Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17147 | 51664;51665;51666 | chr2:178609984;178609983;178609982 | chr2:179474711;179474710;179474709 |
| N2AB | 15506 | 46741;46742;46743 | chr2:178609984;178609983;178609982 | chr2:179474711;179474710;179474709 |
| N2A | 14579 | 43960;43961;43962 | chr2:178609984;178609983;178609982 | chr2:179474711;179474710;179474709 |
| N2B | 8082 | 24469;24470;24471 | chr2:178609984;178609983;178609982 | chr2:179474711;179474710;179474709 |
| Novex-1 | 8207 | 24844;24845;24846 | chr2:178609984;178609983;178609982 | chr2:179474711;179474710;179474709 |
| Novex-2 | 8274 | 25045;25046;25047 | chr2:178609984;178609983;178609982 | chr2:179474711;179474710;179474709 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/H | rs1193239944  |
-0.431 | 0.98 | N | 0.351 | 0.193 | 0.361558571881 | gnomAD-2.1.1 | 3.2E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.51E-05 | 0 |
| P/H | rs1193239944 |
-0.431 | 0.98 | N | 0.351 | 0.193 | 0.361558571881 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| P/H | rs1193239944 |
-0.431 | 0.98 | N | 0.351 | 0.193 | 0.361558571881 | gnomAD-4.0.0 | 5.58967E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.6365E-06 | 0 | 0 |
| P/T | rs876658065 |
None | 0.651 | N | 0.38 | 0.241 | 0.324436698001 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| P/T | rs876658065 |
None | 0.651 | N | 0.38 | 0.241 | 0.324436698001 | gnomAD-4.0.0 | 2.57391E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.80001E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0838 | likely_benign | 0.0814 | benign | -0.424 | Destabilizing | 0.01 | N | 0.14 | neutral | N | 0.470548782 | None | None | I |
| P/C | 0.4683 | ambiguous | 0.4051 | ambiguous | -0.556 | Destabilizing | 0.995 | D | 0.425 | neutral | None | None | None | None | I |
| P/D | 0.8124 | likely_pathogenic | 0.7594 | pathogenic | -0.068 | Destabilizing | 0.946 | D | 0.445 | neutral | None | None | None | None | I |
| P/E | 0.4572 | ambiguous | 0.4049 | ambiguous | -0.19 | Destabilizing | 0.712 | D | 0.382 | neutral | None | None | None | None | I |
| P/F | 0.6009 | likely_pathogenic | 0.524 | ambiguous | -0.8 | Destabilizing | 0.982 | D | 0.447 | neutral | None | None | None | None | I |
| P/G | 0.5252 | ambiguous | 0.4707 | ambiguous | -0.531 | Destabilizing | 0.712 | D | 0.393 | neutral | None | None | None | None | I |
| P/H | 0.2702 | likely_benign | 0.2218 | benign | -0.159 | Destabilizing | 0.98 | D | 0.351 | neutral | N | 0.473580376 | None | None | I |
| P/I | 0.235 | likely_benign | 0.2155 | benign | -0.297 | Destabilizing | 0.946 | D | 0.487 | neutral | None | None | None | None | I |
| P/K | 0.2607 | likely_benign | 0.2358 | benign | -0.122 | Destabilizing | 0.553 | D | 0.406 | neutral | None | None | None | None | I |
| P/L | 0.1396 | likely_benign | 0.1167 | benign | -0.297 | Destabilizing | 0.651 | D | 0.381 | neutral | N | 0.482312881 | None | None | I |
| P/M | 0.3176 | likely_benign | 0.285 | benign | -0.186 | Destabilizing | 0.995 | D | 0.352 | neutral | None | None | None | None | I |
| P/N | 0.5686 | likely_pathogenic | 0.511 | ambiguous | 0.108 | Stabilizing | 0.897 | D | 0.415 | neutral | None | None | None | None | I |
| P/Q | 0.1727 | likely_benign | 0.1504 | benign | -0.182 | Destabilizing | 0.897 | D | 0.443 | neutral | None | None | None | None | I |
| P/R | 0.1603 | likely_benign | 0.1379 | benign | 0.34 | Stabilizing | 0.006 | N | 0.287 | neutral | N | 0.471935649 | None | None | I |
| P/S | 0.2342 | likely_benign | 0.2105 | benign | -0.293 | Destabilizing | 0.483 | N | 0.425 | neutral | N | 0.516187858 | None | None | I |
| P/T | 0.1674 | likely_benign | 0.1479 | benign | -0.318 | Destabilizing | 0.651 | D | 0.38 | neutral | N | 0.464083722 | None | None | I |
| P/V | 0.1619 | likely_benign | 0.1506 | benign | -0.305 | Destabilizing | 0.712 | D | 0.416 | neutral | None | None | None | None | I |
| P/W | 0.8108 | likely_pathogenic | 0.7285 | pathogenic | -0.843 | Destabilizing | 0.995 | D | 0.583 | neutral | None | None | None | None | I |
| P/Y | 0.5753 | likely_pathogenic | 0.5037 | ambiguous | -0.497 | Destabilizing | 0.982 | D | 0.444 | neutral | None | None | None | None | I |
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.