Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23542 | 70849;70850;70851 | chr2:178575508;178575507;178575506 | chr2:179440235;179440234;179440233 |
| N2AB | 21901 | 65926;65927;65928 | chr2:178575508;178575507;178575506 | chr2:179440235;179440234;179440233 |
| N2A | 20974 | 63145;63146;63147 | chr2:178575508;178575507;178575506 | chr2:179440235;179440234;179440233 |
| N2B | 14477 | 43654;43655;43656 | chr2:178575508;178575507;178575506 | chr2:179440235;179440234;179440233 |
| Novex-1 | 14602 | 44029;44030;44031 | chr2:178575508;178575507;178575506 | chr2:179440235;179440234;179440233 |
| Novex-2 | 14669 | 44230;44231;44232 | chr2:178575508;178575507;178575506 | chr2:179440235;179440234;179440233 |
| 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 | 0.132 | N | 0.313 | 0.19 | 0.483521307902 | gnomAD-4.0.0 | 6.84243E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15947E-05 | 0 |
| M/R | rs727503570  |
None | 0.398 | N | 0.381 | 0.197 | 0.520056377819 | gnomAD-4.0.0 | 6.84243E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99531E-07 | 0 | 0 |
| M/T | rs727503570 |
None | None | N | 0.126 | 0.212 | 0.577929125939 | gnomAD-4.0.0 | 1.36849E-06 | None | None | None | None | N | None | 2.98811E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99531E-07 | 0 | 0 |
| M/V | rs878918075 |
None | None | N | 0.072 | 0.247 | None | gnomAD-4.0.0 | 1.59144E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85891E-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 | 0.3123 | likely_benign | 0.3193 | benign | -0.357 | Destabilizing | 0.089 | N | 0.201 | neutral | None | None | None | None | N |
| M/C | 0.7211 | likely_pathogenic | 0.7428 | pathogenic | -0.337 | Destabilizing | 0.959 | D | 0.321 | neutral | None | None | None | None | N |
| M/D | 0.8177 | likely_pathogenic | 0.817 | pathogenic | 0.438 | Stabilizing | 0.398 | N | 0.377 | neutral | None | None | None | None | N |
| M/E | 0.4878 | ambiguous | 0.4818 | ambiguous | 0.379 | Stabilizing | 0.211 | N | 0.323 | neutral | None | None | None | None | N |
| M/F | 0.522 | ambiguous | 0.5154 | ambiguous | -0.099 | Destabilizing | 0.048 | N | 0.299 | neutral | None | None | None | None | N |
| M/G | 0.5635 | ambiguous | 0.5688 | pathogenic | -0.517 | Destabilizing | 0.688 | D | 0.368 | neutral | None | None | None | None | N |
| M/H | 0.5682 | likely_pathogenic | 0.5682 | pathogenic | 0.262 | Stabilizing | 0.907 | D | 0.297 | neutral | None | None | None | None | N |
| M/I | 0.3664 | ambiguous | 0.3481 | ambiguous | -0.036 | Destabilizing | 0.03 | N | 0.235 | neutral | N | 0.415141003 | None | None | N |
| M/K | 0.1825 | likely_benign | 0.1847 | benign | 0.522 | Stabilizing | 0.132 | N | 0.313 | neutral | N | 0.438151149 | None | None | N |
| M/L | 0.1301 | likely_benign | 0.1268 | benign | -0.036 | Destabilizing | 0.006 | N | 0.169 | neutral | N | 0.388378476 | None | None | N |
| M/N | 0.5293 | ambiguous | 0.5284 | ambiguous | 0.656 | Stabilizing | 0.398 | N | 0.363 | neutral | None | None | None | None | N |
| M/P | 0.8715 | likely_pathogenic | 0.8804 | pathogenic | -0.114 | Destabilizing | 0.669 | D | 0.403 | neutral | None | None | None | None | N |
| M/Q | 0.2503 | likely_benign | 0.2525 | benign | 0.489 | Stabilizing | 0.736 | D | 0.293 | neutral | None | None | None | None | N |
| M/R | 0.2058 | likely_benign | 0.2062 | benign | 0.993 | Stabilizing | 0.398 | N | 0.381 | neutral | N | 0.456622266 | None | None | N |
| M/S | 0.3502 | ambiguous | 0.3613 | ambiguous | 0.198 | Stabilizing | 0.183 | N | 0.345 | neutral | None | None | None | None | N |
| M/T | 0.1114 | likely_benign | 0.1135 | benign | 0.241 | Stabilizing | None | N | 0.126 | neutral | N | 0.342219325 | None | None | N |
| M/V | 0.0903 | likely_benign | 0.0914 | benign | -0.114 | Destabilizing | None | N | 0.072 | neutral | N | 0.375275893 | None | None | N |
| M/W | 0.7487 | likely_pathogenic | 0.7369 | pathogenic | -0.088 | Destabilizing | 0.992 | D | 0.303 | neutral | None | None | None | None | N |
| M/Y | 0.7429 | likely_pathogenic | 0.7374 | pathogenic | 0.088 | Stabilizing | 0.811 | D | 0.397 | 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.