Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28358 | 85297;85298;85299 | chr2:178561060;178561059;178561058 | chr2:179425787;179425786;179425785 |
| N2AB | 26717 | 80374;80375;80376 | chr2:178561060;178561059;178561058 | chr2:179425787;179425786;179425785 |
| N2A | 25790 | 77593;77594;77595 | chr2:178561060;178561059;178561058 | chr2:179425787;179425786;179425785 |
| N2B | 19293 | 58102;58103;58104 | chr2:178561060;178561059;178561058 | chr2:179425787;179425786;179425785 |
| Novex-1 | 19418 | 58477;58478;58479 | chr2:178561060;178561059;178561058 | chr2:179425787;179425786;179425785 |
| Novex-2 | 19485 | 58678;58679;58680 | chr2:178561060;178561059;178561058 | chr2:179425787;179425786;179425785 |
| 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/I | rs973736756  |
None | None | N | 0.069 | 0.122 | 0.432493127443 | gnomAD-4.0.0 | 1.36835E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79889E-06 | 0 | 0 |
| M/K | None | 0.896 | None | N | 0.137 | 0.332 | 0.542675667512 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.56E-05 | None | 0 | None | 0 | 0 | 0 |
| M/L | rs368069666 |
0.425 | 0.01 | N | 0.2 | 0.137 | 0.591025817267 | gnomAD-2.1.1 | 1.79E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.91E-05 | 0 |
| M/L | rs368069666 |
0.425 | 0.01 | N | 0.2 | 0.137 | 0.591025817267 | 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 |
| M/L | rs368069666 |
0.425 | 0.01 | N | 0.2 | 0.137 | 0.591025817267 | gnomAD-4.0.0 | 2.85046E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.81413E-05 | 0 | 1.60102E-05 |
| M/R | rs766947305 |
None | 0.112 | N | 0.313 | 0.263 | 0.548571244948 | gnomAD-4.0.0 | 1.36836E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.31868E-05 | 0 |
| M/T | rs766947305 |
0.655 | 0.001 | N | 0.134 | 0.261 | 0.67367363106 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| M/T | rs766947305 |
0.655 | 0.001 | N | 0.134 | 0.261 | 0.67367363106 | gnomAD-4.0.0 | 2.05254E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69835E-06 | 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 | 0.5178 | ambiguous | 0.5494 | ambiguous | -0.102 | Destabilizing | 0.029 | N | 0.315 | neutral | None | None | None | None | I |
| M/C | 0.7202 | likely_pathogenic | 0.7773 | pathogenic | -0.218 | Destabilizing | 0.878 | D | 0.32 | neutral | None | None | None | None | I |
| M/D | 0.767 | likely_pathogenic | 0.7988 | pathogenic | 0.383 | Stabilizing | 0.064 | N | 0.252 | neutral | None | None | None | None | I |
| M/E | 0.535 | ambiguous | 0.5691 | pathogenic | 0.31 | Stabilizing | None | N | 0.137 | neutral | None | None | None | None | I |
| M/F | 0.3746 | ambiguous | 0.4078 | ambiguous | -0.12 | Destabilizing | 0.403 | N | 0.305 | neutral | None | None | None | None | I |
| M/G | 0.7196 | likely_pathogenic | 0.7428 | pathogenic | -0.194 | Destabilizing | 0.121 | N | 0.253 | neutral | None | None | None | None | I |
| M/H | 0.5002 | ambiguous | 0.5485 | ambiguous | 0.424 | Stabilizing | 0.703 | D | 0.313 | neutral | None | None | None | None | I |
| M/I | 0.4603 | ambiguous | 0.5519 | ambiguous | 0.033 | Stabilizing | None | N | 0.069 | neutral | N | 0.454918474 | None | None | I |
| M/K | 0.2714 | likely_benign | 0.3128 | benign | 0.541 | Stabilizing | None | N | 0.137 | neutral | N | 0.473157518 | None | None | I |
| M/L | 0.1485 | likely_benign | 0.1451 | benign | 0.033 | Stabilizing | 0.01 | N | 0.2 | neutral | N | 0.473504234 | None | None | I |
| M/N | 0.498 | ambiguous | 0.5438 | ambiguous | 0.703 | Stabilizing | 0.25 | N | 0.333 | neutral | None | None | None | None | I |
| M/P | 0.9302 | likely_pathogenic | 0.9472 | pathogenic | 0.013 | Stabilizing | 0.403 | N | 0.337 | neutral | None | None | None | None | I |
| M/Q | 0.2816 | likely_benign | 0.3096 | benign | 0.526 | Stabilizing | 0.143 | N | 0.286 | neutral | None | None | None | None | I |
| M/R | 0.2864 | likely_benign | 0.3225 | benign | 0.965 | Stabilizing | 0.112 | N | 0.313 | neutral | N | 0.449339296 | None | None | I |
| M/S | 0.4385 | ambiguous | 0.4699 | ambiguous | 0.318 | Stabilizing | 0.064 | N | 0.315 | neutral | None | None | None | None | I |
| M/T | 0.2994 | likely_benign | 0.3229 | benign | 0.331 | Stabilizing | 0.001 | N | 0.134 | neutral | N | 0.433100407 | None | None | I |
| M/V | 0.143 | likely_benign | 0.1645 | benign | 0.013 | Stabilizing | 0.01 | N | 0.21 | neutral | N | 0.473504234 | None | None | I |
| M/W | 0.6823 | likely_pathogenic | 0.7087 | pathogenic | -0.145 | Destabilizing | 0.964 | D | 0.335 | neutral | None | None | None | None | I |
| M/Y | 0.5749 | likely_pathogenic | 0.6291 | pathogenic | 0.077 | Stabilizing | 0.878 | D | 0.364 | 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.