Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21606 | 65041;65042;65043 | chr2:178584825;178584824;178584823 | chr2:179449552;179449551;179449550 |
| N2AB | 19965 | 60118;60119;60120 | chr2:178584825;178584824;178584823 | chr2:179449552;179449551;179449550 |
| N2A | 19038 | 57337;57338;57339 | chr2:178584825;178584824;178584823 | chr2:179449552;179449551;179449550 |
| N2B | 12541 | 37846;37847;37848 | chr2:178584825;178584824;178584823 | chr2:179449552;179449551;179449550 |
| Novex-1 | 12666 | 38221;38222;38223 | chr2:178584825;178584824;178584823 | chr2:179449552;179449551;179449550 |
| Novex-2 | 12733 | 38422;38423;38424 | chr2:178584825;178584824;178584823 | chr2:179449552;179449551;179449550 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/H | rs751046367  |
-0.072 | 0.948 | N | 0.637 | 0.344 | 0.235038932564 | gnomAD-2.1.1 | 7.65E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 9.8E-05 | None | 0 | 1.42592E-04 | 0 |
| D/H | rs751046367 |
-0.072 | 0.948 | N | 0.637 | 0.344 | 0.235038932564 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 2.07297E-04 | 0 |
| D/H | rs751046367 |
-0.072 | 0.948 | N | 0.637 | 0.344 | 0.235038932564 | gnomAD-4.0.0 | 2.60341E-05 | None | None | None | None | I | None | 1.33561E-05 | 0 | None | 0 | 0 | None | 0 | 8.22639E-04 | 2.28904E-05 | 5.49064E-05 | 6.40697E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.2755 | likely_benign | 0.3437 | ambiguous | -0.572 | Destabilizing | 0.83 | D | 0.566 | neutral | N | 0.464263102 | None | None | I |
| D/C | 0.6865 | likely_pathogenic | 0.7714 | pathogenic | -0.1 | Destabilizing | 0.993 | D | 0.744 | deleterious | None | None | None | None | I |
| D/E | 0.2196 | likely_benign | 0.2473 | benign | -0.497 | Destabilizing | 0.41 | N | 0.469 | neutral | N | 0.454102036 | None | None | I |
| D/F | 0.6595 | likely_pathogenic | 0.7294 | pathogenic | -0.474 | Destabilizing | 0.993 | D | 0.721 | prob.delet. | None | None | None | None | I |
| D/G | 0.3324 | likely_benign | 0.4093 | ambiguous | -0.801 | Destabilizing | 0.41 | N | 0.543 | neutral | N | 0.43089989 | None | None | I |
| D/H | 0.3828 | ambiguous | 0.4959 | ambiguous | -0.521 | Destabilizing | 0.948 | D | 0.637 | neutral | N | 0.509843463 | None | None | I |
| D/I | 0.346 | ambiguous | 0.4212 | ambiguous | -0.001 | Destabilizing | 0.929 | D | 0.723 | prob.delet. | None | None | None | None | I |
| D/K | 0.4977 | ambiguous | 0.6066 | pathogenic | -0.093 | Destabilizing | 0.764 | D | 0.576 | neutral | None | None | None | None | I |
| D/L | 0.4469 | ambiguous | 0.5272 | ambiguous | -0.001 | Destabilizing | 0.866 | D | 0.695 | prob.neutral | None | None | None | None | I |
| D/M | 0.6422 | likely_pathogenic | 0.7132 | pathogenic | 0.316 | Stabilizing | 0.993 | D | 0.729 | prob.delet. | None | None | None | None | I |
| D/N | 0.1106 | likely_benign | 0.1444 | benign | -0.338 | Destabilizing | 0.01 | N | 0.389 | neutral | N | 0.469919638 | None | None | I |
| D/P | 0.8491 | likely_pathogenic | 0.9074 | pathogenic | -0.169 | Destabilizing | 0.929 | D | 0.609 | neutral | None | None | None | None | I |
| D/Q | 0.4039 | ambiguous | 0.5122 | ambiguous | -0.298 | Destabilizing | 0.866 | D | 0.593 | neutral | None | None | None | None | I |
| D/R | 0.5275 | ambiguous | 0.6401 | pathogenic | 0.074 | Stabilizing | 0.866 | D | 0.659 | neutral | None | None | None | None | I |
| D/S | 0.1856 | likely_benign | 0.2438 | benign | -0.483 | Destabilizing | 0.48 | N | 0.546 | neutral | None | None | None | None | I |
| D/T | 0.3125 | likely_benign | 0.3947 | ambiguous | -0.309 | Destabilizing | 0.764 | D | 0.581 | neutral | None | None | None | None | I |
| D/V | 0.2384 | likely_benign | 0.2853 | benign | -0.169 | Destabilizing | 0.908 | D | 0.698 | prob.neutral | N | 0.450045798 | None | None | I |
| D/W | 0.912 | likely_pathogenic | 0.9428 | pathogenic | -0.311 | Destabilizing | 0.993 | D | 0.742 | deleterious | None | None | None | None | I |
| D/Y | 0.3053 | likely_benign | 0.3759 | ambiguous | -0.249 | Destabilizing | 0.991 | D | 0.717 | prob.delet. | N | 0.475473842 | 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.