E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86141E-06 | 1.43583E-05 | 0 |
| M/V | rs756902355  |
-1.349 | None | N | 0.091 | 0.208 | 0.180583059064 | gnomAD-2.1.1 | 7.2E-06 | None | None | None | None | I | None | 8.3E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| M/V | rs756902355 |
-1.349 | None | N | 0.091 | 0.208 | 0.180583059064 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| M/V | rs756902355 |
-1.349 | None | N | 0.091 | 0.208 | 0.180583059064 | gnomAD-4.0.0 | 2.5655E-06 | None | None | None | None | I | None | 3.38249E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.5709 | likely_pathogenic | 0.5729 | pathogenic | -1.485 | Destabilizing | 0.002 | N | 0.295 | neutral | None | None | None | None | I |
| M/C | 0.8518 | likely_pathogenic | 0.8451 | pathogenic | -1.439 | Destabilizing | 0.497 | N | 0.523 | neutral | None | None | None | None | I |
| M/D | 0.9662 | likely_pathogenic | 0.9667 | pathogenic | -0.71 | Destabilizing | 0.22 | N | 0.595 | neutral | None | None | None | None | I |
| M/E | 0.8344 | likely_pathogenic | 0.8318 | pathogenic | -0.67 | Destabilizing | 0.085 | N | 0.449 | neutral | None | None | None | None | I |
| M/F | 0.2907 | likely_benign | 0.356 | ambiguous | -0.682 | Destabilizing | 0.009 | N | 0.359 | neutral | None | None | None | None | I |
| M/G | 0.8379 | likely_pathogenic | 0.8412 | pathogenic | -1.803 | Destabilizing | 0.037 | N | 0.49 | neutral | None | None | None | None | I |
| M/H | 0.7955 | likely_pathogenic | 0.8064 | pathogenic | -1.124 | Destabilizing | 0.497 | N | 0.533 | neutral | None | None | None | None | I |
| M/I | 0.2508 | likely_benign | 0.2434 | benign | -0.667 | Destabilizing | None | N | 0.095 | neutral | N | 0.454134614 | None | None | I |
| M/K | 0.54 | ambiguous | 0.5175 | ambiguous | -0.37 | Destabilizing | 0.028 | N | 0.421 | neutral | N | 0.484110804 | None | None | I |
| M/L | 0.1047 | likely_benign | 0.0986 | benign | -0.667 | Destabilizing | None | N | 0.073 | neutral | N | 0.353738333 | None | None | I |
| M/N | 0.8198 | likely_pathogenic | 0.8222 | pathogenic | -0.284 | Destabilizing | 0.22 | N | 0.546 | neutral | None | None | None | None | I |
| M/P | 0.7634 | likely_pathogenic | 0.7898 | pathogenic | -0.913 | Destabilizing | 0.22 | N | 0.548 | neutral | None | None | None | None | I |
| M/Q | 0.5512 | ambiguous | 0.5622 | ambiguous | -0.361 | Destabilizing | 0.22 | N | 0.489 | neutral | None | None | None | None | I |
| M/R | 0.5528 | ambiguous | 0.5319 | ambiguous | -0.099 | Destabilizing | 0.065 | N | 0.492 | neutral | N | 0.484804237 | None | None | I |
| M/S | 0.7226 | likely_pathogenic | 0.7325 | pathogenic | -0.867 | Destabilizing | 0.037 | N | 0.424 | neutral | None | None | None | None | I |
| M/T | 0.4544 | ambiguous | 0.4507 | ambiguous | -0.713 | Destabilizing | 0.014 | N | 0.387 | neutral | N | 0.46587176 | None | None | I |
| M/V | 0.0799 | likely_benign | 0.0743 | benign | -0.913 | Destabilizing | None | N | 0.091 | neutral | N | 0.44336026 | None | None | I |
| M/W | 0.7141 | likely_pathogenic | 0.7672 | pathogenic | -0.689 | Destabilizing | 0.788 | D | 0.505 | neutral | None | None | None | None | I |
| M/Y | 0.6739 | likely_pathogenic | 0.7219 | pathogenic | -0.6 | Destabilizing | 0.085 | N | 0.492 | 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.