Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31517 | 94774;94775;94776 | chr2:178546879;178546878;178546877 | chr2:179411606;179411605;179411604 |
| N2AB | 29876 | 89851;89852;89853 | chr2:178546879;178546878;178546877 | chr2:179411606;179411605;179411604 |
| N2A | 28949 | 87070;87071;87072 | chr2:178546879;178546878;178546877 | chr2:179411606;179411605;179411604 |
| N2B | 22452 | 67579;67580;67581 | chr2:178546879;178546878;178546877 | chr2:179411606;179411605;179411604 |
| Novex-1 | 22577 | 67954;67955;67956 | chr2:178546879;178546878;178546877 | chr2:179411606;179411605;179411604 |
| Novex-2 | 22644 | 68155;68156;68157 | chr2:178546879;178546878;178546877 | chr2:179411606;179411605;179411604 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/N | rs754507654  |
0.334 | 0.884 | N | 0.27 | 0.232 | 0.219573609325 | gnomAD-2.1.1 | 4.26E-06 | None | None | None | None | N | None | 6.5E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/N | rs754507654 |
0.334 | 0.884 | N | 0.27 | 0.232 | 0.219573609325 | gnomAD-4.0.0 | 1.64601E-06 | None | None | None | None | N | None | 5.76768E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.3261 | likely_benign | 0.321 | benign | -0.273 | Destabilizing | 0.999 | D | 0.63 | neutral | N | 0.490332195 | None | None | N |
| D/C | 0.8433 | likely_pathogenic | 0.8455 | pathogenic | 0.189 | Stabilizing | 1.0 | D | 0.66 | neutral | None | None | None | None | N |
| D/E | 0.3359 | likely_benign | 0.3149 | benign | -0.283 | Destabilizing | 0.996 | D | 0.437 | neutral | N | 0.463702954 | None | None | N |
| D/F | 0.8693 | likely_pathogenic | 0.8594 | pathogenic | -0.306 | Destabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | N |
| D/G | 0.3663 | ambiguous | 0.3701 | ambiguous | -0.463 | Destabilizing | 0.996 | D | 0.625 | neutral | N | 0.496951523 | None | None | N |
| D/H | 0.5718 | likely_pathogenic | 0.5509 | ambiguous | -0.261 | Destabilizing | 1.0 | D | 0.669 | neutral | N | 0.483778728 | None | None | N |
| D/I | 0.7905 | likely_pathogenic | 0.751 | pathogenic | 0.177 | Stabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | N |
| D/K | 0.8038 | likely_pathogenic | 0.7766 | pathogenic | 0.474 | Stabilizing | 0.999 | D | 0.663 | neutral | None | None | None | None | N |
| D/L | 0.7498 | likely_pathogenic | 0.7221 | pathogenic | 0.177 | Stabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | N |
| D/M | 0.8525 | likely_pathogenic | 0.8296 | pathogenic | 0.398 | Stabilizing | 1.0 | D | 0.648 | neutral | None | None | None | None | N |
| D/N | 0.1528 | likely_benign | 0.1504 | benign | 0.168 | Stabilizing | 0.884 | D | 0.27 | neutral | N | 0.449312292 | None | None | N |
| D/P | 0.9926 | likely_pathogenic | 0.992 | pathogenic | 0.049 | Stabilizing | 1.0 | D | 0.728 | prob.delet. | None | None | None | None | N |
| D/Q | 0.6731 | likely_pathogenic | 0.6579 | pathogenic | 0.189 | Stabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | N |
| D/R | 0.7757 | likely_pathogenic | 0.7551 | pathogenic | 0.515 | Stabilizing | 1.0 | D | 0.677 | prob.neutral | None | None | None | None | N |
| D/S | 0.2137 | likely_benign | 0.2018 | benign | 0.077 | Stabilizing | 0.997 | D | 0.597 | neutral | None | None | None | None | N |
| D/T | 0.5286 | ambiguous | 0.4948 | ambiguous | 0.228 | Stabilizing | 0.999 | D | 0.667 | neutral | None | None | None | None | N |
| D/V | 0.56 | ambiguous | 0.5154 | ambiguous | 0.049 | Stabilizing | 1.0 | D | 0.7 | prob.neutral | N | 0.508515311 | None | None | N |
| D/W | 0.9746 | likely_pathogenic | 0.9723 | pathogenic | -0.193 | Destabilizing | 1.0 | D | 0.672 | neutral | None | None | None | None | N |
| D/Y | 0.5578 | ambiguous | 0.5363 | ambiguous | -0.066 | Destabilizing | 1.0 | D | 0.663 | neutral | N | 0.508466348 | 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.