Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33048 | 99367;99368;99369 | chr2:178538687;178538686;178538685 | chr2:179403414;179403413;179403412 |
| N2AB | 31407 | 94444;94445;94446 | chr2:178538687;178538686;178538685 | chr2:179403414;179403413;179403412 |
| N2A | 30480 | 91663;91664;91665 | chr2:178538687;178538686;178538685 | chr2:179403414;179403413;179403412 |
| N2B | 23983 | 72172;72173;72174 | chr2:178538687;178538686;178538685 | chr2:179403414;179403413;179403412 |
| Novex-1 | 24108 | 72547;72548;72549 | chr2:178538687;178538686;178538685 | chr2:179403414;179403413;179403412 |
| Novex-2 | 24175 | 72748;72749;72750 | chr2:178538687;178538686;178538685 | chr2:179403414;179403413;179403412 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/G | rs1330792517  |
-0.839 | 0.183 | N | 0.413 | 0.137 | 0.190952846119 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/G | rs1330792517 |
-0.839 | 0.183 | N | 0.413 | 0.137 | 0.190952846119 | gnomAD-4.0.0 | 3.18265E-06 | None | None | None | None | N | None | 5.65675E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.02407E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0693 | likely_benign | 0.0637 | benign | -0.513 | Destabilizing | 0.061 | N | 0.343 | neutral | None | None | None | None | N |
| S/C | 0.0538 | likely_benign | 0.0437 | benign | -0.252 | Destabilizing | None | N | 0.305 | neutral | N | 0.333893418 | None | None | N |
| S/D | 0.7345 | likely_pathogenic | 0.7714 | pathogenic | 0.285 | Stabilizing | 0.816 | D | 0.447 | neutral | None | None | None | None | N |
| S/E | 0.8051 | likely_pathogenic | 0.819 | pathogenic | 0.365 | Stabilizing | 0.816 | D | 0.499 | neutral | None | None | None | None | N |
| S/F | 0.3159 | likely_benign | 0.3265 | benign | -0.67 | Destabilizing | 0.836 | D | 0.58 | neutral | None | None | None | None | N |
| S/G | 0.0844 | likely_benign | 0.0791 | benign | -0.808 | Destabilizing | 0.183 | N | 0.413 | neutral | N | 0.436807142 | None | None | N |
| S/H | 0.5334 | ambiguous | 0.5209 | ambiguous | -1.049 | Destabilizing | 0.94 | D | 0.557 | neutral | None | None | None | None | N |
| S/I | 0.1415 | likely_benign | 0.1453 | benign | 0.182 | Stabilizing | 0.351 | N | 0.511 | neutral | N | 0.360807873 | None | None | N |
| S/K | 0.8901 | likely_pathogenic | 0.9012 | pathogenic | -0.017 | Destabilizing | 0.593 | D | 0.443 | neutral | None | None | None | None | N |
| S/L | 0.1402 | likely_benign | 0.1652 | benign | 0.182 | Stabilizing | 0.129 | N | 0.433 | neutral | None | None | None | None | N |
| S/M | 0.2257 | likely_benign | 0.2479 | benign | 0.049 | Stabilizing | 0.94 | D | 0.558 | neutral | None | None | None | None | N |
| S/N | 0.1982 | likely_benign | 0.2203 | benign | -0.265 | Destabilizing | 0.77 | D | 0.505 | neutral | N | 0.458625209 | None | None | N |
| S/P | 0.5336 | ambiguous | 0.6217 | pathogenic | -0.015 | Destabilizing | 0.94 | D | 0.571 | neutral | None | None | None | None | N |
| S/Q | 0.681 | likely_pathogenic | 0.6875 | pathogenic | -0.181 | Destabilizing | 0.94 | D | 0.561 | neutral | None | None | None | None | N |
| S/R | 0.8308 | likely_pathogenic | 0.8434 | pathogenic | -0.154 | Destabilizing | 0.921 | D | 0.573 | neutral | N | 0.475997461 | None | None | N |
| S/T | 0.0887 | likely_benign | 0.0969 | benign | -0.233 | Destabilizing | 0.183 | N | 0.443 | neutral | N | 0.424165918 | None | None | N |
| S/V | 0.1434 | likely_benign | 0.1451 | benign | -0.015 | Destabilizing | 0.264 | N | 0.467 | neutral | None | None | None | None | N |
| S/W | 0.4772 | ambiguous | 0.4938 | ambiguous | -0.764 | Destabilizing | 0.983 | D | 0.624 | neutral | None | None | None | None | N |
| S/Y | 0.2513 | likely_benign | 0.2422 | benign | -0.369 | Destabilizing | 0.94 | D | 0.583 | 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.