Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17118 | 51577;51578;51579 | chr2:178610174;178610173;178610172 | chr2:179474901;179474900;179474899 |
| N2AB | 15477 | 46654;46655;46656 | chr2:178610174;178610173;178610172 | chr2:179474901;179474900;179474899 |
| N2A | 14550 | 43873;43874;43875 | chr2:178610174;178610173;178610172 | chr2:179474901;179474900;179474899 |
| N2B | 8053 | 24382;24383;24384 | chr2:178610174;178610173;178610172 | chr2:179474901;179474900;179474899 |
| Novex-1 | 8178 | 24757;24758;24759 | chr2:178610174;178610173;178610172 | chr2:179474901;179474900;179474899 |
| Novex-2 | 8245 | 24958;24959;24960 | chr2:178610174;178610173;178610172 | chr2:179474901;179474900;179474899 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/L | rs1161061741  |
-1.903 | 0.454 | N | 0.541 | 0.317 | 0.524843318063 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.59E-05 | None | 0 | None | 0 | 0 | 0 |
| F/L | rs1161061741 |
-1.903 | 0.454 | N | 0.541 | 0.317 | 0.524843318063 | gnomAD-4.0.0 | 6.84493E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.52449E-05 | None | 0 | 0 | 0 | 0 | 0 |
| F/V | None | None | 0.801 | N | 0.577 | 0.357 | 0.627942663015 | gnomAD-4.0.0 | 6.84493E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99785E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.9024 | likely_pathogenic | 0.9128 | pathogenic | -2.733 | Highly Destabilizing | 0.842 | D | 0.601 | neutral | None | None | None | None | N |
| F/C | 0.5568 | ambiguous | 0.6223 | pathogenic | -1.19 | Destabilizing | 0.997 | D | 0.63 | neutral | N | 0.4752481 | None | None | N |
| F/D | 0.9648 | likely_pathogenic | 0.9662 | pathogenic | -3.071 | Highly Destabilizing | 0.991 | D | 0.629 | neutral | None | None | None | None | N |
| F/E | 0.9721 | likely_pathogenic | 0.9724 | pathogenic | -2.869 | Highly Destabilizing | 0.974 | D | 0.627 | neutral | None | None | None | None | N |
| F/G | 0.9628 | likely_pathogenic | 0.9639 | pathogenic | -3.143 | Highly Destabilizing | 0.915 | D | 0.559 | neutral | None | None | None | None | N |
| F/H | 0.6181 | likely_pathogenic | 0.6291 | pathogenic | -1.744 | Destabilizing | 0.949 | D | 0.577 | neutral | None | None | None | None | N |
| F/I | 0.542 | ambiguous | 0.6695 | pathogenic | -1.386 | Destabilizing | 0.801 | D | 0.559 | neutral | N | 0.417719949 | None | None | N |
| F/K | 0.9669 | likely_pathogenic | 0.9695 | pathogenic | -1.741 | Destabilizing | 0.974 | D | 0.627 | neutral | None | None | None | None | N |
| F/L | 0.9262 | likely_pathogenic | 0.9519 | pathogenic | -1.386 | Destabilizing | 0.454 | N | 0.541 | neutral | N | 0.432091968 | None | None | N |
| F/M | 0.8053 | likely_pathogenic | 0.8466 | pathogenic | -0.934 | Destabilizing | 0.991 | D | 0.548 | neutral | None | None | None | None | N |
| F/N | 0.8057 | likely_pathogenic | 0.8303 | pathogenic | -2.212 | Highly Destabilizing | 0.974 | D | 0.644 | neutral | None | None | None | None | N |
| F/P | 0.9994 | likely_pathogenic | 0.9992 | pathogenic | -1.847 | Destabilizing | 0.991 | D | 0.654 | neutral | None | None | None | None | N |
| F/Q | 0.9088 | likely_pathogenic | 0.9091 | pathogenic | -2.17 | Highly Destabilizing | 0.991 | D | 0.642 | neutral | None | None | None | None | N |
| F/R | 0.908 | likely_pathogenic | 0.9118 | pathogenic | -1.319 | Destabilizing | 0.974 | D | 0.649 | neutral | None | None | None | None | N |
| F/S | 0.7767 | likely_pathogenic | 0.8161 | pathogenic | -2.757 | Highly Destabilizing | 0.891 | D | 0.552 | neutral | N | 0.429819667 | None | None | N |
| F/T | 0.8521 | likely_pathogenic | 0.8732 | pathogenic | -2.456 | Highly Destabilizing | 0.915 | D | 0.579 | neutral | None | None | None | None | N |
| F/V | 0.5618 | ambiguous | 0.6601 | pathogenic | -1.847 | Destabilizing | 0.801 | D | 0.577 | neutral | N | 0.432398613 | None | None | N |
| F/W | 0.6482 | likely_pathogenic | 0.639 | pathogenic | -0.417 | Destabilizing | 0.974 | D | 0.575 | neutral | None | None | None | None | N |
| F/Y | 0.0903 | likely_benign | 0.0865 | benign | -0.78 | Destabilizing | 0.002 | N | 0.225 | neutral | N | 0.401558417 | 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.