Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15192 | 45799;45800;45801 | chr2:178621144;178621143;178621142 | chr2:179485871;179485870;179485869 |
| N2AB | 13551 | 40876;40877;40878 | chr2:178621144;178621143;178621142 | chr2:179485871;179485870;179485869 |
| N2A | 12624 | 38095;38096;38097 | chr2:178621144;178621143;178621142 | chr2:179485871;179485870;179485869 |
| N2B | 6127 | 18604;18605;18606 | chr2:178621144;178621143;178621142 | chr2:179485871;179485870;179485869 |
| Novex-1 | 6252 | 18979;18980;18981 | chr2:178621144;178621143;178621142 | chr2:179485871;179485870;179485869 |
| Novex-2 | 6319 | 19180;19181;19182 | chr2:178621144;178621143;178621142 | chr2:179485871;179485870;179485869 |
| 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 | rs1559876731  |
None | 0.028 | N | 0.249 | 0.177 | 0.694280915357 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.93E-06 | 0 |
| M/I | rs1559876731 |
None | 0.028 | N | 0.249 | 0.177 | 0.694280915357 | gnomAD-4.0.0 | 1.59375E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86161E-06 | 0 | 0 |
| M/T | None | None | 0.028 | N | 0.252 | 0.168 | 0.752934275728 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 | 0.4492 | ambiguous | 0.4753 | ambiguous | -2.078 | Highly Destabilizing | 0.55 | D | 0.294 | neutral | None | None | None | None | N |
| M/C | 0.8194 | likely_pathogenic | 0.7846 | pathogenic | -1.827 | Destabilizing | 0.993 | D | 0.477 | neutral | None | None | None | None | N |
| M/D | 0.8365 | likely_pathogenic | 0.8497 | pathogenic | -1.414 | Destabilizing | 0.932 | D | 0.554 | neutral | None | None | None | None | N |
| M/E | 0.4938 | ambiguous | 0.502 | ambiguous | -1.257 | Destabilizing | 0.737 | D | 0.485 | neutral | None | None | None | None | N |
| M/F | 0.4513 | ambiguous | 0.4742 | ambiguous | -0.655 | Destabilizing | 0.872 | D | 0.492 | neutral | None | None | None | None | N |
| M/G | 0.7599 | likely_pathogenic | 0.7746 | pathogenic | -2.511 | Highly Destabilizing | 0.85 | D | 0.496 | neutral | None | None | None | None | N |
| M/H | 0.5974 | likely_pathogenic | 0.6293 | pathogenic | -1.915 | Destabilizing | 0.993 | D | 0.529 | neutral | None | None | None | None | N |
| M/I | 0.4117 | ambiguous | 0.4328 | ambiguous | -0.876 | Destabilizing | 0.028 | N | 0.249 | neutral | N | 0.447879999 | None | None | N |
| M/K | 0.3633 | ambiguous | 0.3906 | ambiguous | -1.164 | Destabilizing | 0.028 | N | 0.251 | neutral | N | 0.476576009 | None | None | N |
| M/L | 0.1813 | likely_benign | 0.1871 | benign | -0.876 | Destabilizing | 0.002 | N | 0.171 | neutral | N | 0.492697053 | None | None | N |
| M/N | 0.5353 | ambiguous | 0.5772 | pathogenic | -1.293 | Destabilizing | 0.932 | D | 0.551 | neutral | None | None | None | None | N |
| M/P | 0.9798 | likely_pathogenic | 0.9843 | pathogenic | -1.254 | Destabilizing | 0.977 | D | 0.57 | neutral | None | None | None | None | N |
| M/Q | 0.3286 | likely_benign | 0.355 | ambiguous | -1.135 | Destabilizing | 0.872 | D | 0.508 | neutral | None | None | None | None | N |
| M/R | 0.3922 | ambiguous | 0.4143 | ambiguous | -1.017 | Destabilizing | 0.719 | D | 0.52 | neutral | N | 0.489730102 | None | None | N |
| M/S | 0.4016 | ambiguous | 0.432 | ambiguous | -1.925 | Destabilizing | 0.584 | D | 0.405 | neutral | None | None | None | None | N |
| M/T | 0.1784 | likely_benign | 0.1935 | benign | -1.648 | Destabilizing | 0.028 | N | 0.252 | neutral | N | 0.481333785 | None | None | N |
| M/V | 0.1214 | likely_benign | 0.1296 | benign | -1.254 | Destabilizing | 0.028 | N | 0.197 | neutral | N | 0.441381949 | None | None | N |
| M/W | 0.7464 | likely_pathogenic | 0.7472 | pathogenic | -0.85 | Destabilizing | 0.998 | D | 0.467 | neutral | None | None | None | None | N |
| M/Y | 0.729 | likely_pathogenic | 0.7421 | pathogenic | -0.846 | Destabilizing | 0.977 | D | 0.534 | neutral | None | None | None | None | N |
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.