Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 7597 | 23014;23015;23016 | chr2:178721874;178721873;178721872 | chr2:179586601;179586600;179586599 |
| N2AB | 7280 | 22063;22064;22065 | chr2:178721874;178721873;178721872 | chr2:179586601;179586600;179586599 |
| N2A | 6353 | 19282;19283;19284 | chr2:178721874;178721873;178721872 | chr2:179586601;179586600;179586599 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/K | rs1265324107  |
0.563 | 0.028 | N | 0.255 | 0.226 | 0.530705155676 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.56E-05 | None | 0 | None | 0 | 0 | 0 |
| M/K | rs1265324107 |
0.563 | 0.028 | N | 0.255 | 0.226 | 0.530705155676 | gnomAD-4.0.0 | 1.36975E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.03931E-05 | None | 0 | 0 | 0 | 0 | 0 |
| M/L | None | None | 0.012 | N | 0.203 | 0.171 | 0.592685350901 | gnomAD-4.0.0 | 1.20033E-06 | None | None | None | None | N | None | 6.33473E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| M/T | None | None | 0.028 | N | 0.242 | 0.179 | 0.607789150232 | gnomAD-4.0.0 | 2.7395E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.60038E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.1269 | likely_benign | 0.1304 | benign | -1.383 | Destabilizing | 0.016 | N | 0.251 | neutral | None | None | None | None | N |
| M/C | 0.4935 | ambiguous | 0.5318 | ambiguous | -0.873 | Destabilizing | 0.901 | D | 0.395 | neutral | None | None | None | None | N |
| M/D | 0.4555 | ambiguous | 0.4634 | ambiguous | -0.216 | Destabilizing | None | N | 0.317 | neutral | None | None | None | None | N |
| M/E | 0.2331 | likely_benign | 0.2267 | benign | -0.22 | Destabilizing | 0.016 | N | 0.296 | neutral | None | None | None | None | N |
| M/F | 0.1667 | likely_benign | 0.1726 | benign | -0.588 | Destabilizing | 0.001 | N | 0.079 | neutral | None | None | None | None | N |
| M/G | 0.2732 | likely_benign | 0.2921 | benign | -1.651 | Destabilizing | 0.036 | N | 0.298 | neutral | None | None | None | None | N |
| M/H | 0.2043 | likely_benign | 0.2144 | benign | -0.681 | Destabilizing | 0.001 | N | 0.257 | neutral | None | None | None | None | N |
| M/I | 0.1445 | likely_benign | 0.1472 | benign | -0.722 | Destabilizing | 0.061 | N | 0.308 | neutral | N | 0.397993329 | None | None | N |
| M/K | 0.1109 | likely_benign | 0.107 | benign | -0.238 | Destabilizing | 0.028 | N | 0.255 | neutral | N | 0.410554408 | None | None | N |
| M/L | 0.1107 | likely_benign | 0.112 | benign | -0.722 | Destabilizing | 0.012 | N | 0.203 | neutral | N | 0.394953024 | None | None | N |
| M/N | 0.1817 | likely_benign | 0.2009 | benign | -0.057 | Destabilizing | 0.036 | N | 0.291 | neutral | None | None | None | None | N |
| M/P | 0.8911 | likely_pathogenic | 0.8982 | pathogenic | -0.915 | Destabilizing | 0.26 | N | 0.397 | neutral | None | None | None | None | N |
| M/Q | 0.1277 | likely_benign | 0.1272 | benign | -0.186 | Destabilizing | 0.007 | N | 0.079 | neutral | None | None | None | None | N |
| M/R | 0.1079 | likely_benign | 0.1064 | benign | 0.292 | Stabilizing | 0.116 | N | 0.34 | neutral | N | 0.391104642 | None | None | N |
| M/S | 0.1026 | likely_benign | 0.1152 | benign | -0.625 | Destabilizing | 0.001 | N | 0.144 | neutral | None | None | None | None | N |
| M/T | 0.0577 | likely_benign | 0.0585 | benign | -0.52 | Destabilizing | 0.028 | N | 0.242 | neutral | N | 0.325954299 | None | None | N |
| M/V | 0.063 | likely_benign | 0.0629 | benign | -0.915 | Destabilizing | 0.054 | N | 0.227 | neutral | N | 0.382831876 | None | None | N |
| M/W | 0.3599 | ambiguous | 0.3887 | ambiguous | -0.497 | Destabilizing | 0.901 | D | 0.399 | neutral | None | None | None | None | N |
| M/Y | 0.3104 | likely_benign | 0.3333 | benign | -0.489 | Destabilizing | 0.08 | N | 0.362 | 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.