Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17877 | 53854;53855;53856 | chr2:178605666;178605665;178605664 | chr2:179470393;179470392;179470391 |
| N2AB | 16236 | 48931;48932;48933 | chr2:178605666;178605665;178605664 | chr2:179470393;179470392;179470391 |
| N2A | 15309 | 46150;46151;46152 | chr2:178605666;178605665;178605664 | chr2:179470393;179470392;179470391 |
| N2B | 8812 | 26659;26660;26661 | chr2:178605666;178605665;178605664 | chr2:179470393;179470392;179470391 |
| Novex-1 | 8937 | 27034;27035;27036 | chr2:178605666;178605665;178605664 | chr2:179470393;179470392;179470391 |
| Novex-2 | 9004 | 27235;27236;27237 | chr2:178605666;178605665;178605664 | chr2:179470393;179470392;179470391 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | rs776123623  |
-0.44 | 0.977 | N | 0.535 | 0.18 | 0.211220785272 | gnomAD-2.1.1 | 4.09E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.02E-06 | 0 |
| S/A | rs776123623 |
-0.44 | 0.977 | N | 0.535 | 0.18 | 0.211220785272 | gnomAD-4.0.0 | 1.3761E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.80748E-06 | 0 | 0 |
| S/P | rs776123623 |
-0.1 | 0.999 | N | 0.489 | 0.386 | 0.304435445954 | gnomAD-2.1.1 | 4.09E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.02E-06 | 0 |
| S/P | rs776123623 |
-0.1 | 0.999 | N | 0.489 | 0.386 | 0.304435445954 | gnomAD-4.0.0 | 6.88048E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.03741E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1583 | likely_benign | 0.148 | benign | -0.656 | Destabilizing | 0.977 | D | 0.535 | neutral | N | 0.474664148 | None | None | N |
| S/C | 0.2324 | likely_benign | 0.2265 | benign | -0.508 | Destabilizing | 1.0 | D | 0.523 | neutral | N | 0.489667758 | None | None | N |
| S/D | 0.4235 | ambiguous | 0.4329 | ambiguous | -0.513 | Destabilizing | 0.171 | N | 0.285 | neutral | None | None | None | None | N |
| S/E | 0.6412 | likely_pathogenic | 0.6344 | pathogenic | -0.538 | Destabilizing | 0.971 | D | 0.46 | neutral | None | None | None | None | N |
| S/F | 0.4761 | ambiguous | 0.4364 | ambiguous | -0.931 | Destabilizing | 0.999 | D | 0.583 | neutral | N | 0.484894818 | None | None | N |
| S/G | 0.1621 | likely_benign | 0.1498 | benign | -0.876 | Destabilizing | 0.964 | D | 0.505 | neutral | None | None | None | None | N |
| S/H | 0.3725 | ambiguous | 0.3459 | ambiguous | -1.405 | Destabilizing | 0.998 | D | 0.51 | neutral | None | None | None | None | N |
| S/I | 0.6563 | likely_pathogenic | 0.6346 | pathogenic | -0.183 | Destabilizing | 0.999 | D | 0.579 | neutral | None | None | None | None | N |
| S/K | 0.7367 | likely_pathogenic | 0.7183 | pathogenic | -0.761 | Destabilizing | 0.985 | D | 0.471 | neutral | None | None | None | None | N |
| S/L | 0.295 | likely_benign | 0.2736 | benign | -0.183 | Destabilizing | 0.998 | D | 0.509 | neutral | None | None | None | None | N |
| S/M | 0.338 | likely_benign | 0.314 | benign | 0.189 | Stabilizing | 1.0 | D | 0.507 | neutral | None | None | None | None | N |
| S/N | 0.1351 | likely_benign | 0.1375 | benign | -0.699 | Destabilizing | 0.271 | N | 0.142 | neutral | None | None | None | None | N |
| S/P | 0.981 | likely_pathogenic | 0.9727 | pathogenic | -0.308 | Destabilizing | 0.999 | D | 0.489 | neutral | N | 0.495997634 | None | None | N |
| S/Q | 0.5482 | ambiguous | 0.5327 | ambiguous | -0.937 | Destabilizing | 0.998 | D | 0.468 | neutral | None | None | None | None | N |
| S/R | 0.7283 | likely_pathogenic | 0.7105 | pathogenic | -0.578 | Destabilizing | 0.998 | D | 0.491 | neutral | None | None | None | None | N |
| S/T | 0.0902 | likely_benign | 0.0871 | benign | -0.71 | Destabilizing | 0.98 | D | 0.493 | neutral | N | 0.440265947 | None | None | N |
| S/V | 0.5739 | likely_pathogenic | 0.5349 | ambiguous | -0.308 | Destabilizing | 0.999 | D | 0.527 | neutral | None | None | None | None | N |
| S/W | 0.6341 | likely_pathogenic | 0.5922 | pathogenic | -0.9 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | N |
| S/Y | 0.3025 | likely_benign | 0.2868 | benign | -0.636 | Destabilizing | 0.999 | D | 0.579 | neutral | N | 0.48388086 | 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.