Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25519 | 76780;76781;76782 | chr2:178569577;178569576;178569575 | chr2:179434304;179434303;179434302 |
| N2AB | 23878 | 71857;71858;71859 | chr2:178569577;178569576;178569575 | chr2:179434304;179434303;179434302 |
| N2A | 22951 | 69076;69077;69078 | chr2:178569577;178569576;178569575 | chr2:179434304;179434303;179434302 |
| N2B | 16454 | 49585;49586;49587 | chr2:178569577;178569576;178569575 | chr2:179434304;179434303;179434302 |
| Novex-1 | 16579 | 49960;49961;49962 | chr2:178569577;178569576;178569575 | chr2:179434304;179434303;179434302 |
| Novex-2 | 16646 | 50161;50162;50163 | chr2:178569577;178569576;178569575 | chr2:179434304;179434303;179434302 |
| 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/N | rs376185524  |
None | 0.055 | N | 0.459 | 0.217 | 0.627368885312 | gnomAD-4.0.0 | 2.05366E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69906E-06 | 0 | 0 |
| I/T | rs376185524 |
-0.866 | 0.012 | N | 0.443 | 0.153 | None | gnomAD-2.1.1 | 4.86E-05 | None | None | None | None | I | None | 0 | 1.16496E-04 | None | 0 | 0 | None | 3.28E-05 | None | 0 | 5.37E-05 | 1.6728E-04 |
| I/T | rs376185524 |
-0.866 | 0.012 | N | 0.443 | 0.153 | None | 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 | rs376185524 |
-0.866 | 0.012 | N | 0.443 | 0.153 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| I/T | rs376185524 |
-0.866 | 0.012 | N | 0.443 | 0.153 | None | gnomAD-4.0.0 | 2.41808E-05 | None | None | None | None | I | None | 0 | 6.67802E-05 | None | 0 | 0 | None | 0 | 1.65289E-04 | 2.62835E-05 | 1.09888E-05 | 3.2039E-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 | 0.2368 | likely_benign | 0.2438 | benign | -0.835 | Destabilizing | 0.007 | N | 0.314 | neutral | None | None | None | None | I |
| I/C | 0.4676 | ambiguous | 0.4994 | ambiguous | -0.647 | Destabilizing | 0.356 | N | 0.397 | neutral | None | None | None | None | I |
| I/D | 0.6226 | likely_pathogenic | 0.6531 | pathogenic | -0.064 | Destabilizing | 0.072 | N | 0.469 | neutral | None | None | None | None | I |
| I/E | 0.5646 | likely_pathogenic | 0.6015 | pathogenic | -0.132 | Destabilizing | 0.072 | N | 0.444 | neutral | None | None | None | None | I |
| I/F | 0.1466 | likely_benign | 0.1534 | benign | -0.663 | Destabilizing | 0.055 | N | 0.323 | neutral | N | 0.476429896 | None | None | I |
| I/G | 0.3985 | ambiguous | 0.4278 | ambiguous | -1.045 | Destabilizing | 0.038 | N | 0.476 | neutral | None | None | None | None | I |
| I/H | 0.4526 | ambiguous | 0.473 | ambiguous | -0.277 | Destabilizing | 0.628 | D | 0.399 | neutral | None | None | None | None | I |
| I/K | 0.4339 | ambiguous | 0.4754 | ambiguous | -0.451 | Destabilizing | 0.072 | N | 0.462 | neutral | None | None | None | None | I |
| I/L | 0.1061 | likely_benign | 0.1104 | benign | -0.388 | Destabilizing | 0.002 | N | 0.249 | neutral | N | 0.427577157 | None | None | I |
| I/M | 0.077 | likely_benign | 0.0779 | benign | -0.395 | Destabilizing | 0.001 | N | 0.201 | neutral | N | 0.44125853 | None | None | I |
| I/N | 0.1519 | likely_benign | 0.1563 | benign | -0.227 | Destabilizing | 0.055 | N | 0.459 | neutral | N | 0.439911736 | None | None | I |
| I/P | 0.6148 | likely_pathogenic | 0.6234 | pathogenic | -0.503 | Destabilizing | 0.356 | N | 0.47 | neutral | None | None | None | None | I |
| I/Q | 0.3866 | ambiguous | 0.4031 | ambiguous | -0.429 | Destabilizing | 0.214 | N | 0.466 | neutral | None | None | None | None | I |
| I/R | 0.3768 | ambiguous | 0.4148 | ambiguous | 0.088 | Stabilizing | 0.214 | N | 0.468 | neutral | None | None | None | None | I |
| I/S | 0.1949 | likely_benign | 0.1999 | benign | -0.769 | Destabilizing | 0.001 | N | 0.283 | neutral | N | 0.427521229 | None | None | I |
| I/T | 0.1427 | likely_benign | 0.1305 | benign | -0.723 | Destabilizing | 0.012 | N | 0.443 | neutral | N | 0.403124216 | None | None | I |
| I/V | 0.0598 | likely_benign | 0.0638 | benign | -0.503 | Destabilizing | None | N | 0.196 | neutral | N | 0.397737039 | None | None | I |
| I/W | 0.7187 | likely_pathogenic | 0.7489 | pathogenic | -0.672 | Destabilizing | 0.864 | D | 0.397 | neutral | None | None | None | None | I |
| I/Y | 0.402 | ambiguous | 0.4369 | ambiguous | -0.434 | Destabilizing | 0.356 | N | 0.451 | 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.