Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19264 | 58015;58016;58017 | chr2:178595564;178595563;178595562 | chr2:179460291;179460290;179460289 |
| N2AB | 17623 | 53092;53093;53094 | chr2:178595564;178595563;178595562 | chr2:179460291;179460290;179460289 |
| N2A | 16696 | 50311;50312;50313 | chr2:178595564;178595563;178595562 | chr2:179460291;179460290;179460289 |
| N2B | 10199 | 30820;30821;30822 | chr2:178595564;178595563;178595562 | chr2:179460291;179460290;179460289 |
| Novex-1 | 10324 | 31195;31196;31197 | chr2:178595564;178595563;178595562 | chr2:179460291;179460290;179460289 |
| Novex-2 | 10391 | 31396;31397;31398 | chr2:178595564;178595563;178595562 | chr2:179460291;179460290;179460289 |
| 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/M | rs2154188219  |
None | 0.638 | N | 0.616 | 0.231 | 0.15556083564 | gnomAD-4.0.0 | 3.3963E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.83601E-05 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs1242461429 |
-0.315 | 0.201 | N | 0.631 | 0.326 | None | gnomAD-2.1.1 | 5.21E-06 | None | None | None | None | I | None | 0 | 3.55E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs1242461429 |
-0.315 | 0.201 | N | 0.631 | 0.326 | None | gnomAD-4.0.0 | 3.51511E-06 | None | None | None | None | I | None | 0 | 2.56502E-05 | None | 0 | 0 | None | 0 | 0 | 3.66864E-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 | 0.3634 | ambiguous | 0.4451 | ambiguous | -0.458 | Destabilizing | 0.25 | N | 0.579 | neutral | None | None | None | None | I |
| I/C | 0.6897 | likely_pathogenic | 0.738 | pathogenic | -0.757 | Destabilizing | 0.947 | D | 0.638 | neutral | None | None | None | None | I |
| I/D | 0.9441 | likely_pathogenic | 0.9613 | pathogenic | 0.055 | Stabilizing | 0.826 | D | 0.729 | prob.delet. | None | None | None | None | I |
| I/E | 0.8571 | likely_pathogenic | 0.8983 | pathogenic | -0.04 | Destabilizing | 0.826 | D | 0.731 | prob.delet. | None | None | None | None | I |
| I/F | 0.216 | likely_benign | 0.2695 | benign | -0.538 | Destabilizing | 0.638 | D | 0.613 | neutral | N | 0.482944863 | None | None | I |
| I/G | 0.8663 | likely_pathogenic | 0.9021 | pathogenic | -0.579 | Destabilizing | 0.826 | D | 0.729 | prob.delet. | None | None | None | None | I |
| I/H | 0.7385 | likely_pathogenic | 0.7892 | pathogenic | 0.098 | Stabilizing | 0.982 | D | 0.757 | deleterious | None | None | None | None | I |
| I/K | 0.736 | likely_pathogenic | 0.8006 | pathogenic | -0.2 | Destabilizing | 0.826 | D | 0.731 | prob.delet. | None | None | None | None | I |
| I/L | 0.1773 | likely_benign | 0.2068 | benign | -0.271 | Destabilizing | 0.043 | N | 0.399 | neutral | N | 0.46787941 | None | None | I |
| I/M | 0.1504 | likely_benign | 0.1756 | benign | -0.415 | Destabilizing | 0.638 | D | 0.616 | neutral | N | 0.494353935 | None | None | I |
| I/N | 0.6405 | likely_pathogenic | 0.7041 | pathogenic | -0.104 | Destabilizing | 0.916 | D | 0.739 | prob.delet. | N | 0.492062992 | None | None | I |
| I/P | 0.9501 | likely_pathogenic | 0.9636 | pathogenic | -0.302 | Destabilizing | 0.826 | D | 0.743 | deleterious | None | None | None | None | I |
| I/Q | 0.7392 | likely_pathogenic | 0.7864 | pathogenic | -0.297 | Destabilizing | 0.935 | D | 0.74 | deleterious | None | None | None | None | I |
| I/R | 0.5776 | likely_pathogenic | 0.6706 | pathogenic | 0.286 | Stabilizing | 0.826 | D | 0.741 | deleterious | None | None | None | None | I |
| I/S | 0.5032 | ambiguous | 0.5904 | pathogenic | -0.555 | Destabilizing | 0.638 | D | 0.673 | neutral | N | 0.506051009 | None | None | I |
| I/T | 0.2475 | likely_benign | 0.3177 | benign | -0.542 | Destabilizing | 0.201 | N | 0.631 | neutral | N | 0.46517704 | None | None | I |
| I/V | 0.0711 | likely_benign | 0.0772 | benign | -0.302 | Destabilizing | 0.001 | N | 0.267 | neutral | N | 0.456083549 | None | None | I |
| I/W | 0.839 | likely_pathogenic | 0.8757 | pathogenic | -0.543 | Destabilizing | 0.982 | D | 0.789 | deleterious | None | None | None | None | I |
| I/Y | 0.6429 | likely_pathogenic | 0.7237 | pathogenic | -0.291 | Destabilizing | 0.826 | D | 0.635 | 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.