Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29419 | 88480;88481;88482 | chr2:178556899;178556898;178556897 | chr2:179421626;179421625;179421624 |
| N2AB | 27778 | 83557;83558;83559 | chr2:178556899;178556898;178556897 | chr2:179421626;179421625;179421624 |
| N2A | 26851 | 80776;80777;80778 | chr2:178556899;178556898;178556897 | chr2:179421626;179421625;179421624 |
| N2B | 20354 | 61285;61286;61287 | chr2:178556899;178556898;178556897 | chr2:179421626;179421625;179421624 |
| Novex-1 | 20479 | 61660;61661;61662 | chr2:178556899;178556898;178556897 | chr2:179421626;179421625;179421624 |
| Novex-2 | 20546 | 61861;61862;61863 | chr2:178556899;178556898;178556897 | chr2:179421626;179421625;179421624 |
| 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/S | rs1406975324  |
-1.135 | 0.029 | N | 0.617 | 0.21 | 0.630346058385 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| I/S | rs1406975324 |
-1.135 | 0.029 | N | 0.617 | 0.21 | 0.630346058385 | gnomAD-4.0.0 | 1.59131E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43275E-05 | 0 |
| I/V | rs1273849394 |
None | None | N | 0.231 | 0.066 | 0.262662153117 | gnomAD-4.0.0 | 1.59131E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85796E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.308 | likely_benign | 0.2316 | benign | -1.344 | Destabilizing | 0.016 | N | 0.515 | neutral | None | None | None | None | I |
| I/C | 0.5704 | likely_pathogenic | 0.4794 | ambiguous | -0.992 | Destabilizing | 0.676 | D | 0.627 | neutral | None | None | None | None | I |
| I/D | 0.7161 | likely_pathogenic | 0.5984 | pathogenic | -0.24 | Destabilizing | 0.214 | N | 0.674 | neutral | None | None | None | None | I |
| I/E | 0.6204 | likely_pathogenic | 0.5093 | ambiguous | -0.279 | Destabilizing | 0.214 | N | 0.666 | neutral | None | None | None | None | I |
| I/F | 0.158 | likely_benign | 0.1185 | benign | -1.13 | Destabilizing | None | N | 0.319 | neutral | N | 0.385282243 | None | None | I |
| I/G | 0.6049 | likely_pathogenic | 0.4704 | ambiguous | -1.599 | Destabilizing | 0.072 | N | 0.667 | neutral | None | None | None | None | I |
| I/H | 0.4907 | ambiguous | 0.3932 | ambiguous | -0.758 | Destabilizing | 0.864 | D | 0.658 | neutral | None | None | None | None | I |
| I/K | 0.4622 | ambiguous | 0.3805 | ambiguous | -0.645 | Destabilizing | 0.214 | N | 0.667 | neutral | None | None | None | None | I |
| I/L | 0.1058 | likely_benign | 0.0927 | benign | -0.753 | Destabilizing | None | N | 0.235 | neutral | N | 0.380913786 | None | None | I |
| I/M | 0.1154 | likely_benign | 0.0972 | benign | -0.608 | Destabilizing | 0.171 | N | 0.652 | neutral | N | 0.468130126 | None | None | I |
| I/N | 0.2685 | likely_benign | 0.2197 | benign | -0.406 | Destabilizing | 0.171 | N | 0.677 | prob.neutral | N | 0.503837423 | None | None | I |
| I/P | 0.7395 | likely_pathogenic | 0.6341 | pathogenic | -0.917 | Destabilizing | 0.356 | N | 0.678 | prob.neutral | None | None | None | None | I |
| I/Q | 0.4454 | ambiguous | 0.3636 | ambiguous | -0.62 | Destabilizing | 0.356 | N | 0.656 | neutral | None | None | None | None | I |
| I/R | 0.3814 | ambiguous | 0.304 | benign | -0.087 | Destabilizing | 0.214 | N | 0.673 | neutral | None | None | None | None | I |
| I/S | 0.2513 | likely_benign | 0.2111 | benign | -1.094 | Destabilizing | 0.029 | N | 0.617 | neutral | N | 0.428128943 | None | None | I |
| I/T | 0.1755 | likely_benign | 0.1562 | benign | -1.009 | Destabilizing | None | N | 0.372 | neutral | N | 0.460990723 | None | None | I |
| I/V | 0.0635 | likely_benign | 0.0572 | benign | -0.917 | Destabilizing | None | N | 0.231 | neutral | N | 0.378836273 | None | None | I |
| I/W | 0.7744 | likely_pathogenic | 0.6772 | pathogenic | -1.076 | Destabilizing | 0.864 | D | 0.659 | neutral | None | None | None | None | I |
| I/Y | 0.4537 | ambiguous | 0.3694 | ambiguous | -0.848 | Destabilizing | 0.12 | N | 0.644 | 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.