Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1522 | 4789;4790;4791 | chr2:178777501;178777500;178777499 | chr2:179642228;179642227;179642226 |
| N2AB | 1522 | 4789;4790;4791 | chr2:178777501;178777500;178777499 | chr2:179642228;179642227;179642226 |
| N2A | 1522 | 4789;4790;4791 | chr2:178777501;178777500;178777499 | chr2:179642228;179642227;179642226 |
| N2B | 1476 | 4651;4652;4653 | chr2:178777501;178777500;178777499 | chr2:179642228;179642227;179642226 |
| Novex-1 | 1476 | 4651;4652;4653 | chr2:178777501;178777500;178777499 | chr2:179642228;179642227;179642226 |
| Novex-2 | 1476 | 4651;4652;4653 | chr2:178777501;178777500;178777499 | chr2:179642228;179642227;179642226 |
| Novex-3 | 1522 | 4789;4790;4791 | chr2:178777501;178777500;178777499 | chr2:179642228;179642227;179642226 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | None | None | 1.0 | D | 0.789 | 0.486 | 0.749107425127 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.66327E-05 |
| P/S | rs1261123391  |
-0.023 | 1.0 | D | 0.749 | 0.522 | 0.496364318313 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| P/S | rs1261123391 |
-0.023 | 1.0 | D | 0.749 | 0.522 | 0.496364318313 | gnomAD-4.0.0 | 1.59127E-06 | None | None | None | None | N | None | 0 | 2.28739E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0614 | likely_benign | 0.0626 | benign | -0.615 | Destabilizing | 1.0 | D | 0.668 | neutral | D | 0.528234898 | None | None | N |
| P/C | 0.5402 | ambiguous | 0.5516 | ambiguous | -0.646 | Destabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | N |
| P/D | 0.4653 | ambiguous | 0.4764 | ambiguous | -0.399 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | N |
| P/E | 0.2458 | likely_benign | 0.2595 | benign | -0.526 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | N |
| P/F | 0.4372 | ambiguous | 0.4397 | ambiguous | -0.955 | Destabilizing | 1.0 | D | 0.75 | deleterious | None | None | None | None | N |
| P/G | 0.3227 | likely_benign | 0.3345 | benign | -0.732 | Destabilizing | 1.0 | D | 0.776 | deleterious | None | None | None | None | N |
| P/H | 0.1906 | likely_benign | 0.1896 | benign | -0.328 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | D | 0.670763268 | None | None | N |
| P/I | 0.2069 | likely_benign | 0.2141 | benign | -0.458 | Destabilizing | 1.0 | D | 0.783 | deleterious | None | None | None | None | N |
| P/K | 0.2316 | likely_benign | 0.2301 | benign | -0.389 | Destabilizing | 1.0 | D | 0.736 | prob.delet. | None | None | None | None | N |
| P/L | 0.0882 | likely_benign | 0.0891 | benign | -0.458 | Destabilizing | 1.0 | D | 0.789 | deleterious | D | 0.529653955 | None | None | N |
| P/M | 0.2663 | likely_benign | 0.2737 | benign | -0.311 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | N |
| P/N | 0.3385 | likely_benign | 0.3505 | ambiguous | -0.145 | Destabilizing | 1.0 | D | 0.785 | deleterious | None | None | None | None | N |
| P/Q | 0.1387 | likely_benign | 0.1417 | benign | -0.452 | Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | N |
| P/R | 0.1482 | likely_benign | 0.1428 | benign | 0.157 | Stabilizing | 1.0 | D | 0.775 | deleterious | D | 0.530756702 | None | None | N |
| P/S | 0.1121 | likely_benign | 0.1148 | benign | -0.511 | Destabilizing | 1.0 | D | 0.749 | deleterious | D | 0.531717396 | None | None | N |
| P/T | 0.0954 | likely_benign | 0.0993 | benign | -0.542 | Destabilizing | 1.0 | D | 0.746 | deleterious | D | 0.575509291 | None | None | N |
| P/V | 0.1448 | likely_benign | 0.1534 | benign | -0.476 | Destabilizing | 1.0 | D | 0.77 | deleterious | None | None | None | None | N |
| P/W | 0.6834 | likely_pathogenic | 0.6799 | pathogenic | -0.995 | Destabilizing | 1.0 | D | 0.744 | deleterious | None | None | None | None | N |
| P/Y | 0.4234 | ambiguous | 0.4343 | ambiguous | -0.68 | Destabilizing | 1.0 | D | 0.763 | deleterious | 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.