Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 13955 | 42088;42089;42090 | chr2:178635461;178635460;178635459 | chr2:179500188;179500187;179500186 |
| N2AB | 12314 | 37165;37166;37167 | chr2:178635461;178635460;178635459 | chr2:179500188;179500187;179500186 |
| N2A | 11387 | 34384;34385;34386 | chr2:178635461;178635460;178635459 | chr2:179500188;179500187;179500186 |
| N2B | 4890 | 14893;14894;14895 | chr2:178635461;178635460;178635459 | chr2:179500188;179500187;179500186 |
| Novex-1 | 5015 | 15268;15269;15270 | chr2:178635461;178635460;178635459 | chr2:179500188;179500187;179500186 |
| Novex-2 | 5082 | 15469;15470;15471 | chr2:178635461;178635460;178635459 | chr2:179500188;179500187;179500186 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/H | rs776863726  |
-0.72 | 0.621 | N | 0.512 | 0.258 | 0.443388199986 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| P/H | rs776863726 |
-0.72 | 0.621 | N | 0.512 | 0.258 | 0.443388199986 | gnomAD-4.0.0 | 2.0531E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.80424E-05 | 0 | 0 |
| P/L | rs776863726 |
None | 0.03 | N | 0.515 | 0.235 | 0.37479162749 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/L | rs776863726 |
None | 0.03 | N | 0.515 | 0.235 | 0.37479162749 | gnomAD-4.0.0 | 1.86646E-06 | None | None | None | None | N | None | 1.33743E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 8.49771E-07 | 0 | 1.60689E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.1889 | likely_benign | 0.101 | benign | -1.14 | Destabilizing | 0.012 | N | 0.431 | neutral | N | 0.477550138 | None | None | N |
| P/C | 0.8829 | likely_pathogenic | 0.6847 | pathogenic | -0.682 | Destabilizing | 0.685 | D | 0.553 | neutral | None | None | None | None | N |
| P/D | 0.8833 | likely_pathogenic | 0.7198 | pathogenic | -1.139 | Destabilizing | 0.039 | N | 0.436 | neutral | None | None | None | None | N |
| P/E | 0.7503 | likely_pathogenic | 0.5379 | ambiguous | -1.185 | Destabilizing | 0.039 | N | 0.435 | neutral | None | None | None | None | N |
| P/F | 0.8636 | likely_pathogenic | 0.7035 | pathogenic | -0.965 | Destabilizing | 0.366 | N | 0.569 | neutral | None | None | None | None | N |
| P/G | 0.6239 | likely_pathogenic | 0.4012 | ambiguous | -1.392 | Destabilizing | 0.039 | N | 0.511 | neutral | None | None | None | None | N |
| P/H | 0.6438 | likely_pathogenic | 0.416 | ambiguous | -0.958 | Destabilizing | 0.621 | D | 0.512 | neutral | N | 0.502319652 | None | None | N |
| P/I | 0.6453 | likely_pathogenic | 0.4227 | ambiguous | -0.573 | Destabilizing | 0.125 | N | 0.59 | neutral | None | None | None | None | N |
| P/K | 0.8116 | likely_pathogenic | 0.6124 | pathogenic | -1.093 | Destabilizing | 0.039 | N | 0.432 | neutral | None | None | None | None | N |
| P/L | 0.396 | ambiguous | 0.2205 | benign | -0.573 | Destabilizing | 0.03 | N | 0.515 | neutral | N | 0.500359001 | None | None | N |
| P/M | 0.6699 | likely_pathogenic | 0.41 | ambiguous | -0.433 | Destabilizing | 0.685 | D | 0.512 | neutral | None | None | None | None | N |
| P/N | 0.7411 | likely_pathogenic | 0.4642 | ambiguous | -0.786 | Destabilizing | 0.039 | N | 0.485 | neutral | None | None | None | None | N |
| P/Q | 0.5818 | likely_pathogenic | 0.3443 | ambiguous | -1.007 | Destabilizing | 0.221 | N | 0.5 | neutral | None | None | None | None | N |
| P/R | 0.6715 | likely_pathogenic | 0.476 | ambiguous | -0.503 | Destabilizing | 0.177 | N | 0.551 | neutral | N | 0.500555497 | None | None | N |
| P/S | 0.3659 | ambiguous | 0.17 | benign | -1.174 | Destabilizing | None | N | 0.282 | neutral | N | 0.467003709 | None | None | N |
| P/T | 0.245 | likely_benign | 0.1074 | benign | -1.125 | Destabilizing | None | N | 0.273 | neutral | N | 0.431966357 | None | None | N |
| P/V | 0.4848 | ambiguous | 0.2791 | benign | -0.727 | Destabilizing | 0.039 | N | 0.485 | neutral | None | None | None | None | N |
| P/W | 0.9513 | likely_pathogenic | 0.8893 | pathogenic | -1.127 | Destabilizing | 0.869 | D | 0.592 | neutral | None | None | None | None | N |
| P/Y | 0.8587 | likely_pathogenic | 0.6973 | pathogenic | -0.857 | Destabilizing | 0.366 | N | 0.56 | 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.