Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19290 | 58093;58094;58095 | chr2:178594626;178594625;178594624 | chr2:179459353;179459352;179459351 |
| N2AB | 17649 | 53170;53171;53172 | chr2:178594626;178594625;178594624 | chr2:179459353;179459352;179459351 |
| N2A | 16722 | 50389;50390;50391 | chr2:178594626;178594625;178594624 | chr2:179459353;179459352;179459351 |
| N2B | 10225 | 30898;30899;30900 | chr2:178594626;178594625;178594624 | chr2:179459353;179459352;179459351 |
| Novex-1 | 10350 | 31273;31274;31275 | chr2:178594626;178594625;178594624 | chr2:179459353;179459352;179459351 |
| Novex-2 | 10417 | 31474;31475;31476 | chr2:178594626;178594625;178594624 | chr2:179459353;179459352;179459351 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/G | rs749345178  |
-0.259 | 1.0 | N | 0.724 | 0.506 | None | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.98E-06 | 0 |
| D/G | rs749345178 |
-0.259 | 1.0 | N | 0.724 | 0.506 | None | gnomAD-4.0.0 | 1.60019E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.03933E-05 |
| D/H | rs770980138 |
0.092 | 1.0 | N | 0.643 | 0.431 | 0.32471235697 | gnomAD-2.1.1 | 8.14E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.8E-05 | 0 |
| D/H | rs770980138 |
0.092 | 1.0 | N | 0.643 | 0.431 | 0.32471235697 | gnomAD-4.0.0 | 4.80375E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.63006E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.2818 | likely_benign | 0.2775 | benign | -0.316 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | N | 0.492372423 | None | None | N |
| D/C | 0.7327 | likely_pathogenic | 0.7559 | pathogenic | 0.088 | Stabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | N |
| D/E | 0.2633 | likely_benign | 0.2364 | benign | -0.394 | Destabilizing | 1.0 | D | 0.424 | neutral | N | 0.46041472 | None | None | N |
| D/F | 0.5995 | likely_pathogenic | 0.5943 | pathogenic | -0.391 | Destabilizing | 1.0 | D | 0.702 | prob.neutral | None | None | None | None | N |
| D/G | 0.2897 | likely_benign | 0.2821 | benign | -0.516 | Destabilizing | 1.0 | D | 0.724 | prob.delet. | N | 0.48280879 | None | None | N |
| D/H | 0.4617 | ambiguous | 0.4683 | ambiguous | -0.39 | Destabilizing | 1.0 | D | 0.643 | neutral | N | 0.473890453 | None | None | N |
| D/I | 0.5548 | ambiguous | 0.5436 | ambiguous | 0.16 | Stabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | N |
| D/K | 0.6013 | likely_pathogenic | 0.5898 | pathogenic | 0.196 | Stabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | N |
| D/L | 0.5412 | ambiguous | 0.5302 | ambiguous | 0.16 | Stabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | None | N |
| D/M | 0.7176 | likely_pathogenic | 0.7061 | pathogenic | 0.402 | Stabilizing | 1.0 | D | 0.71 | prob.delet. | None | None | None | None | N |
| D/N | 0.1155 | likely_benign | 0.1251 | benign | 0.006 | Stabilizing | 1.0 | D | 0.612 | neutral | N | 0.474781166 | None | None | N |
| D/P | 0.9681 | likely_pathogenic | 0.9687 | pathogenic | 0.024 | Stabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | N |
| D/Q | 0.5378 | ambiguous | 0.5199 | ambiguous | 0.014 | Stabilizing | 1.0 | D | 0.636 | neutral | None | None | None | None | N |
| D/R | 0.6509 | likely_pathogenic | 0.6389 | pathogenic | 0.293 | Stabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | N |
| D/S | 0.2495 | likely_benign | 0.2538 | benign | -0.128 | Destabilizing | 1.0 | D | 0.663 | neutral | None | None | None | None | N |
| D/T | 0.4551 | ambiguous | 0.4527 | ambiguous | 0.018 | Stabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | N |
| D/V | 0.3623 | ambiguous | 0.3488 | ambiguous | 0.024 | Stabilizing | 1.0 | D | 0.719 | prob.delet. | N | 0.46805433 | None | None | N |
| D/W | 0.9221 | likely_pathogenic | 0.9173 | pathogenic | -0.302 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | N |
| D/Y | 0.2691 | likely_benign | 0.2614 | benign | -0.17 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | N | 0.510187869 | 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.