Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3259 | 10000;10001;10002 | chr2:178764740;178764739;178764738 | chr2:179629467;179629466;179629465 |
| N2AB | 3259 | 10000;10001;10002 | chr2:178764740;178764739;178764738 | chr2:179629467;179629466;179629465 |
| N2A | 3259 | 10000;10001;10002 | chr2:178764740;178764739;178764738 | chr2:179629467;179629466;179629465 |
| N2B | 3213 | 9862;9863;9864 | chr2:178764740;178764739;178764738 | chr2:179629467;179629466;179629465 |
| Novex-1 | 3213 | 9862;9863;9864 | chr2:178764740;178764739;178764738 | chr2:179629467;179629466;179629465 |
| Novex-2 | 3213 | 9862;9863;9864 | chr2:178764740;178764739;178764738 | chr2:179629467;179629466;179629465 |
| Novex-3 | 3259 | 10000;10001;10002 | chr2:178764740;178764739;178764738 | chr2:179629467;179629466;179629465 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/R | None | None | 0.002 | N | 0.46 | 0.388 | 0.627088449377 | gnomAD-4.0.0 | 1.59077E-06 | None | None | disulfide | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85667E-06 | 0 | 0 |
| C/S | rs1258913609  |
None | 0.003 | N | 0.309 | 0.213 | 0.486282253068 | gnomAD-3.1.2 | 1.31E-05 | None | None | disulfide | None | N | None | 0 | 1.3089E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| C/S | rs1258913609 |
None | 0.003 | N | 0.309 | 0.213 | 0.486282253068 | gnomAD-4.0.0 | 1.31409E-05 | None | None | disulfide | None | N | None | 0 | 1.3089E-04 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| C/Y | rs794729585 |
None | 0.921 | N | 0.523 | 0.338 | 0.658862992856 | gnomAD-3.1.2 | 6.57E-06 | None | None | disulfide | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| C/Y | rs794729585 |
None | 0.921 | N | 0.523 | 0.338 | 0.658862992856 | gnomAD-4.0.0 | 6.08966E-06 | None | None | disulfide | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.22944E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/A | 0.3232 | likely_benign | 0.5007 | ambiguous | -1.889 | Destabilizing | 0.061 | N | 0.335 | neutral | None | None | disulfide | None | N |
| C/D | 0.6133 | likely_pathogenic | 0.8676 | pathogenic | -0.922 | Destabilizing | 0.418 | N | 0.486 | neutral | None | None | disulfide | None | N |
| C/E | 0.6582 | likely_pathogenic | 0.8691 | pathogenic | -0.785 | Destabilizing | 0.418 | N | 0.461 | neutral | None | None | disulfide | None | N |
| C/F | 0.2057 | likely_benign | 0.3765 | ambiguous | -1.18 | Destabilizing | 0.794 | D | 0.531 | neutral | N | 0.477549911 | disulfide | None | N |
| C/G | 0.1711 | likely_benign | 0.3203 | benign | -2.221 | Highly Destabilizing | 0.101 | N | 0.44 | neutral | N | 0.489183726 | disulfide | None | N |
| C/H | 0.272 | likely_benign | 0.5227 | ambiguous | -2.284 | Highly Destabilizing | 0.836 | D | 0.533 | neutral | None | None | disulfide | None | N |
| C/I | 0.4828 | ambiguous | 0.6702 | pathogenic | -1.015 | Destabilizing | 0.418 | N | 0.483 | neutral | None | None | disulfide | None | N |
| C/K | 0.5934 | likely_pathogenic | 0.8276 | pathogenic | -1.287 | Destabilizing | 0.129 | N | 0.447 | neutral | None | None | disulfide | None | N |
| C/L | 0.4537 | ambiguous | 0.6413 | pathogenic | -1.015 | Destabilizing | 0.129 | N | 0.422 | neutral | None | None | disulfide | None | N |
| C/M | 0.6331 | likely_pathogenic | 0.7647 | pathogenic | 0.026 | Stabilizing | 0.94 | D | 0.484 | neutral | None | None | disulfide | None | N |
| C/N | 0.4131 | ambiguous | 0.6616 | pathogenic | -1.381 | Destabilizing | 0.264 | N | 0.487 | neutral | None | None | disulfide | None | N |
| C/P | 0.9344 | likely_pathogenic | 0.9882 | pathogenic | -1.282 | Destabilizing | 0.593 | D | 0.569 | neutral | None | None | disulfide | None | N |
| C/Q | 0.3738 | ambiguous | 0.6279 | pathogenic | -1.222 | Destabilizing | 0.716 | D | 0.568 | neutral | None | None | disulfide | None | N |
| C/R | 0.2092 | likely_benign | 0.4425 | ambiguous | -1.231 | Destabilizing | 0.002 | N | 0.46 | neutral | N | 0.415444036 | disulfide | None | N |
| C/S | 0.1605 | likely_benign | 0.2815 | benign | -1.881 | Destabilizing | 0.003 | N | 0.309 | neutral | N | 0.366398701 | disulfide | None | N |
| C/T | 0.2842 | likely_benign | 0.43 | ambiguous | -1.563 | Destabilizing | 0.004 | N | 0.292 | neutral | None | None | disulfide | None | N |
| C/V | 0.4008 | ambiguous | 0.5431 | ambiguous | -1.282 | Destabilizing | 0.129 | N | 0.432 | neutral | None | None | disulfide | None | N |
| C/W | 0.4503 | ambiguous | 0.7192 | pathogenic | -1.266 | Destabilizing | 0.978 | D | 0.54 | neutral | N | 0.493779559 | disulfide | None | N |
| C/Y | 0.2611 | likely_benign | 0.5068 | ambiguous | -1.23 | Destabilizing | 0.921 | D | 0.523 | neutral | N | 0.477434028 | disulfide | 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.