Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 4760 | 14503;14504;14505 | chr2:178738175;178738174;178738173 | chr2:179602902;179602901;179602900 |
| N2AB | 4443 | 13552;13553;13554 | chr2:178738175;178738174;178738173 | chr2:179602902;179602901;179602900 |
| N2A | 3516 | 10771;10772;10773 | chr2:178738175;178738174;178738173 | chr2:179602902;179602901;179602900 |
| N2B | 4397 | 13414;13415;13416 | chr2:178738175;178738174;178738173 | chr2:179602902;179602901;179602900 |
| Novex-1 | 4522 | 13789;13790;13791 | chr2:178738175;178738174;178738173 | chr2:179602902;179602901;179602900 |
| Novex-2 | 4589 | 13990;13991;13992 | chr2:178738175;178738174;178738173 | chr2:179602902;179602901;179602900 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/R | rs2081864609  |
None | 0.81 | N | 0.49 | 0.295 | 0.782511395319 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| L/R | rs2081864609 |
None | 0.81 | N | 0.49 | 0.295 | 0.782511395319 | gnomAD-4.0.0 | 6.57151E-06 | None | None | None | None | N | None | 2.41173E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| L/V | rs2081864970 |
None | 0.007 | N | 0.059 | 0.073 | 0.425615883737 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| L/V | rs2081864970 |
None | 0.007 | N | 0.059 | 0.073 | 0.425615883737 | gnomAD-4.0.0 | 6.57341E-06 | None | None | None | None | N | None | 2.41418E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.5362 | ambiguous | 0.4955 | ambiguous | -1.202 | Destabilizing | 0.4 | N | 0.312 | neutral | None | None | None | None | N |
| L/C | 0.8011 | likely_pathogenic | 0.7736 | pathogenic | -0.75 | Destabilizing | 0.992 | D | 0.38 | neutral | None | None | None | None | N |
| L/D | 0.9269 | likely_pathogenic | 0.901 | pathogenic | -0.348 | Destabilizing | 0.92 | D | 0.501 | neutral | None | None | None | None | N |
| L/E | 0.6751 | likely_pathogenic | 0.6126 | pathogenic | -0.387 | Destabilizing | 0.85 | D | 0.479 | neutral | None | None | None | None | N |
| L/F | 0.2438 | likely_benign | 0.219 | benign | -0.853 | Destabilizing | 0.005 | N | 0.106 | neutral | None | None | None | None | N |
| L/G | 0.7826 | likely_pathogenic | 0.7411 | pathogenic | -1.471 | Destabilizing | 0.617 | D | 0.479 | neutral | None | None | None | None | N |
| L/H | 0.4472 | ambiguous | 0.3751 | ambiguous | -0.631 | Destabilizing | 0.992 | D | 0.467 | neutral | None | None | None | None | N |
| L/I | 0.21 | likely_benign | 0.1899 | benign | -0.57 | Destabilizing | 0.25 | N | 0.309 | neutral | None | None | None | None | N |
| L/K | 0.5 | ambiguous | 0.433 | ambiguous | -0.665 | Destabilizing | 0.85 | D | 0.451 | neutral | None | None | None | None | N |
| L/M | 0.2297 | likely_benign | 0.2066 | benign | -0.448 | Destabilizing | 0.099 | N | 0.217 | neutral | N | 0.49177538 | None | None | N |
| L/N | 0.6795 | likely_pathogenic | 0.6182 | pathogenic | -0.405 | Destabilizing | 0.92 | D | 0.51 | neutral | None | None | None | None | N |
| L/P | 0.5026 | ambiguous | 0.4887 | ambiguous | -0.747 | Destabilizing | 0.009 | N | 0.352 | neutral | N | 0.490848369 | None | None | N |
| L/Q | 0.2905 | likely_benign | 0.2413 | benign | -0.617 | Destabilizing | 0.896 | D | 0.484 | neutral | N | 0.486991097 | None | None | N |
| L/R | 0.3455 | ambiguous | 0.3053 | benign | -0.085 | Destabilizing | 0.81 | D | 0.49 | neutral | N | 0.488877833 | None | None | N |
| L/S | 0.5507 | ambiguous | 0.4851 | ambiguous | -1.034 | Destabilizing | 0.617 | D | 0.435 | neutral | None | None | None | None | N |
| L/T | 0.4956 | ambiguous | 0.4387 | ambiguous | -0.957 | Destabilizing | 0.617 | D | 0.317 | neutral | None | None | None | None | N |
| L/V | 0.2211 | likely_benign | 0.2134 | benign | -0.747 | Destabilizing | 0.007 | N | 0.059 | neutral | N | 0.491258547 | None | None | N |
| L/W | 0.452 | ambiguous | 0.3982 | ambiguous | -0.849 | Destabilizing | 0.992 | D | 0.45 | neutral | None | None | None | None | N |
| L/Y | 0.5761 | likely_pathogenic | 0.5494 | ambiguous | -0.631 | Destabilizing | 0.739 | D | 0.397 | neutral | None | None | 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.