Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17059 | 51400;51401;51402 | chr2:178610351;178610350;178610349 | chr2:179475078;179475077;179475076 |
| N2AB | 15418 | 46477;46478;46479 | chr2:178610351;178610350;178610349 | chr2:179475078;179475077;179475076 |
| N2A | 14491 | 43696;43697;43698 | chr2:178610351;178610350;178610349 | chr2:179475078;179475077;179475076 |
| N2B | 7994 | 24205;24206;24207 | chr2:178610351;178610350;178610349 | chr2:179475078;179475077;179475076 |
| Novex-1 | 8119 | 24580;24581;24582 | chr2:178610351;178610350;178610349 | chr2:179475078;179475077;179475076 |
| Novex-2 | 8186 | 24781;24782;24783 | chr2:178610351;178610350;178610349 | chr2:179475078;179475077;179475076 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/V | rs188395969  |
-0.756 | None | N | 0.091 | 0.087 | None | gnomAD-2.1.1 | 8.94E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.18961E-03 | None | 3.27E-05 | None | 0 | 0 | 1.40687E-04 |
| I/V | rs188395969 |
-0.756 | None | N | 0.091 | 0.087 | None | gnomAD-3.1.2 | 5.92E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.55461E-03 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/V | rs188395969 |
-0.756 | None | N | 0.091 | 0.087 | None | 1000 genomes | 3.99361E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 2E-03 | 0 | None | None | None | 0 | None |
| I/V | rs188395969 |
-0.756 | None | N | 0.091 | 0.087 | None | gnomAD-4.0.0 | 2.60427E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 8.50378E-04 | None | 0 | 0 | 8.48067E-07 | 1.09847E-05 | 3.20441E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.7306 | likely_pathogenic | 0.6213 | pathogenic | -1.399 | Destabilizing | 0.072 | N | 0.44 | neutral | None | None | None | None | N |
| I/C | 0.8169 | likely_pathogenic | 0.7825 | pathogenic | -1.157 | Destabilizing | 0.909 | D | 0.478 | neutral | None | None | None | None | N |
| I/D | 0.9766 | likely_pathogenic | 0.9593 | pathogenic | -1.745 | Destabilizing | 0.726 | D | 0.611 | neutral | None | None | None | None | N |
| I/E | 0.9373 | likely_pathogenic | 0.9005 | pathogenic | -1.791 | Destabilizing | 0.726 | D | 0.583 | neutral | None | None | None | None | N |
| I/F | 0.5583 | ambiguous | 0.491 | ambiguous | -1.477 | Destabilizing | 0.497 | N | 0.467 | neutral | D | 0.57674057 | None | None | N |
| I/G | 0.9368 | likely_pathogenic | 0.9007 | pathogenic | -1.644 | Destabilizing | 0.726 | D | 0.532 | neutral | None | None | None | None | N |
| I/H | 0.9394 | likely_pathogenic | 0.9007 | pathogenic | -1.077 | Destabilizing | 0.968 | D | 0.603 | neutral | None | None | None | None | N |
| I/K | 0.8989 | likely_pathogenic | 0.8146 | pathogenic | -0.911 | Destabilizing | 0.726 | D | 0.589 | neutral | None | None | None | None | N |
| I/L | 0.2595 | likely_benign | 0.2423 | benign | -0.815 | Destabilizing | 0.025 | N | 0.201 | neutral | N | 0.48455534 | None | None | N |
| I/M | 0.2491 | likely_benign | 0.2276 | benign | -0.556 | Destabilizing | 0.497 | N | 0.518 | neutral | D | 0.543475672 | None | None | N |
| I/N | 0.8035 | likely_pathogenic | 0.7029 | pathogenic | -0.82 | Destabilizing | 0.859 | D | 0.601 | neutral | D | 0.564461011 | None | None | N |
| I/P | 0.9159 | likely_pathogenic | 0.8683 | pathogenic | -0.981 | Destabilizing | 0.726 | D | 0.607 | neutral | None | None | None | None | N |
| I/Q | 0.898 | likely_pathogenic | 0.8456 | pathogenic | -1.132 | Destabilizing | 0.89 | D | 0.608 | neutral | None | None | None | None | N |
| I/R | 0.8771 | likely_pathogenic | 0.7749 | pathogenic | -0.332 | Destabilizing | 0.726 | D | 0.603 | neutral | None | None | None | None | N |
| I/S | 0.7742 | likely_pathogenic | 0.6646 | pathogenic | -1.276 | Destabilizing | 0.497 | N | 0.493 | neutral | N | 0.470564013 | None | None | N |
| I/T | 0.484 | ambiguous | 0.3836 | ambiguous | -1.218 | Destabilizing | 0.124 | N | 0.415 | neutral | N | 0.483498247 | None | None | N |
| I/V | 0.064 | likely_benign | 0.061 | benign | -0.981 | Destabilizing | None | N | 0.091 | neutral | N | 0.446509459 | None | None | N |
| I/W | 0.9763 | likely_pathogenic | 0.9683 | pathogenic | -1.567 | Destabilizing | 0.968 | D | 0.701 | prob.neutral | None | None | None | None | N |
| I/Y | 0.8918 | likely_pathogenic | 0.847 | pathogenic | -1.241 | Destabilizing | 0.726 | D | 0.521 | 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.