Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16910 | 50953;50954;50955 | chr2:178611501;178611500;178611499 | chr2:179476228;179476227;179476226 |
| N2AB | 15269 | 46030;46031;46032 | chr2:178611501;178611500;178611499 | chr2:179476228;179476227;179476226 |
| N2A | 14342 | 43249;43250;43251 | chr2:178611501;178611500;178611499 | chr2:179476228;179476227;179476226 |
| N2B | 7845 | 23758;23759;23760 | chr2:178611501;178611500;178611499 | chr2:179476228;179476227;179476226 |
| Novex-1 | 7970 | 24133;24134;24135 | chr2:178611501;178611500;178611499 | chr2:179476228;179476227;179476226 |
| Novex-2 | 8037 | 24334;24335;24336 | chr2:178611501;178611500;178611499 | chr2:179476228;179476227;179476226 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/S | rs1161195119  |
-2.683 | 0.998 | N | 0.712 | 0.429 | 0.72290962679 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.98E-06 | 0 |
| L/S | rs1161195119 |
-2.683 | 0.998 | N | 0.712 | 0.429 | 0.72290962679 | gnomAD-4.0.0 | 1.59288E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86146E-06 | 0 | 0 |
| L/V | rs1559779803 |
None | 0.996 | N | 0.581 | 0.167 | 0.405150804464 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 3.16456E-03 | 0 | 0 | 0 |
| L/V | rs1559779803 |
None | 0.996 | N | 0.581 | 0.167 | 0.405150804464 | gnomAD-4.0.0 | 6.57505E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 3.40136E-03 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.4455 | ambiguous | 0.5499 | ambiguous | -1.955 | Destabilizing | 0.997 | D | 0.579 | neutral | None | None | None | None | N |
| L/C | 0.486 | ambiguous | 0.6834 | pathogenic | -1.08 | Destabilizing | 1.0 | D | 0.778 | deleterious | None | None | None | None | N |
| L/D | 0.9024 | likely_pathogenic | 0.9392 | pathogenic | -1.926 | Destabilizing | 1.0 | D | 0.81 | deleterious | None | None | None | None | N |
| L/E | 0.6 | likely_pathogenic | 0.701 | pathogenic | -1.76 | Destabilizing | 1.0 | D | 0.798 | deleterious | None | None | None | None | N |
| L/F | 0.3877 | ambiguous | 0.4402 | ambiguous | -1.19 | Destabilizing | 1.0 | D | 0.76 | deleterious | D | 0.522397058 | None | None | N |
| L/G | 0.6813 | likely_pathogenic | 0.8172 | pathogenic | -2.404 | Highly Destabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | N |
| L/H | 0.495 | ambiguous | 0.5991 | pathogenic | -1.587 | Destabilizing | 1.0 | D | 0.836 | deleterious | None | None | None | None | N |
| L/I | 0.1915 | likely_benign | 0.2126 | benign | -0.702 | Destabilizing | 0.997 | D | 0.519 | neutral | None | None | None | None | N |
| L/K | 0.4307 | ambiguous | 0.5 | ambiguous | -1.372 | Destabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | N |
| L/M | 0.1393 | likely_benign | 0.1655 | benign | -0.562 | Destabilizing | 1.0 | D | 0.745 | deleterious | N | 0.506326738 | None | None | N |
| L/N | 0.5035 | ambiguous | 0.6807 | pathogenic | -1.596 | Destabilizing | 1.0 | D | 0.806 | deleterious | None | None | None | None | N |
| L/P | 0.5112 | ambiguous | 0.6494 | pathogenic | -1.097 | Destabilizing | 1.0 | D | 0.819 | deleterious | None | None | None | None | N |
| L/Q | 0.2465 | likely_benign | 0.343 | ambiguous | -1.559 | Destabilizing | 1.0 | D | 0.818 | deleterious | None | None | None | None | N |
| L/R | 0.3189 | likely_benign | 0.4006 | ambiguous | -1.002 | Destabilizing | 1.0 | D | 0.777 | deleterious | None | None | None | None | N |
| L/S | 0.5107 | ambiguous | 0.6195 | pathogenic | -2.233 | Highly Destabilizing | 0.998 | D | 0.712 | prob.delet. | N | 0.467607002 | None | None | N |
| L/T | 0.2138 | likely_benign | 0.2808 | benign | -1.929 | Destabilizing | 0.91 | D | 0.354 | neutral | None | None | None | None | N |
| L/V | 0.1526 | likely_benign | 0.1851 | benign | -1.097 | Destabilizing | 0.996 | D | 0.581 | neutral | N | 0.511000379 | None | None | N |
| L/W | 0.624 | likely_pathogenic | 0.6989 | pathogenic | -1.452 | Destabilizing | 1.0 | D | 0.818 | deleterious | D | 0.589976999 | None | None | N |
| L/Y | 0.6791 | likely_pathogenic | 0.7711 | pathogenic | -1.125 | Destabilizing | 1.0 | D | 0.798 | 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.