Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17972 | 54139;54140;54141 | chr2:178605263;178605262;178605261 | chr2:179469990;179469989;179469988 |
| N2AB | 16331 | 49216;49217;49218 | chr2:178605263;178605262;178605261 | chr2:179469990;179469989;179469988 |
| N2A | 15404 | 46435;46436;46437 | chr2:178605263;178605262;178605261 | chr2:179469990;179469989;179469988 |
| N2B | 8907 | 26944;26945;26946 | chr2:178605263;178605262;178605261 | chr2:179469990;179469989;179469988 |
| Novex-1 | 9032 | 27319;27320;27321 | chr2:178605263;178605262;178605261 | chr2:179469990;179469989;179469988 |
| Novex-2 | 9099 | 27520;27521;27522 | chr2:178605263;178605262;178605261 | chr2:179469990;179469989;179469988 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/Q | rs377169251  |
-0.124 | 0.985 | N | 0.586 | 0.265 | None | gnomAD-2.1.1 | 1.27E-05 | None | None | None | None | N | None | 6.69E-05 | 0 | None | 0 | 1.16198E-04 | None | 0 | None | 0 | 0 | 0 |
| R/Q | rs377169251 |
-0.124 | 0.985 | N | 0.586 | 0.265 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 4.84E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/Q | rs377169251 |
-0.124 | 0.985 | N | 0.586 | 0.265 | None | gnomAD-4.0.0 | 1.06232E-05 | None | None | None | None | N | None | 2.69121E-05 | 0 | None | 0 | 4.50897E-05 | None | 0 | 0 | 7.66943E-06 | 3.36768E-05 | 1.61723E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.5544 | ambiguous | 0.5818 | pathogenic | -0.138 | Destabilizing | 0.863 | D | 0.575 | neutral | None | None | None | None | N |
| R/C | 0.458 | ambiguous | 0.4539 | ambiguous | -0.498 | Destabilizing | 0.999 | D | 0.615 | neutral | None | None | None | None | N |
| R/D | 0.7841 | likely_pathogenic | 0.8006 | pathogenic | -0.48 | Destabilizing | 0.969 | D | 0.609 | neutral | None | None | None | None | N |
| R/E | 0.5323 | ambiguous | 0.5431 | ambiguous | -0.464 | Destabilizing | 0.863 | D | 0.612 | neutral | None | None | None | None | N |
| R/F | 0.6877 | likely_pathogenic | 0.7286 | pathogenic | -0.523 | Destabilizing | 0.997 | D | 0.619 | neutral | None | None | None | None | N |
| R/G | 0.4343 | ambiguous | 0.4467 | ambiguous | -0.215 | Destabilizing | 0.983 | D | 0.558 | neutral | N | 0.470216 | None | None | N |
| R/H | 0.2249 | likely_benign | 0.2076 | benign | -0.679 | Destabilizing | 0.997 | D | 0.607 | neutral | None | None | None | None | N |
| R/I | 0.4586 | ambiguous | 0.5026 | ambiguous | 0.019 | Stabilizing | 0.997 | D | 0.625 | neutral | None | None | None | None | N |
| R/K | 0.1409 | likely_benign | 0.1563 | benign | -0.475 | Destabilizing | 0.028 | N | 0.233 | neutral | None | None | None | None | N |
| R/L | 0.4272 | ambiguous | 0.4454 | ambiguous | 0.019 | Stabilizing | 0.983 | D | 0.558 | neutral | N | 0.451110164 | None | None | N |
| R/M | 0.4704 | ambiguous | 0.5074 | ambiguous | -0.33 | Destabilizing | 0.997 | D | 0.622 | neutral | None | None | None | None | N |
| R/N | 0.7211 | likely_pathogenic | 0.7593 | pathogenic | -0.437 | Destabilizing | 0.969 | D | 0.569 | neutral | None | None | None | None | N |
| R/P | 0.5312 | ambiguous | 0.5421 | ambiguous | -0.02 | Destabilizing | 0.998 | D | 0.624 | neutral | N | 0.418805745 | None | None | N |
| R/Q | 0.1892 | likely_benign | 0.1792 | benign | -0.425 | Destabilizing | 0.985 | D | 0.586 | neutral | N | 0.46917585 | None | None | N |
| R/S | 0.6751 | likely_pathogenic | 0.7028 | pathogenic | -0.524 | Destabilizing | 0.939 | D | 0.57 | neutral | None | None | None | None | N |
| R/T | 0.4239 | ambiguous | 0.4505 | ambiguous | -0.437 | Destabilizing | 0.969 | D | 0.556 | neutral | None | None | None | None | N |
| R/V | 0.5202 | ambiguous | 0.5632 | ambiguous | -0.02 | Destabilizing | 0.991 | D | 0.602 | neutral | None | None | None | None | N |
| R/W | 0.3392 | likely_benign | 0.3266 | benign | -0.771 | Destabilizing | 0.999 | D | 0.645 | neutral | None | None | None | None | N |
| R/Y | 0.5583 | ambiguous | 0.5828 | pathogenic | -0.414 | Destabilizing | 0.997 | D | 0.63 | 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.