Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28740 | 86443;86444;86445 | chr2:178559914;178559913;178559912 | chr2:179424641;179424640;179424639 |
| N2AB | 27099 | 81520;81521;81522 | chr2:178559914;178559913;178559912 | chr2:179424641;179424640;179424639 |
| N2A | 26172 | 78739;78740;78741 | chr2:178559914;178559913;178559912 | chr2:179424641;179424640;179424639 |
| N2B | 19675 | 59248;59249;59250 | chr2:178559914;178559913;178559912 | chr2:179424641;179424640;179424639 |
| Novex-1 | 19800 | 59623;59624;59625 | chr2:178559914;178559913;178559912 | chr2:179424641;179424640;179424639 |
| Novex-2 | 19867 | 59824;59825;59826 | chr2:178559914;178559913;178559912 | chr2:179424641;179424640;179424639 |
| 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/C | rs1348508376  |
-0.017 | 0.778 | N | 0.546 | 0.391 | 0.405422107966 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| S/C | rs1348508376 |
-0.017 | 0.778 | N | 0.546 | 0.391 | 0.405422107966 | gnomAD-4.0.0 | 6.84277E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99484E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1089 | likely_benign | 0.116 | benign | -0.802 | Destabilizing | 0.026 | N | 0.434 | neutral | N | 0.47955463 | None | None | N |
| S/C | 0.1226 | likely_benign | 0.1237 | benign | -0.517 | Destabilizing | 0.778 | D | 0.546 | neutral | N | 0.496065951 | None | None | N |
| S/D | 0.7418 | likely_pathogenic | 0.7405 | pathogenic | -0.999 | Destabilizing | 0.147 | N | 0.388 | neutral | None | None | None | None | N |
| S/E | 0.8327 | likely_pathogenic | 0.8293 | pathogenic | -0.849 | Destabilizing | 0.147 | N | 0.357 | neutral | None | None | None | None | N |
| S/F | 0.4441 | ambiguous | 0.4804 | ambiguous | -0.59 | Destabilizing | 0.481 | N | 0.719 | prob.delet. | N | 0.510029149 | None | None | N |
| S/G | 0.1321 | likely_benign | 0.1389 | benign | -1.186 | Destabilizing | 0.147 | N | 0.392 | neutral | None | None | None | None | N |
| S/H | 0.7061 | likely_pathogenic | 0.7165 | pathogenic | -1.511 | Destabilizing | 0.934 | D | 0.551 | neutral | None | None | None | None | N |
| S/I | 0.3135 | likely_benign | 0.3212 | benign | 0.16 | Stabilizing | 0.233 | N | 0.534 | neutral | None | None | None | None | N |
| S/K | 0.9277 | likely_pathogenic | 0.9284 | pathogenic | -0.423 | Destabilizing | 0.147 | N | 0.379 | neutral | None | None | None | None | N |
| S/L | 0.1664 | likely_benign | 0.175 | benign | 0.16 | Stabilizing | 0.08 | N | 0.541 | neutral | None | None | None | None | N |
| S/M | 0.2999 | likely_benign | 0.3204 | benign | 0.174 | Stabilizing | 0.823 | D | 0.555 | neutral | None | None | None | None | N |
| S/N | 0.3772 | ambiguous | 0.3919 | ambiguous | -0.91 | Destabilizing | 0.147 | N | 0.439 | neutral | None | None | None | None | N |
| S/P | 0.3421 | ambiguous | 0.3572 | ambiguous | -0.125 | Destabilizing | 0.481 | N | 0.506 | neutral | N | 0.472935266 | None | None | N |
| S/Q | 0.8023 | likely_pathogenic | 0.8124 | pathogenic | -0.758 | Destabilizing | 0.552 | D | 0.501 | neutral | None | None | None | None | N |
| S/R | 0.8976 | likely_pathogenic | 0.9044 | pathogenic | -0.673 | Destabilizing | 0.378 | N | 0.517 | neutral | None | None | None | None | N |
| S/T | 0.0723 | likely_benign | 0.0749 | benign | -0.684 | Destabilizing | None | N | 0.133 | neutral | N | 0.485422234 | None | None | N |
| S/V | 0.2589 | likely_benign | 0.262 | benign | -0.125 | Destabilizing | 0.08 | N | 0.529 | neutral | None | None | None | None | N |
| S/W | 0.6365 | likely_pathogenic | 0.6816 | pathogenic | -0.756 | Destabilizing | 0.934 | D | 0.798 | deleterious | None | None | None | None | N |
| S/Y | 0.5091 | ambiguous | 0.5304 | ambiguous | -0.363 | Destabilizing | 0.481 | N | 0.739 | deleterious | N | 0.521550038 | 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.