Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33282 | 100069;100070;100071 | chr2:178537363;178537362;178537361 | chr2:179402090;179402089;179402088 |
| N2AB | 31641 | 95146;95147;95148 | chr2:178537363;178537362;178537361 | chr2:179402090;179402089;179402088 |
| N2A | 30714 | 92365;92366;92367 | chr2:178537363;178537362;178537361 | chr2:179402090;179402089;179402088 |
| N2B | 24217 | 72874;72875;72876 | chr2:178537363;178537362;178537361 | chr2:179402090;179402089;179402088 |
| Novex-1 | 24342 | 73249;73250;73251 | chr2:178537363;178537362;178537361 | chr2:179402090;179402089;179402088 |
| Novex-2 | 24409 | 73450;73451;73452 | chr2:178537363;178537362;178537361 | chr2:179402090;179402089;179402088 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs747546215  |
-0.722 | None | N | 0.219 | 0.135 | None | gnomAD-2.1.1 | 4.6E-06 | None | None | None | None | N | None | 6.79E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs747546215 |
-0.722 | None | N | 0.219 | 0.135 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs747546215 |
-0.722 | None | N | 0.219 | 0.135 | None | gnomAD-4.0.0 | 5.44553E-06 | None | None | None | None | N | None | 7.0028E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.1636 | likely_benign | 0.1355 | benign | -1.029 | Destabilizing | 0.001 | N | 0.222 | neutral | None | None | None | None | N |
| I/C | 0.5204 | ambiguous | 0.4938 | ambiguous | -0.563 | Destabilizing | 0.599 | D | 0.499 | neutral | None | None | None | None | N |
| I/D | 0.3952 | ambiguous | 0.3296 | benign | -0.67 | Destabilizing | 0.174 | N | 0.579 | neutral | None | None | None | None | N |
| I/E | 0.3506 | ambiguous | 0.2832 | benign | -0.742 | Destabilizing | 0.134 | N | 0.503 | neutral | None | None | None | None | N |
| I/F | 0.127 | likely_benign | 0.1166 | benign | -0.881 | Destabilizing | 0.059 | N | 0.41 | neutral | N | 0.42302506 | None | None | N |
| I/G | 0.4748 | ambiguous | 0.4238 | ambiguous | -1.254 | Destabilizing | 0.08 | N | 0.505 | neutral | None | None | None | None | N |
| I/H | 0.3251 | likely_benign | 0.2715 | benign | -0.542 | Destabilizing | 0.654 | D | 0.551 | neutral | None | None | None | None | N |
| I/K | 0.2716 | likely_benign | 0.213 | benign | -0.697 | Destabilizing | 0.003 | N | 0.5 | neutral | None | None | None | None | N |
| I/L | 0.1007 | likely_benign | 0.0947 | benign | -0.531 | Destabilizing | None | N | 0.24 | neutral | N | 0.449075511 | None | None | N |
| I/M | 0.0899 | likely_benign | 0.0868 | benign | -0.403 | Destabilizing | None | N | 0.267 | neutral | N | 0.479051701 | None | None | N |
| I/N | 0.1332 | likely_benign | 0.1123 | benign | -0.381 | Destabilizing | 0.137 | N | 0.582 | neutral | N | 0.448382077 | None | None | N |
| I/P | 0.5661 | likely_pathogenic | 0.4995 | ambiguous | -0.664 | Destabilizing | 0.299 | N | 0.599 | neutral | None | None | None | None | N |
| I/Q | 0.2819 | likely_benign | 0.2261 | benign | -0.629 | Destabilizing | 0.08 | N | 0.617 | neutral | None | None | None | None | N |
| I/R | 0.2279 | likely_benign | 0.1801 | benign | -0.07 | Destabilizing | 0.077 | N | 0.627 | neutral | None | None | None | None | N |
| I/S | 0.138 | likely_benign | 0.1093 | benign | -0.841 | Destabilizing | 0.003 | N | 0.321 | neutral | N | 0.396913107 | None | None | N |
| I/T | 0.0895 | likely_benign | 0.0686 | benign | -0.807 | Destabilizing | None | N | 0.219 | neutral | N | 0.385677393 | None | None | N |
| I/V | 0.0642 | likely_benign | 0.0675 | benign | -0.664 | Destabilizing | None | N | 0.133 | neutral | N | 0.441360104 | None | None | N |
| I/W | 0.6951 | likely_pathogenic | 0.6132 | pathogenic | -0.913 | Destabilizing | 0.962 | D | 0.567 | neutral | None | None | None | None | N |
| I/Y | 0.3826 | ambiguous | 0.3225 | benign | -0.688 | Destabilizing | 0.065 | N | 0.552 | 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.