Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19690 | 59293;59294;59295 | chr2:178593051;178593050;178593049 | chr2:179457778;179457777;179457776 |
| N2AB | 18049 | 54370;54371;54372 | chr2:178593051;178593050;178593049 | chr2:179457778;179457777;179457776 |
| N2A | 17122 | 51589;51590;51591 | chr2:178593051;178593050;178593049 | chr2:179457778;179457777;179457776 |
| N2B | 10625 | 32098;32099;32100 | chr2:178593051;178593050;178593049 | chr2:179457778;179457777;179457776 |
| Novex-1 | 10750 | 32473;32474;32475 | chr2:178593051;178593050;178593049 | chr2:179457778;179457777;179457776 |
| Novex-2 | 10817 | 32674;32675;32676 | chr2:178593051;178593050;178593049 | chr2:179457778;179457777;179457776 |
| 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/L | rs1305679009  |
-0.244 | 0.012 | N | 0.203 | 0.055 | 0.275215494804 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| I/L | rs1305679009 |
-0.244 | 0.012 | N | 0.203 | 0.055 | 0.275215494804 | gnomAD-4.0.0 | 6.15944E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.09645E-06 | 0 | 0 |
| I/T | rs1359437797 |
-0.365 | 0.002 | N | 0.225 | 0.158 | 0.476445137733 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 1.14732E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs1359437797 |
-0.365 | 0.002 | N | 0.225 | 0.158 | 0.476445137733 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 9.65E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs1359437797 |
-0.365 | 0.002 | N | 0.225 | 0.158 | 0.476445137733 | gnomAD-4.0.0 | 3.71918E-06 | None | None | None | None | N | None | 5.34131E-05 | 0 | None | 0 | 2.23474E-05 | None | 0 | 0 | 0 | 0 | 1.60138E-05 |
| I/V | rs1305679009 |
-0.287 | None | N | 0.085 | 0.113 | 0.238705975628 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.61E-05 | None | 0 | None | 0 | 0 | 0 |
| I/V | rs1305679009 |
-0.287 | None | N | 0.085 | 0.113 | 0.238705975628 | gnomAD-4.0.0 | 6.84382E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.52615E-05 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.1657 | likely_benign | 0.1198 | benign | -0.759 | Destabilizing | 0.035 | N | 0.4 | neutral | None | None | None | None | N |
| I/C | 0.6022 | likely_pathogenic | 0.52 | ambiguous | -0.538 | Destabilizing | 0.824 | D | 0.417 | neutral | None | None | None | None | N |
| I/D | 0.6131 | likely_pathogenic | 0.4442 | ambiguous | -0.282 | Destabilizing | 0.555 | D | 0.475 | neutral | None | None | None | None | N |
| I/E | 0.3993 | ambiguous | 0.2939 | benign | -0.383 | Destabilizing | 0.555 | D | 0.459 | neutral | None | None | None | None | N |
| I/F | 0.168 | likely_benign | 0.128 | benign | -0.797 | Destabilizing | 0.38 | N | 0.399 | neutral | None | None | None | None | N |
| I/G | 0.4461 | ambiguous | 0.312 | benign | -0.928 | Destabilizing | 0.262 | N | 0.46 | neutral | None | None | None | None | N |
| I/H | 0.4331 | ambiguous | 0.3379 | benign | -0.204 | Destabilizing | 0.935 | D | 0.479 | neutral | None | None | None | None | N |
| I/K | 0.2296 | likely_benign | 0.1772 | benign | -0.336 | Destabilizing | 0.484 | N | 0.455 | neutral | N | 0.455083471 | None | None | N |
| I/L | 0.1261 | likely_benign | 0.103 | benign | -0.436 | Destabilizing | 0.012 | N | 0.203 | neutral | N | 0.440596808 | None | None | N |
| I/M | 0.0958 | likely_benign | 0.0818 | benign | -0.349 | Destabilizing | 0.317 | N | 0.427 | neutral | N | 0.503416136 | None | None | N |
| I/N | 0.2372 | likely_benign | 0.1764 | benign | -0.085 | Destabilizing | 0.555 | D | 0.497 | neutral | None | None | None | None | N |
| I/P | 0.8166 | likely_pathogenic | 0.6768 | pathogenic | -0.51 | Destabilizing | 0.791 | D | 0.494 | neutral | None | None | None | None | N |
| I/Q | 0.2939 | likely_benign | 0.2294 | benign | -0.364 | Destabilizing | 0.791 | D | 0.496 | neutral | None | None | None | None | N |
| I/R | 0.2006 | likely_benign | 0.1458 | benign | 0.269 | Stabilizing | 0.484 | N | 0.5 | neutral | N | 0.508840598 | None | None | N |
| I/S | 0.1773 | likely_benign | 0.1382 | benign | -0.546 | Destabilizing | 0.081 | N | 0.43 | neutral | None | None | None | None | N |
| I/T | 0.0816 | likely_benign | 0.0663 | benign | -0.542 | Destabilizing | 0.002 | N | 0.225 | neutral | N | 0.445885198 | None | None | N |
| I/V | 0.0651 | likely_benign | 0.056 | benign | -0.51 | Destabilizing | None | N | 0.085 | neutral | N | 0.419144101 | None | None | N |
| I/W | 0.7134 | likely_pathogenic | 0.6178 | pathogenic | -0.787 | Destabilizing | 0.935 | D | 0.572 | neutral | None | None | None | None | N |
| I/Y | 0.5189 | ambiguous | 0.4102 | ambiguous | -0.532 | Destabilizing | 0.555 | D | 0.448 | 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.