Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22754 | 68485;68486;68487 | chr2:178578680;178578679;178578678 | chr2:179443407;179443406;179443405 |
| N2AB | 21113 | 63562;63563;63564 | chr2:178578680;178578679;178578678 | chr2:179443407;179443406;179443405 |
| N2A | 20186 | 60781;60782;60783 | chr2:178578680;178578679;178578678 | chr2:179443407;179443406;179443405 |
| N2B | 13689 | 41290;41291;41292 | chr2:178578680;178578679;178578678 | chr2:179443407;179443406;179443405 |
| Novex-1 | 13814 | 41665;41666;41667 | chr2:178578680;178578679;178578678 | chr2:179443407;179443406;179443405 |
| Novex-2 | 13881 | 41866;41867;41868 | chr2:178578680;178578679;178578678 | chr2:179443407;179443406;179443405 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/H | None | None | 0.295 | N | 0.394 | 0.215 | 0.245101548738 | gnomAD-4.0.0 | 6.85119E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.16673E-05 | 0 |
| D/N | rs755823330  |
0.079 | 0.024 | N | 0.215 | 0.175 | 0.167679373172 | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.95E-06 | 0 |
| D/N | rs755823330 |
0.079 | 0.024 | N | 0.215 | 0.175 | 0.167679373172 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| D/N | rs755823330 |
0.079 | 0.024 | N | 0.215 | 0.175 | 0.167679373172 | gnomAD-4.0.0 | 1.36515E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.86599E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1293 | likely_benign | 0.1188 | benign | -0.486 | Destabilizing | None | N | 0.112 | neutral | N | 0.415989152 | None | None | N |
| D/C | 0.4975 | ambiguous | 0.4666 | ambiguous | -0.164 | Destabilizing | 0.356 | N | 0.422 | neutral | None | None | None | None | N |
| D/E | 0.1253 | likely_benign | 0.0945 | benign | -0.415 | Destabilizing | None | N | 0.067 | neutral | N | 0.411177978 | None | None | N |
| D/F | 0.4591 | ambiguous | 0.425 | ambiguous | -0.188 | Destabilizing | 0.356 | N | 0.481 | neutral | None | None | None | None | N |
| D/G | 0.1885 | likely_benign | 0.1719 | benign | -0.746 | Destabilizing | None | N | 0.089 | neutral | N | 0.50018383 | None | None | N |
| D/H | 0.2322 | likely_benign | 0.2287 | benign | -0.202 | Destabilizing | 0.295 | N | 0.394 | neutral | N | 0.472210581 | None | None | N |
| D/I | 0.3387 | likely_benign | 0.2901 | benign | 0.172 | Stabilizing | 0.072 | N | 0.473 | neutral | None | None | None | None | N |
| D/K | 0.3797 | ambiguous | 0.3497 | ambiguous | 0.063 | Stabilizing | 0.016 | N | 0.329 | neutral | None | None | None | None | N |
| D/L | 0.3178 | likely_benign | 0.2845 | benign | 0.172 | Stabilizing | 0.016 | N | 0.39 | neutral | None | None | None | None | N |
| D/M | 0.4653 | ambiguous | 0.3949 | ambiguous | 0.371 | Stabilizing | 0.628 | D | 0.439 | neutral | None | None | None | None | N |
| D/N | 0.1137 | likely_benign | 0.1019 | benign | -0.397 | Destabilizing | 0.024 | N | 0.215 | neutral | N | 0.428032943 | None | None | N |
| D/P | 0.8799 | likely_pathogenic | 0.85 | pathogenic | -0.024 | Destabilizing | 0.136 | N | 0.378 | neutral | None | None | None | None | N |
| D/Q | 0.2867 | likely_benign | 0.2495 | benign | -0.319 | Destabilizing | 0.038 | N | 0.219 | neutral | None | None | None | None | N |
| D/R | 0.3752 | ambiguous | 0.369 | ambiguous | 0.256 | Stabilizing | 0.038 | N | 0.426 | neutral | None | None | None | None | N |
| D/S | 0.1061 | likely_benign | 0.0993 | benign | -0.522 | Destabilizing | 0.001 | N | 0.076 | neutral | None | None | None | None | N |
| D/T | 0.1944 | likely_benign | 0.1664 | benign | -0.311 | Destabilizing | None | N | 0.104 | neutral | None | None | None | None | N |
| D/V | 0.2058 | likely_benign | 0.1809 | benign | -0.024 | Destabilizing | 0.012 | N | 0.376 | neutral | N | 0.493700574 | None | None | N |
| D/W | 0.7856 | likely_pathogenic | 0.7724 | pathogenic | 0.023 | Stabilizing | 0.864 | D | 0.423 | neutral | None | None | None | None | N |
| D/Y | 0.2022 | likely_benign | 0.1972 | benign | 0.059 | Stabilizing | 0.56 | D | 0.465 | neutral | N | 0.520156457 | 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.