Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2261 | 7006;7007;7008 | chr2:178774930;178774929;178774928 | chr2:179639657;179639656;179639655 |
| N2AB | 2261 | 7006;7007;7008 | chr2:178774930;178774929;178774928 | chr2:179639657;179639656;179639655 |
| N2A | 2261 | 7006;7007;7008 | chr2:178774930;178774929;178774928 | chr2:179639657;179639656;179639655 |
| N2B | 2215 | 6868;6869;6870 | chr2:178774930;178774929;178774928 | chr2:179639657;179639656;179639655 |
| Novex-1 | 2215 | 6868;6869;6870 | chr2:178774930;178774929;178774928 | chr2:179639657;179639656;179639655 |
| Novex-2 | 2215 | 6868;6869;6870 | chr2:178774930;178774929;178774928 | chr2:179639657;179639656;179639655 |
| Novex-3 | 2261 | 7006;7007;7008 | chr2:178774930;178774929;178774928 | chr2:179639657;179639656;179639655 |
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/L | rs755035176  |
-0.299 | None | N | 0.092 | 0.076 | 0.465806656444 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| I/L | rs755035176 |
-0.299 | None | N | 0.092 | 0.076 | 0.465806656444 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/L | rs755035176 |
-0.299 | None | N | 0.092 | 0.076 | 0.465806656444 | gnomAD-4.0.0 | 1.23939E-06 | None | None | None | None | N | None | 1.33284E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.09803E-05 | 0 |
| I/T | rs751757338 |
-0.902 | 0.001 | N | 0.225 | 0.232 | 0.526842377483 | gnomAD-2.1.1 | 7.1E-06 | None | None | None | None | N | None | 4.01E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 7.78E-06 | 0 |
| I/T | rs751757338 |
-0.902 | 0.001 | N | 0.225 | 0.232 | 0.526842377483 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs751757338 |
-0.902 | 0.001 | N | 0.225 | 0.232 | 0.526842377483 | gnomAD-4.0.0 | 3.7184E-06 | None | None | None | None | N | None | 2.66973E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.54266E-06 | 0 | 1.60077E-05 |
| I/V | None | None | 0.019 | N | 0.25 | 0.059 | 0.572690963233 | gnomAD-4.0.0 | 6.84276E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99426E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.1939 | likely_benign | 0.2026 | benign | -1.506 | Destabilizing | 0.055 | N | 0.424 | neutral | None | None | None | None | N |
| I/C | 0.6067 | likely_pathogenic | 0.6143 | pathogenic | -0.882 | Destabilizing | 0.958 | D | 0.392 | neutral | None | None | None | None | N |
| I/D | 0.4721 | ambiguous | 0.4906 | ambiguous | -0.963 | Destabilizing | 0.22 | N | 0.473 | neutral | None | None | None | None | N |
| I/E | 0.3188 | likely_benign | 0.3238 | benign | -0.981 | Destabilizing | 0.22 | N | 0.488 | neutral | None | None | None | None | N |
| I/F | 0.1206 | likely_benign | 0.1244 | benign | -1.046 | Destabilizing | 0.096 | N | 0.255 | neutral | N | 0.509392031 | None | None | N |
| I/G | 0.5602 | ambiguous | 0.5718 | pathogenic | -1.8 | Destabilizing | 0.22 | N | 0.472 | neutral | None | None | None | None | N |
| I/H | 0.1954 | likely_benign | 0.2103 | benign | -0.977 | Destabilizing | 0.002 | N | 0.402 | neutral | None | None | None | None | N |
| I/K | 0.1634 | likely_benign | 0.1708 | benign | -1.116 | Destabilizing | 0.22 | N | 0.498 | neutral | None | None | None | None | N |
| I/L | 0.0984 | likely_benign | 0.0993 | benign | -0.784 | Destabilizing | None | N | 0.092 | neutral | N | 0.502104086 | None | None | N |
| I/M | 0.0884 | likely_benign | 0.0893 | benign | -0.602 | Destabilizing | 0.427 | N | 0.394 | neutral | N | 0.512155107 | None | None | N |
| I/N | 0.1252 | likely_benign | 0.1371 | benign | -0.901 | Destabilizing | 0.175 | N | 0.477 | neutral | N | 0.497575752 | None | None | N |
| I/P | 0.9297 | likely_pathogenic | 0.9244 | pathogenic | -0.992 | Destabilizing | 0.667 | D | 0.459 | neutral | None | None | None | None | N |
| I/Q | 0.2101 | likely_benign | 0.2201 | benign | -1.097 | Destabilizing | 0.667 | D | 0.453 | neutral | None | None | None | None | N |
| I/R | 0.1186 | likely_benign | 0.1218 | benign | -0.473 | Destabilizing | 0.497 | N | 0.471 | neutral | None | None | None | None | N |
| I/S | 0.1548 | likely_benign | 0.1624 | benign | -1.464 | Destabilizing | 0.096 | N | 0.435 | neutral | N | 0.482417704 | None | None | N |
| I/T | 0.0885 | likely_benign | 0.0885 | benign | -1.373 | Destabilizing | 0.001 | N | 0.225 | neutral | N | 0.403970716 | None | None | N |
| I/V | 0.0806 | likely_benign | 0.0827 | benign | -0.992 | Destabilizing | 0.019 | N | 0.25 | neutral | N | 0.481305799 | None | None | N |
| I/W | 0.6148 | likely_pathogenic | 0.6323 | pathogenic | -1.1 | Destabilizing | 0.883 | D | 0.412 | neutral | None | None | None | None | N |
| I/Y | 0.3236 | likely_benign | 0.345 | ambiguous | -0.898 | Destabilizing | 0.004 | N | 0.273 | 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.