Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25223 | 75892;75893;75894 | chr2:178570465;178570464;178570463 | chr2:179435192;179435191;179435190 |
| N2AB | 23582 | 70969;70970;70971 | chr2:178570465;178570464;178570463 | chr2:179435192;179435191;179435190 |
| N2A | 22655 | 68188;68189;68190 | chr2:178570465;178570464;178570463 | chr2:179435192;179435191;179435190 |
| N2B | 16158 | 48697;48698;48699 | chr2:178570465;178570464;178570463 | chr2:179435192;179435191;179435190 |
| Novex-1 | 16283 | 49072;49073;49074 | chr2:178570465;178570464;178570463 | chr2:179435192;179435191;179435190 |
| Novex-2 | 16350 | 49273;49274;49275 | chr2:178570465;178570464;178570463 | chr2:179435192;179435191;179435190 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs370070176  |
-0.029 | 0.004 | N | 0.424 | 0.094 | None | gnomAD-2.1.1 | 1.11074E-04 | None | None | None | None | N | None | 2.48221E-04 | 2.84E-05 | None | 0 | 0 | None | 7.51978E-04 | None | 0 | 0 | 1.41044E-04 |
| T/I | rs370070176 |
-0.029 | 0.004 | N | 0.424 | 0.094 | None | gnomAD-3.1.2 | 4.61E-05 | None | None | None | None | N | None | 1.2079E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 4.1425E-04 | 0 |
| T/I | rs370070176 |
-0.029 | 0.004 | N | 0.424 | 0.094 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| T/I | rs370070176 |
-0.029 | 0.004 | N | 0.424 | 0.094 | None | gnomAD-4.0.0 | 4.40112E-05 | None | None | None | None | N | None | 1.20054E-04 | 1.66817E-05 | None | 0 | 0 | None | 0 | 6.60502E-04 | 0 | 5.59972E-04 | 9.60922E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.097 | likely_benign | 0.1015 | benign | -0.888 | Destabilizing | 0.005 | N | 0.303 | neutral | N | 0.4756252 | None | None | N |
| T/C | 0.2341 | likely_benign | 0.28 | benign | -0.58 | Destabilizing | 0.001 | N | 0.38 | neutral | None | None | None | None | N |
| T/D | 0.6114 | likely_pathogenic | 0.6548 | pathogenic | -0.646 | Destabilizing | 0.072 | N | 0.509 | neutral | None | None | None | None | N |
| T/E | 0.5305 | ambiguous | 0.5656 | pathogenic | -0.636 | Destabilizing | 0.072 | N | 0.471 | neutral | None | None | None | None | N |
| T/F | 0.1301 | likely_benign | 0.15 | benign | -0.999 | Destabilizing | 0.12 | N | 0.583 | neutral | None | None | None | None | N |
| T/G | 0.2643 | likely_benign | 0.3027 | benign | -1.15 | Destabilizing | 0.038 | N | 0.494 | neutral | None | None | None | None | N |
| T/H | 0.2124 | likely_benign | 0.2322 | benign | -1.468 | Destabilizing | 0.864 | D | 0.561 | neutral | None | None | None | None | N |
| T/I | 0.1025 | likely_benign | 0.118 | benign | -0.276 | Destabilizing | 0.004 | N | 0.424 | neutral | N | 0.470941165 | None | None | N |
| T/K | 0.4082 | ambiguous | 0.4275 | ambiguous | -0.747 | Destabilizing | 0.055 | N | 0.473 | neutral | N | 0.512614409 | None | None | N |
| T/L | 0.0732 | likely_benign | 0.0787 | benign | -0.276 | Destabilizing | None | N | 0.335 | neutral | None | None | None | None | N |
| T/M | 0.0778 | likely_benign | 0.0797 | benign | 0.143 | Stabilizing | 0.003 | N | 0.423 | neutral | None | None | None | None | N |
| T/N | 0.1377 | likely_benign | 0.1462 | benign | -0.771 | Destabilizing | 0.072 | N | 0.455 | neutral | None | None | None | None | N |
| T/P | 0.5116 | ambiguous | 0.5416 | ambiguous | -0.449 | Destabilizing | 0.295 | N | 0.575 | neutral | N | 0.519190771 | None | None | N |
| T/Q | 0.2814 | likely_benign | 0.3076 | benign | -0.993 | Destabilizing | 0.214 | N | 0.579 | neutral | None | None | None | None | N |
| T/R | 0.3165 | likely_benign | 0.3363 | benign | -0.495 | Destabilizing | 0.171 | N | 0.578 | neutral | N | 0.477093231 | None | None | N |
| T/S | 0.0918 | likely_benign | 0.0998 | benign | -1.03 | Destabilizing | None | N | 0.243 | neutral | N | 0.482502146 | None | None | N |
| T/V | 0.0805 | likely_benign | 0.0898 | benign | -0.449 | Destabilizing | None | N | 0.209 | neutral | None | None | None | None | N |
| T/W | 0.4353 | ambiguous | 0.4899 | ambiguous | -0.928 | Destabilizing | 0.864 | D | 0.591 | neutral | None | None | None | None | N |
| T/Y | 0.1722 | likely_benign | 0.1883 | benign | -0.674 | Destabilizing | 0.356 | N | 0.553 | 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.