Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17173 | 51742;51743;51744 | chr2:178609906;178609905;178609904 | chr2:179474633;179474632;179474631 |
| N2AB | 15532 | 46819;46820;46821 | chr2:178609906;178609905;178609904 | chr2:179474633;179474632;179474631 |
| N2A | 14605 | 44038;44039;44040 | chr2:178609906;178609905;178609904 | chr2:179474633;179474632;179474631 |
| N2B | 8108 | 24547;24548;24549 | chr2:178609906;178609905;178609904 | chr2:179474633;179474632;179474631 |
| Novex-1 | 8233 | 24922;24923;24924 | chr2:178609906;178609905;178609904 | chr2:179474633;179474632;179474631 |
| Novex-2 | 8300 | 25123;25124;25125 | chr2:178609906;178609905;178609904 | chr2:179474633;179474632;179474631 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/C | rs748656984  |
0.308 | 0.997 | N | 0.655 | 0.297 | 0.451599300725 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 6.54E-05 | None | 0 | 0 | 0 |
| Y/C | rs748656984 |
0.308 | 0.997 | N | 0.655 | 0.297 | 0.451599300725 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| Y/C | rs748656984 |
0.308 | 0.997 | N | 0.655 | 0.297 | 0.451599300725 | gnomAD-4.0.0 | 7.69422E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.39582E-06 | 6.70367E-05 | 0 |
| Y/H | None | None | 0.99 | N | 0.547 | 0.302 | 0.315314060047 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.8189 | likely_pathogenic | 0.7169 | pathogenic | -0.557 | Destabilizing | 0.86 | D | 0.527 | neutral | None | None | None | None | I |
| Y/C | 0.3268 | likely_benign | 0.221 | benign | 0.275 | Stabilizing | 0.997 | D | 0.655 | neutral | N | 0.468869888 | None | None | I |
| Y/D | 0.7605 | likely_pathogenic | 0.583 | pathogenic | 0.982 | Stabilizing | 0.99 | D | 0.685 | prob.neutral | N | 0.381948363 | None | None | I |
| Y/E | 0.9201 | likely_pathogenic | 0.8437 | pathogenic | 0.947 | Stabilizing | 0.993 | D | 0.652 | neutral | None | None | None | None | I |
| Y/F | 0.1169 | likely_benign | 0.101 | benign | -0.362 | Destabilizing | 0.014 | N | 0.211 | neutral | N | 0.471954291 | None | None | I |
| Y/G | 0.7445 | likely_pathogenic | 0.6342 | pathogenic | -0.731 | Destabilizing | 0.978 | D | 0.669 | neutral | None | None | None | None | I |
| Y/H | 0.2909 | likely_benign | 0.1984 | benign | 0.26 | Stabilizing | 0.99 | D | 0.547 | neutral | N | 0.463969526 | None | None | I |
| Y/I | 0.8332 | likely_pathogenic | 0.7238 | pathogenic | -0.138 | Destabilizing | 0.915 | D | 0.541 | neutral | None | None | None | None | I |
| Y/K | 0.8878 | likely_pathogenic | 0.8163 | pathogenic | 0.41 | Stabilizing | 0.978 | D | 0.647 | neutral | None | None | None | None | I |
| Y/L | 0.7503 | likely_pathogenic | 0.6418 | pathogenic | -0.138 | Destabilizing | 0.754 | D | 0.568 | neutral | None | None | None | None | I |
| Y/M | 0.8196 | likely_pathogenic | 0.7421 | pathogenic | 0.086 | Stabilizing | 0.994 | D | 0.563 | neutral | None | None | None | None | I |
| Y/N | 0.2846 | likely_benign | 0.1795 | benign | 0.299 | Stabilizing | 0.99 | D | 0.653 | neutral | N | 0.440380591 | None | None | I |
| Y/P | 0.9822 | likely_pathogenic | 0.9759 | pathogenic | -0.257 | Destabilizing | 0.993 | D | 0.679 | prob.neutral | None | None | None | None | I |
| Y/Q | 0.778 | likely_pathogenic | 0.6576 | pathogenic | 0.288 | Stabilizing | 0.993 | D | 0.586 | neutral | None | None | None | None | I |
| Y/R | 0.7116 | likely_pathogenic | 0.6099 | pathogenic | 0.688 | Stabilizing | 0.978 | D | 0.653 | neutral | None | None | None | None | I |
| Y/S | 0.4568 | ambiguous | 0.306 | benign | -0.146 | Destabilizing | 0.971 | D | 0.638 | neutral | N | 0.456195405 | None | None | I |
| Y/T | 0.7673 | likely_pathogenic | 0.6347 | pathogenic | -0.089 | Destabilizing | 0.978 | D | 0.641 | neutral | None | None | None | None | I |
| Y/V | 0.7218 | likely_pathogenic | 0.5983 | pathogenic | -0.257 | Destabilizing | 0.754 | D | 0.576 | neutral | None | None | None | None | I |
| Y/W | 0.5139 | ambiguous | 0.4709 | ambiguous | -0.516 | Destabilizing | 0.998 | D | 0.536 | 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.