Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29217 | 87874;87875;87876 | chr2:178557705;178557704;178557703 | chr2:179422432;179422431;179422430 |
| N2AB | 27576 | 82951;82952;82953 | chr2:178557705;178557704;178557703 | chr2:179422432;179422431;179422430 |
| N2A | 26649 | 80170;80171;80172 | chr2:178557705;178557704;178557703 | chr2:179422432;179422431;179422430 |
| N2B | 20152 | 60679;60680;60681 | chr2:178557705;178557704;178557703 | chr2:179422432;179422431;179422430 |
| Novex-1 | 20277 | 61054;61055;61056 | chr2:178557705;178557704;178557703 | chr2:179422432;179422431;179422430 |
| Novex-2 | 20344 | 61255;61256;61257 | chr2:178557705;178557704;178557703 | chr2:179422432;179422431;179422430 |
| 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/C | rs398124459  |
None | 0.999 | N | 0.489 | 0.486 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 2.07297E-04 | 0 |
| R/C | rs398124459 |
None | 0.999 | N | 0.489 | 0.486 | None | gnomAD-4.0.0 | 9.91457E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 6.6839E-05 | None | 0 | 0 | 6.78055E-06 | 3.2941E-05 | 3.20184E-05 |
| R/H | rs749606240 |
-1.076 | 0.996 | N | 0.364 | 0.336 | 0.373173300195 | gnomAD-2.1.1 | 3.92E-05 | None | None | None | None | I | None | 1.23977E-04 | 0 | None | 0 | 5.12E-05 | None | 0 | None | 4E-05 | 3.9E-05 | 1.40292E-04 |
| R/H | rs749606240 |
-1.076 | 0.996 | N | 0.364 | 0.336 | 0.373173300195 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 7.24E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/H | rs749606240 |
-1.076 | 0.996 | N | 0.364 | 0.336 | 0.373173300195 | gnomAD-4.0.0 | 2.29266E-05 | None | None | None | None | I | None | 6.67289E-05 | 0 | None | 0 | 2.22787E-05 | None | 0 | 4.93583E-04 | 1.94938E-05 | 1.09803E-05 | 6.40369E-05 |
| R/S | None | None | 0.846 | N | 0.519 | 0.314 | 0.266843984389 | gnomAD-4.0.0 | 6.84167E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99423E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9655 | likely_pathogenic | 0.9786 | pathogenic | -0.03 | Destabilizing | 0.373 | N | 0.467 | neutral | None | None | None | None | I |
| R/C | 0.703 | likely_pathogenic | 0.8398 | pathogenic | -0.328 | Destabilizing | 0.999 | D | 0.489 | neutral | N | 0.49467728 | None | None | I |
| R/D | 0.9913 | likely_pathogenic | 0.9937 | pathogenic | -0.204 | Destabilizing | 0.91 | D | 0.509 | neutral | None | None | None | None | I |
| R/E | 0.9659 | likely_pathogenic | 0.9761 | pathogenic | -0.146 | Destabilizing | 0.742 | D | 0.401 | neutral | None | None | None | None | I |
| R/F | 0.9845 | likely_pathogenic | 0.9886 | pathogenic | -0.36 | Destabilizing | 0.835 | D | 0.494 | neutral | None | None | None | None | I |
| R/G | 0.955 | likely_pathogenic | 0.9739 | pathogenic | -0.191 | Destabilizing | 0.017 | N | 0.301 | neutral | N | 0.463181441 | None | None | I |
| R/H | 0.5775 | likely_pathogenic | 0.6738 | pathogenic | -0.789 | Destabilizing | 0.996 | D | 0.364 | neutral | N | 0.480180649 | None | None | I |
| R/I | 0.8895 | likely_pathogenic | 0.9216 | pathogenic | 0.349 | Stabilizing | 0.953 | D | 0.495 | neutral | None | None | None | None | I |
| R/K | 0.4498 | ambiguous | 0.516 | ambiguous | -0.177 | Destabilizing | 0.037 | N | 0.238 | neutral | None | None | None | None | I |
| R/L | 0.8799 | likely_pathogenic | 0.9135 | pathogenic | 0.349 | Stabilizing | 0.846 | D | 0.571 | neutral | N | 0.515267925 | None | None | I |
| R/M | 0.9393 | likely_pathogenic | 0.9605 | pathogenic | -0.126 | Destabilizing | 0.996 | D | 0.428 | neutral | None | None | None | None | I |
| R/N | 0.9791 | likely_pathogenic | 0.9861 | pathogenic | -0.125 | Destabilizing | 0.742 | D | 0.389 | neutral | None | None | None | None | I |
| R/P | 0.9669 | likely_pathogenic | 0.9785 | pathogenic | 0.242 | Stabilizing | 0.992 | D | 0.529 | neutral | N | 0.510150107 | None | None | I |
| R/Q | 0.5799 | likely_pathogenic | 0.6846 | pathogenic | -0.145 | Destabilizing | 0.91 | D | 0.398 | neutral | None | None | None | None | I |
| R/S | 0.9772 | likely_pathogenic | 0.9851 | pathogenic | -0.366 | Destabilizing | 0.846 | D | 0.519 | neutral | N | 0.471765077 | None | None | I |
| R/T | 0.9582 | likely_pathogenic | 0.9698 | pathogenic | -0.182 | Destabilizing | 0.854 | D | 0.501 | neutral | None | None | None | None | I |
| R/V | 0.9355 | likely_pathogenic | 0.9544 | pathogenic | 0.242 | Stabilizing | 0.953 | D | 0.507 | neutral | None | None | None | None | I |
| R/W | 0.8477 | likely_pathogenic | 0.8986 | pathogenic | -0.522 | Destabilizing | 0.02 | N | 0.531 | neutral | None | None | None | None | I |
| R/Y | 0.9271 | likely_pathogenic | 0.9543 | pathogenic | -0.096 | Destabilizing | 0.835 | D | 0.521 | neutral | None | None | None | None | I |
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.