Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26752 | 80479;80480;80481 | chr2:178565878;178565877;178565876 | chr2:179430605;179430604;179430603 |
| N2AB | 25111 | 75556;75557;75558 | chr2:178565878;178565877;178565876 | chr2:179430605;179430604;179430603 |
| N2A | 24184 | 72775;72776;72777 | chr2:178565878;178565877;178565876 | chr2:179430605;179430604;179430603 |
| N2B | 17687 | 53284;53285;53286 | chr2:178565878;178565877;178565876 | chr2:179430605;179430604;179430603 |
| Novex-1 | 17812 | 53659;53660;53661 | chr2:178565878;178565877;178565876 | chr2:179430605;179430604;179430603 |
| Novex-2 | 17879 | 53860;53861;53862 | chr2:178565878;178565877;178565876 | chr2:179430605;179430604;179430603 |
| 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/V | rs376046847  |
None | 0.099 | N | 0.261 | 0.073 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs376046847 |
None | 0.099 | N | 0.261 | 0.073 | None | gnomAD-4.0.0 | 3.04501E-06 | None | None | None | None | N | None | 3.49443E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.20496E-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 | 0.2038 | likely_benign | 0.2028 | benign | -1.763 | Destabilizing | 0.25 | N | 0.412 | neutral | None | None | None | None | N |
| I/C | 0.5099 | ambiguous | 0.5284 | ambiguous | -0.882 | Destabilizing | 0.992 | D | 0.498 | neutral | None | None | None | None | N |
| I/D | 0.6594 | likely_pathogenic | 0.6341 | pathogenic | -0.894 | Destabilizing | 0.85 | D | 0.559 | neutral | None | None | None | None | N |
| I/E | 0.5961 | likely_pathogenic | 0.5744 | pathogenic | -0.845 | Destabilizing | 0.447 | N | 0.536 | neutral | None | None | None | None | N |
| I/F | 0.1634 | likely_benign | 0.1486 | benign | -1.127 | Destabilizing | 0.81 | D | 0.531 | neutral | N | 0.447157421 | None | None | N |
| I/G | 0.4581 | ambiguous | 0.4549 | ambiguous | -2.136 | Highly Destabilizing | 0.617 | D | 0.555 | neutral | None | None | None | None | N |
| I/H | 0.4918 | ambiguous | 0.474 | ambiguous | -1.308 | Destabilizing | 0.977 | D | 0.581 | neutral | None | None | None | None | N |
| I/K | 0.5174 | ambiguous | 0.4534 | ambiguous | -1.0 | Destabilizing | 0.447 | N | 0.532 | neutral | None | None | None | None | N |
| I/L | 0.1021 | likely_benign | 0.0969 | benign | -0.784 | Destabilizing | 0.002 | N | 0.12 | neutral | N | 0.426262074 | None | None | N |
| I/M | 0.0935 | likely_benign | 0.0863 | benign | -0.545 | Destabilizing | 0.036 | N | 0.239 | neutral | N | 0.460894723 | None | None | N |
| I/N | 0.1927 | likely_benign | 0.203 | benign | -0.833 | Destabilizing | 0.81 | D | 0.564 | neutral | N | 0.437977791 | None | None | N |
| I/P | 0.6302 | likely_pathogenic | 0.6407 | pathogenic | -1.08 | Destabilizing | 0.92 | D | 0.575 | neutral | None | None | None | None | N |
| I/Q | 0.4462 | ambiguous | 0.4284 | ambiguous | -0.949 | Destabilizing | 0.048 | N | 0.4 | neutral | None | None | None | None | N |
| I/R | 0.4335 | ambiguous | 0.3685 | ambiguous | -0.498 | Destabilizing | 0.739 | D | 0.559 | neutral | None | None | None | None | N |
| I/S | 0.1677 | likely_benign | 0.1756 | benign | -1.563 | Destabilizing | 0.379 | N | 0.466 | neutral | N | 0.3831833 | None | None | N |
| I/T | 0.1379 | likely_benign | 0.1488 | benign | -1.393 | Destabilizing | 0.004 | N | 0.285 | neutral | N | 0.396573885 | None | None | N |
| I/V | 0.0628 | likely_benign | 0.0624 | benign | -1.08 | Destabilizing | 0.099 | N | 0.261 | neutral | N | 0.467185977 | None | None | N |
| I/W | 0.7614 | likely_pathogenic | 0.7306 | pathogenic | -1.235 | Destabilizing | 0.992 | D | 0.608 | neutral | None | None | None | None | N |
| I/Y | 0.4597 | ambiguous | 0.4467 | ambiguous | -0.996 | Destabilizing | 0.92 | D | 0.523 | 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.