Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24933 | 75022;75023;75024 | chr2:178571335;178571334;178571333 | chr2:179436062;179436061;179436060 |
| N2AB | 23292 | 70099;70100;70101 | chr2:178571335;178571334;178571333 | chr2:179436062;179436061;179436060 |
| N2A | 22365 | 67318;67319;67320 | chr2:178571335;178571334;178571333 | chr2:179436062;179436061;179436060 |
| N2B | 15868 | 47827;47828;47829 | chr2:178571335;178571334;178571333 | chr2:179436062;179436061;179436060 |
| Novex-1 | 15993 | 48202;48203;48204 | chr2:178571335;178571334;178571333 | chr2:179436062;179436061;179436060 |
| Novex-2 | 16060 | 48403;48404;48405 | chr2:178571335;178571334;178571333 | chr2:179436062;179436061;179436060 |
| 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 | None | None | 0.001 | N | 0.337 | 0.135 | 0.602586112267 | gnomAD-4.0.0 | 1.36866E-06 | None | None | None | None | I | None | 2.99025E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99603E-07 | 0 | 0 |
| I/T | rs769422476  |
-0.333 | None | N | 0.175 | 0.114 | 0.454798141022 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 4.65E-05 | 1.78E-05 | 0 |
| I/T | rs769422476 |
-0.333 | None | N | 0.175 | 0.114 | 0.454798141022 | gnomAD-4.0.0 | 2.73732E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 1.87294E-05 | 0 | 2.69881E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.1932 | likely_benign | 0.1996 | benign | -0.419 | Destabilizing | None | N | 0.165 | neutral | None | None | None | None | I |
| I/C | 0.5733 | likely_pathogenic | 0.5978 | pathogenic | -0.807 | Destabilizing | 0.041 | N | 0.399 | neutral | None | None | None | None | I |
| I/D | 0.5409 | ambiguous | 0.5568 | ambiguous | -0.094 | Destabilizing | 0.002 | N | 0.317 | neutral | None | None | None | None | I |
| I/E | 0.4621 | ambiguous | 0.4658 | ambiguous | -0.191 | Destabilizing | 0.002 | N | 0.275 | neutral | None | None | None | None | I |
| I/F | 0.1731 | likely_benign | 0.1972 | benign | -0.6 | Destabilizing | 0.003 | N | 0.184 | neutral | N | 0.511206113 | None | None | I |
| I/G | 0.3746 | ambiguous | 0.4022 | ambiguous | -0.507 | Destabilizing | 0.001 | N | 0.207 | neutral | None | None | None | None | I |
| I/H | 0.4929 | ambiguous | 0.5074 | ambiguous | 0.071 | Stabilizing | 0.116 | N | 0.457 | neutral | None | None | None | None | I |
| I/K | 0.4079 | ambiguous | 0.4121 | ambiguous | -0.279 | Destabilizing | 0.002 | N | 0.297 | neutral | None | None | None | None | I |
| I/L | 0.0951 | likely_benign | 0.1063 | benign | -0.312 | Destabilizing | None | N | 0.089 | neutral | N | 0.428339587 | None | None | I |
| I/M | 0.1145 | likely_benign | 0.126 | benign | -0.551 | Destabilizing | 0.007 | N | 0.283 | neutral | N | 0.447696139 | None | None | I |
| I/N | 0.2298 | likely_benign | 0.2241 | benign | -0.157 | Destabilizing | 0.001 | N | 0.337 | neutral | N | 0.452216524 | None | None | I |
| I/P | 0.428 | ambiguous | 0.3944 | ambiguous | -0.32 | Destabilizing | 0.008 | N | 0.351 | neutral | None | None | None | None | I |
| I/Q | 0.3956 | ambiguous | 0.3996 | ambiguous | -0.33 | Destabilizing | 0.008 | N | 0.409 | neutral | None | None | None | None | I |
| I/R | 0.3298 | likely_benign | 0.3304 | benign | 0.155 | Stabilizing | 0.008 | N | 0.399 | neutral | None | None | None | None | I |
| I/S | 0.2024 | likely_benign | 0.2072 | benign | -0.553 | Destabilizing | None | N | 0.184 | neutral | N | 0.405289369 | None | None | I |
| I/T | 0.205 | likely_benign | 0.214 | benign | -0.55 | Destabilizing | None | N | 0.175 | neutral | N | 0.414543571 | None | None | I |
| I/V | 0.0499 | likely_benign | 0.0519 | benign | -0.32 | Destabilizing | None | N | 0.068 | neutral | N | 0.376334686 | None | None | I |
| I/W | 0.7788 | likely_pathogenic | 0.8166 | pathogenic | -0.618 | Destabilizing | 0.316 | N | 0.335 | neutral | None | None | None | None | I |
| I/Y | 0.4673 | ambiguous | 0.4838 | ambiguous | -0.381 | Destabilizing | 0.018 | N | 0.329 | 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.