Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21654 | 65185;65186;65187 | chr2:178584681;178584680;178584679 | chr2:179449408;179449407;179449406 |
| N2AB | 20013 | 60262;60263;60264 | chr2:178584681;178584680;178584679 | chr2:179449408;179449407;179449406 |
| N2A | 19086 | 57481;57482;57483 | chr2:178584681;178584680;178584679 | chr2:179449408;179449407;179449406 |
| N2B | 12589 | 37990;37991;37992 | chr2:178584681;178584680;178584679 | chr2:179449408;179449407;179449406 |
| Novex-1 | 12714 | 38365;38366;38367 | chr2:178584681;178584680;178584679 | chr2:179449408;179449407;179449406 |
| Novex-2 | 12781 | 38566;38567;38568 | chr2:178584681;178584680;178584679 | chr2:179449408;179449407;179449406 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Q/R | rs555785232  |
0.342 | None | N | 0.085 | 0.083 | 0.12205267543 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 6.47E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| Q/R | rs555785232 |
0.342 | None | N | 0.085 | 0.083 | 0.12205267543 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| Q/R | rs555785232 |
0.342 | None | N | 0.085 | 0.083 | 0.12205267543 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| Q/R | rs555785232 |
0.342 | None | N | 0.085 | 0.083 | 0.12205267543 | gnomAD-4.0.0 | 2.02989E-06 | None | None | None | None | I | None | 1.7441E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.20498E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Q/A | 0.1642 | likely_benign | 0.1629 | benign | -0.337 | Destabilizing | 0.001 | N | 0.317 | neutral | None | None | None | None | I |
| Q/C | 0.4306 | ambiguous | 0.3896 | ambiguous | 0.073 | Stabilizing | 0.314 | N | 0.311 | neutral | None | None | None | None | I |
| Q/D | 0.4198 | ambiguous | 0.3609 | ambiguous | 0.267 | Stabilizing | 0.009 | N | 0.276 | neutral | None | None | None | None | I |
| Q/E | 0.0897 | likely_benign | 0.0791 | benign | 0.264 | Stabilizing | 0.001 | N | 0.253 | neutral | N | 0.446250557 | None | None | I |
| Q/F | 0.6686 | likely_pathogenic | 0.6456 | pathogenic | -0.444 | Destabilizing | 0.314 | N | 0.548 | neutral | None | None | None | None | I |
| Q/G | 0.2565 | likely_benign | 0.2434 | benign | -0.55 | Destabilizing | 0.004 | N | 0.412 | neutral | None | None | None | None | I |
| Q/H | 0.1932 | likely_benign | 0.1705 | benign | -0.318 | Destabilizing | 0.102 | N | 0.359 | neutral | N | 0.48026713 | None | None | I |
| Q/I | 0.3567 | ambiguous | 0.3355 | benign | 0.141 | Stabilizing | 0.041 | N | 0.635 | neutral | None | None | None | None | I |
| Q/K | 0.0649 | likely_benign | 0.0638 | benign | 0.09 | Stabilizing | None | N | 0.097 | neutral | N | 0.342141968 | None | None | I |
| Q/L | 0.1442 | likely_benign | 0.1346 | benign | 0.141 | Stabilizing | 0.003 | N | 0.412 | neutral | N | 0.460294503 | None | None | I |
| Q/M | 0.3 | likely_benign | 0.2823 | benign | 0.319 | Stabilizing | 0.314 | N | 0.337 | neutral | None | None | None | None | I |
| Q/N | 0.2634 | likely_benign | 0.2429 | benign | -0.316 | Destabilizing | 0.009 | N | 0.257 | neutral | None | None | None | None | I |
| Q/P | 0.6542 | likely_pathogenic | 0.629 | pathogenic | 0.011 | Stabilizing | 0.013 | N | 0.41 | neutral | N | 0.448482786 | None | None | I |
| Q/R | 0.075 | likely_benign | 0.0731 | benign | 0.236 | Stabilizing | None | N | 0.085 | neutral | N | 0.386911465 | None | None | I |
| Q/S | 0.166 | likely_benign | 0.1728 | benign | -0.365 | Destabilizing | 0.002 | N | 0.253 | neutral | None | None | None | None | I |
| Q/T | 0.1409 | likely_benign | 0.1391 | benign | -0.195 | Destabilizing | 0.009 | N | 0.354 | neutral | None | None | None | None | I |
| Q/V | 0.2071 | likely_benign | 0.1947 | benign | 0.011 | Stabilizing | 0.009 | N | 0.421 | neutral | None | None | None | None | I |
| Q/W | 0.5961 | likely_pathogenic | 0.5668 | pathogenic | -0.378 | Destabilizing | 0.633 | D | 0.337 | neutral | None | None | None | None | I |
| Q/Y | 0.4646 | ambiguous | 0.4286 | ambiguous | -0.137 | Destabilizing | 0.041 | N | 0.51 | 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.