Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 6083 | 18472;18473;18474 | chr2:178730153;178730152;178730151 | chr2:179594880;179594879;179594878 |
| N2AB | 5766 | 17521;17522;17523 | chr2:178730153;178730152;178730151 | chr2:179594880;179594879;179594878 |
| N2A | 4839 | 14740;14741;14742 | chr2:178730153;178730152;178730151 | chr2:179594880;179594879;179594878 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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/T | None | None | 0.003 | N | 0.333 | 0.17 | 0.294561560033 | gnomAD-4.0.0 | 1.59216E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85927E-06 | 0 | 0 |
| I/V | rs374012753  |
-1.1 | 0.003 | N | 0.175 | 0.072 | None | gnomAD-2.1.1 | 2.02E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 9.3E-05 | 2.67E-05 | 0 |
| I/V | rs374012753 |
-1.1 | 0.003 | N | 0.175 | 0.072 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| I/V | rs374012753 |
-1.1 | 0.003 | N | 0.175 | 0.072 | None | gnomAD-4.0.0 | 1.7362E-05 | None | None | None | None | N | None | 1.33819E-05 | 0 | None | 0 | 0 | None | 9.39291E-05 | 0 | 1.6956E-05 | 0 | 1.6022E-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 | 0.2365 | likely_benign | 0.221 | benign | -2.175 | Highly Destabilizing | 0.176 | N | 0.459 | neutral | None | None | None | None | N |
| I/C | 0.636 | likely_pathogenic | 0.586 | pathogenic | -1.318 | Destabilizing | 0.981 | D | 0.591 | neutral | None | None | None | None | N |
| I/D | 0.5116 | ambiguous | 0.4939 | ambiguous | -2.364 | Highly Destabilizing | 0.704 | D | 0.594 | neutral | None | None | None | None | N |
| I/E | 0.4118 | ambiguous | 0.3927 | ambiguous | -2.125 | Highly Destabilizing | 0.704 | D | 0.589 | neutral | None | None | None | None | N |
| I/F | 0.1134 | likely_benign | 0.1143 | benign | -1.232 | Destabilizing | 0.784 | D | 0.539 | neutral | N | 0.443548608 | None | None | N |
| I/G | 0.546 | ambiguous | 0.5288 | ambiguous | -2.709 | Highly Destabilizing | 0.704 | D | 0.596 | neutral | None | None | None | None | N |
| I/H | 0.2717 | likely_benign | 0.2771 | benign | -2.283 | Highly Destabilizing | 0.981 | D | 0.647 | neutral | None | None | None | None | N |
| I/K | 0.2852 | likely_benign | 0.2774 | benign | -1.351 | Destabilizing | 0.329 | N | 0.563 | neutral | None | None | None | None | N |
| I/L | 0.1102 | likely_benign | 0.1087 | benign | -0.629 | Destabilizing | 0.139 | N | 0.406 | neutral | N | 0.436121203 | None | None | N |
| I/M | 0.1079 | likely_benign | 0.1024 | benign | -0.68 | Destabilizing | 0.927 | D | 0.549 | neutral | N | 0.441124378 | None | None | N |
| I/N | 0.1622 | likely_benign | 0.1578 | benign | -1.722 | Destabilizing | 0.642 | D | 0.589 | neutral | N | 0.456016473 | None | None | N |
| I/P | 0.9383 | likely_pathogenic | 0.934 | pathogenic | -1.126 | Destabilizing | 0.828 | D | 0.624 | neutral | None | None | None | None | N |
| I/Q | 0.3056 | likely_benign | 0.3026 | benign | -1.54 | Destabilizing | 0.893 | D | 0.63 | neutral | None | None | None | None | N |
| I/R | 0.1997 | likely_benign | 0.2011 | benign | -1.257 | Destabilizing | 0.007 | N | 0.526 | neutral | None | None | None | None | N |
| I/S | 0.1488 | likely_benign | 0.1457 | benign | -2.389 | Highly Destabilizing | 0.27 | N | 0.547 | neutral | N | 0.39556266 | None | None | N |
| I/T | 0.1083 | likely_benign | 0.0997 | benign | -2.007 | Highly Destabilizing | 0.003 | N | 0.333 | neutral | N | 0.329681598 | None | None | N |
| I/V | 0.0712 | likely_benign | 0.069 | benign | -1.126 | Destabilizing | 0.003 | N | 0.175 | neutral | N | 0.368877491 | None | None | N |
| I/W | 0.6642 | likely_pathogenic | 0.6629 | pathogenic | -1.633 | Destabilizing | 0.995 | D | 0.681 | prob.neutral | None | None | None | None | N |
| I/Y | 0.3275 | likely_benign | 0.3281 | benign | -1.303 | Destabilizing | 0.981 | D | 0.586 | 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.