Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31422 | 94489;94490;94491 | chr2:178547261;178547260;178547259 | chr2:179411988;179411987;179411986 |
| N2AB | 29781 | 89566;89567;89568 | chr2:178547261;178547260;178547259 | chr2:179411988;179411987;179411986 |
| N2A | 28854 | 86785;86786;86787 | chr2:178547261;178547260;178547259 | chr2:179411988;179411987;179411986 |
| N2B | 22357 | 67294;67295;67296 | chr2:178547261;178547260;178547259 | chr2:179411988;179411987;179411986 |
| Novex-1 | 22482 | 67669;67670;67671 | chr2:178547261;178547260;178547259 | chr2:179411988;179411987;179411986 |
| Novex-2 | 22549 | 67870;67871;67872 | chr2:178547261;178547260;178547259 | chr2:179411988;179411987;179411986 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/P | rs755395347  |
-0.717 | 0.991 | N | 0.673 | 0.293 | 0.435590266561 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| A/P | rs755395347 |
-0.717 | 0.991 | N | 0.673 | 0.293 | 0.435590266561 | gnomAD-4.0.0 | 1.59183E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85943E-06 | 0 | 0 |
| A/V | None | None | 0.969 | N | 0.617 | 0.255 | 0.458101713262 | gnomAD-4.0.0 | 1.59161E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43287E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.5113 | ambiguous | 0.4249 | ambiguous | -1.089 | Destabilizing | 0.999 | D | 0.656 | neutral | None | None | None | None | N |
| A/D | 0.6728 | likely_pathogenic | 0.6633 | pathogenic | -1.987 | Destabilizing | 0.964 | D | 0.613 | neutral | N | 0.454584826 | None | None | N |
| A/E | 0.528 | ambiguous | 0.5337 | ambiguous | -2.095 | Highly Destabilizing | 0.986 | D | 0.643 | neutral | None | None | None | None | N |
| A/F | 0.6268 | likely_pathogenic | 0.5796 | pathogenic | -1.433 | Destabilizing | 0.998 | D | 0.673 | neutral | None | None | None | None | N |
| A/G | 0.1745 | likely_benign | 0.1614 | benign | -0.957 | Destabilizing | 0.885 | D | 0.505 | neutral | N | 0.454931542 | None | None | N |
| A/H | 0.689 | likely_pathogenic | 0.6356 | pathogenic | -0.92 | Destabilizing | 0.998 | D | 0.657 | neutral | None | None | None | None | N |
| A/I | 0.4744 | ambiguous | 0.4329 | ambiguous | -0.675 | Destabilizing | 0.993 | D | 0.673 | neutral | None | None | None | None | N |
| A/K | 0.7103 | likely_pathogenic | 0.6994 | pathogenic | -1.061 | Destabilizing | 0.986 | D | 0.645 | neutral | None | None | None | None | N |
| A/L | 0.3799 | ambiguous | 0.3405 | ambiguous | -0.675 | Destabilizing | 0.976 | D | 0.617 | neutral | None | None | None | None | N |
| A/M | 0.4014 | ambiguous | 0.3798 | ambiguous | -0.425 | Destabilizing | 0.999 | D | 0.649 | neutral | None | None | None | None | N |
| A/N | 0.4246 | ambiguous | 0.3844 | ambiguous | -0.93 | Destabilizing | 0.128 | N | 0.461 | neutral | None | None | None | None | N |
| A/P | 0.4017 | ambiguous | 0.3862 | ambiguous | -0.695 | Destabilizing | 0.991 | D | 0.673 | neutral | N | 0.476594894 | None | None | N |
| A/Q | 0.5012 | ambiguous | 0.4658 | ambiguous | -1.31 | Destabilizing | 0.993 | D | 0.676 | prob.neutral | None | None | None | None | N |
| A/R | 0.6503 | likely_pathogenic | 0.6376 | pathogenic | -0.502 | Destabilizing | 0.986 | D | 0.671 | neutral | None | None | None | None | N |
| A/S | 0.0982 | likely_benign | 0.0908 | benign | -1.069 | Destabilizing | 0.374 | N | 0.41 | neutral | N | 0.423259054 | None | None | N |
| A/T | 0.156 | likely_benign | 0.1428 | benign | -1.119 | Destabilizing | 0.885 | D | 0.549 | neutral | N | 0.49831696 | None | None | N |
| A/V | 0.2387 | likely_benign | 0.2186 | benign | -0.695 | Destabilizing | 0.969 | D | 0.617 | neutral | N | 0.470282829 | None | None | N |
| A/W | 0.9082 | likely_pathogenic | 0.8763 | pathogenic | -1.607 | Destabilizing | 0.999 | D | 0.661 | neutral | None | None | None | None | N |
| A/Y | 0.7083 | likely_pathogenic | 0.6579 | pathogenic | -1.234 | Destabilizing | 0.998 | D | 0.672 | 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.