Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 13914 | 41965;41966;41967 | chr2:178635584;178635583;178635582 | chr2:179500311;179500310;179500309 |
| N2AB | 12273 | 37042;37043;37044 | chr2:178635584;178635583;178635582 | chr2:179500311;179500310;179500309 |
| N2A | 11346 | 34261;34262;34263 | chr2:178635584;178635583;178635582 | chr2:179500311;179500310;179500309 |
| N2B | 4849 | 14770;14771;14772 | chr2:178635584;178635583;178635582 | chr2:179500311;179500310;179500309 |
| Novex-1 | 4974 | 15145;15146;15147 | chr2:178635584;178635583;178635582 | chr2:179500311;179500310;179500309 |
| Novex-2 | 5041 | 15346;15347;15348 | chr2:178635584;178635583;178635582 | chr2:179500311;179500310;179500309 |
| 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/S | rs755785975  |
-0.184 | 0.92 | N | 0.371 | 0.218 | 0.167679373172 | gnomAD-2.1.1 | 1.2E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.79E-05 | None | 0 | None | 0 | 1.8E-05 | 0 |
| P/S | rs755785975 |
-0.184 | 0.92 | N | 0.371 | 0.218 | 0.167679373172 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| P/S | rs755785975 |
-0.184 | 0.92 | N | 0.371 | 0.218 | 0.167679373172 | gnomAD-4.0.0 | 1.25469E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.71072E-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 | 0.122 | likely_benign | 0.1282 | benign | -0.641 | Destabilizing | 0.236 | N | 0.375 | neutral | N | 0.472382699 | None | None | N |
| P/C | 0.7973 | likely_pathogenic | 0.7926 | pathogenic | -0.541 | Destabilizing | 1.0 | D | 0.693 | prob.delet. | None | None | None | None | N |
| P/D | 0.6783 | likely_pathogenic | 0.6916 | pathogenic | -0.597 | Destabilizing | 0.984 | D | 0.419 | neutral | None | None | None | None | N |
| P/E | 0.5107 | ambiguous | 0.5247 | ambiguous | -0.705 | Destabilizing | 0.984 | D | 0.435 | neutral | None | None | None | None | N |
| P/F | 0.7465 | likely_pathogenic | 0.7488 | pathogenic | -0.823 | Destabilizing | 0.998 | D | 0.71 | prob.delet. | None | None | None | None | N |
| P/G | 0.5294 | ambiguous | 0.5284 | ambiguous | -0.803 | Destabilizing | 0.968 | D | 0.487 | neutral | None | None | None | None | N |
| P/H | 0.4701 | ambiguous | 0.4453 | ambiguous | -0.454 | Destabilizing | 0.999 | D | 0.611 | neutral | N | 0.476356359 | None | None | N |
| P/I | 0.5193 | ambiguous | 0.5419 | ambiguous | -0.354 | Destabilizing | 0.991 | D | 0.67 | prob.neutral | None | None | None | None | N |
| P/K | 0.5771 | likely_pathogenic | 0.5651 | pathogenic | -0.634 | Destabilizing | 0.984 | D | 0.428 | neutral | None | None | None | None | N |
| P/L | 0.1977 | likely_benign | 0.1972 | benign | -0.354 | Destabilizing | 0.958 | D | 0.545 | neutral | N | 0.470557234 | None | None | N |
| P/M | 0.5291 | ambiguous | 0.5446 | ambiguous | -0.315 | Destabilizing | 1.0 | D | 0.61 | neutral | None | None | None | None | N |
| P/N | 0.6379 | likely_pathogenic | 0.6414 | pathogenic | -0.284 | Destabilizing | 0.995 | D | 0.557 | neutral | None | None | None | None | N |
| P/Q | 0.3551 | ambiguous | 0.3585 | ambiguous | -0.545 | Destabilizing | 0.998 | D | 0.463 | neutral | None | None | None | None | N |
| P/R | 0.4665 | ambiguous | 0.4506 | ambiguous | -0.089 | Destabilizing | 0.994 | D | 0.625 | neutral | N | 0.473744532 | None | None | N |
| P/S | 0.2331 | likely_benign | 0.2171 | benign | -0.616 | Destabilizing | 0.92 | D | 0.371 | neutral | N | 0.470791602 | None | None | N |
| P/T | 0.1956 | likely_benign | 0.1802 | benign | -0.627 | Destabilizing | 0.115 | N | 0.313 | neutral | N | 0.441157988 | None | None | N |
| P/V | 0.3656 | ambiguous | 0.3867 | ambiguous | -0.414 | Destabilizing | 0.968 | D | 0.477 | neutral | None | None | None | None | N |
| P/W | 0.905 | likely_pathogenic | 0.9003 | pathogenic | -0.925 | Destabilizing | 1.0 | D | 0.705 | prob.delet. | None | None | None | None | N |
| P/Y | 0.7664 | likely_pathogenic | 0.7609 | pathogenic | -0.632 | Destabilizing | 0.998 | D | 0.698 | prob.delet. | 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.