Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31351 | 94276;94277;94278 | chr2:178547575;178547574;178547573 | chr2:179412302;179412301;179412300 |
| N2AB | 29710 | 89353;89354;89355 | chr2:178547575;178547574;178547573 | chr2:179412302;179412301;179412300 |
| N2A | 28783 | 86572;86573;86574 | chr2:178547575;178547574;178547573 | chr2:179412302;179412301;179412300 |
| N2B | 22286 | 67081;67082;67083 | chr2:178547575;178547574;178547573 | chr2:179412302;179412301;179412300 |
| Novex-1 | 22411 | 67456;67457;67458 | chr2:178547575;178547574;178547573 | chr2:179412302;179412301;179412300 |
| Novex-2 | 22478 | 67657;67658;67659 | chr2:178547575;178547574;178547573 | chr2:179412302;179412301;179412300 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/L | rs794729536  |
-0.077 | 1.0 | N | 0.665 | 0.411 | 0.529813890454 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| S/L | rs794729536 |
-0.077 | 1.0 | N | 0.665 | 0.411 | 0.529813890454 | gnomAD-4.0.0 | 1.36839E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.70894E-05 | 1.15934E-05 | 0 |
| S/T | None | None | 0.999 | N | 0.566 | 0.325 | 0.277730125212 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.083 | likely_benign | 0.0996 | benign | -0.423 | Destabilizing | 0.997 | D | 0.535 | neutral | N | 0.476074819 | None | None | N |
| S/C | 0.1678 | likely_benign | 0.1961 | benign | -0.285 | Destabilizing | 1.0 | D | 0.65 | neutral | None | None | None | None | N |
| S/D | 0.6772 | likely_pathogenic | 0.7326 | pathogenic | 0.018 | Stabilizing | 0.999 | D | 0.641 | neutral | None | None | None | None | N |
| S/E | 0.7499 | likely_pathogenic | 0.7846 | pathogenic | -0.065 | Destabilizing | 0.999 | D | 0.635 | neutral | None | None | None | None | N |
| S/F | 0.3721 | ambiguous | 0.4655 | ambiguous | -0.893 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | N |
| S/G | 0.1286 | likely_benign | 0.1373 | benign | -0.566 | Destabilizing | 0.999 | D | 0.557 | neutral | None | None | None | None | N |
| S/H | 0.5852 | likely_pathogenic | 0.6248 | pathogenic | -1.063 | Destabilizing | 1.0 | D | 0.666 | neutral | None | None | None | None | N |
| S/I | 0.2408 | likely_benign | 0.3121 | benign | -0.172 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | N |
| S/K | 0.8291 | likely_pathogenic | 0.8542 | pathogenic | -0.599 | Destabilizing | 0.999 | D | 0.638 | neutral | None | None | None | None | N |
| S/L | 0.1377 | likely_benign | 0.1784 | benign | -0.172 | Destabilizing | 1.0 | D | 0.665 | neutral | N | 0.481269995 | None | None | N |
| S/M | 0.247 | likely_benign | 0.2896 | benign | 0.104 | Stabilizing | 1.0 | D | 0.665 | neutral | None | None | None | None | N |
| S/N | 0.2221 | likely_benign | 0.2728 | benign | -0.284 | Destabilizing | 0.999 | D | 0.635 | neutral | None | None | None | None | N |
| S/P | 0.5074 | ambiguous | 0.5534 | ambiguous | -0.226 | Destabilizing | 1.0 | D | 0.659 | neutral | N | 0.487793322 | None | None | N |
| S/Q | 0.6916 | likely_pathogenic | 0.7166 | pathogenic | -0.549 | Destabilizing | 1.0 | D | 0.679 | prob.neutral | None | None | None | None | N |
| S/R | 0.7955 | likely_pathogenic | 0.8249 | pathogenic | -0.367 | Destabilizing | 1.0 | D | 0.652 | neutral | None | None | None | None | N |
| S/T | 0.0913 | likely_benign | 0.1082 | benign | -0.39 | Destabilizing | 0.999 | D | 0.566 | neutral | N | 0.427686226 | None | None | N |
| S/V | 0.2367 | likely_benign | 0.2993 | benign | -0.226 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | N |
| S/W | 0.5561 | ambiguous | 0.6088 | pathogenic | -0.878 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | N | 0.500628762 | None | None | N |
| S/Y | 0.321 | likely_benign | 0.3942 | ambiguous | -0.619 | Destabilizing | 1.0 | D | 0.728 | prob.delet. | 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.