Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17462 | 52609;52610;52611 | chr2:178608627;178608626;178608625 | chr2:179473354;179473353;179473352 |
| N2AB | 15821 | 47686;47687;47688 | chr2:178608627;178608626;178608625 | chr2:179473354;179473353;179473352 |
| N2A | 14894 | 44905;44906;44907 | chr2:178608627;178608626;178608625 | chr2:179473354;179473353;179473352 |
| N2B | 8397 | 25414;25415;25416 | chr2:178608627;178608626;178608625 | chr2:179473354;179473353;179473352 |
| Novex-1 | 8522 | 25789;25790;25791 | chr2:178608627;178608626;178608625 | chr2:179473354;179473353;179473352 |
| Novex-2 | 8589 | 25990;25991;25992 | chr2:178608627;178608626;178608625 | chr2:179473354;179473353;179473352 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/F | None | None | None | N | 0.303 | 0.064 | 0.0806252709748 | gnomAD-4.0.0 | 3.19535E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.73247E-06 | 0 | 0 |
| L/P | rs1216814159  |
-1.168 | 0.303 | N | 0.729 | 0.307 | 0.627711000292 | gnomAD-2.1.1 | 4.09E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.05E-06 | 0 |
| L/P | rs1216814159 |
-1.168 | 0.303 | N | 0.729 | 0.307 | 0.627711000292 | 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 |
| L/P | rs1216814159 |
-1.168 | 0.303 | N | 0.729 | 0.307 | 0.627711000292 | gnomAD-4.0.0 | 8.06969E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.24689E-05 | None | 0 | 0 | 1.01807E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.3975 | ambiguous | 0.3711 | ambiguous | -2.171 | Highly Destabilizing | 0.001 | N | 0.311 | neutral | None | None | None | None | N |
| L/C | 0.4235 | ambiguous | 0.4275 | ambiguous | -1.412 | Destabilizing | 0.869 | D | 0.567 | neutral | None | None | None | None | N |
| L/D | 0.9539 | likely_pathogenic | 0.9464 | pathogenic | -2.416 | Highly Destabilizing | 0.366 | N | 0.721 | deleterious | None | None | None | None | N |
| L/E | 0.7106 | likely_pathogenic | 0.7005 | pathogenic | -2.154 | Highly Destabilizing | 0.366 | N | 0.71 | prob.delet. | None | None | None | None | N |
| L/F | 0.1417 | likely_benign | 0.1384 | benign | -1.327 | Destabilizing | None | N | 0.303 | neutral | N | 0.466223185 | None | None | N |
| L/G | 0.8539 | likely_pathogenic | 0.8272 | pathogenic | -2.698 | Highly Destabilizing | 0.075 | N | 0.669 | prob.neutral | None | None | None | None | N |
| L/H | 0.5199 | ambiguous | 0.4928 | ambiguous | -2.09 | Highly Destabilizing | 0.447 | N | 0.693 | prob.delet. | N | 0.50418414 | None | None | N |
| L/I | 0.0845 | likely_benign | 0.0866 | benign | -0.631 | Destabilizing | 0.012 | N | 0.505 | neutral | N | 0.407942885 | None | None | N |
| L/K | 0.6736 | likely_pathogenic | 0.6356 | pathogenic | -1.604 | Destabilizing | 0.221 | N | 0.591 | neutral | None | None | None | None | N |
| L/M | 0.1096 | likely_benign | 0.1051 | benign | -0.634 | Destabilizing | 0.007 | N | 0.367 | neutral | None | None | None | None | N |
| L/N | 0.8287 | likely_pathogenic | 0.8059 | pathogenic | -2.101 | Highly Destabilizing | 0.366 | N | 0.73 | deleterious | None | None | None | None | N |
| L/P | 0.9517 | likely_pathogenic | 0.9331 | pathogenic | -1.129 | Destabilizing | 0.303 | N | 0.729 | deleterious | N | 0.485598379 | None | None | N |
| L/Q | 0.4569 | ambiguous | 0.4299 | ambiguous | -1.865 | Destabilizing | 0.366 | N | 0.625 | neutral | None | None | None | None | N |
| L/R | 0.5684 | likely_pathogenic | 0.5259 | ambiguous | -1.56 | Destabilizing | 0.303 | N | 0.601 | neutral | N | 0.504010782 | None | None | N |
| L/S | 0.6729 | likely_pathogenic | 0.6353 | pathogenic | -2.75 | Highly Destabilizing | 0.039 | N | 0.589 | neutral | None | None | None | None | N |
| L/T | 0.3358 | likely_benign | 0.3213 | benign | -2.326 | Highly Destabilizing | 0.075 | N | 0.565 | neutral | None | None | None | None | N |
| L/V | 0.0773 | likely_benign | 0.0778 | benign | -1.129 | Destabilizing | None | N | 0.199 | neutral | N | 0.339581665 | None | None | N |
| L/W | 0.5062 | ambiguous | 0.4672 | ambiguous | -1.615 | Destabilizing | 0.685 | D | 0.594 | neutral | None | None | None | None | N |
| L/Y | 0.4649 | ambiguous | 0.4452 | ambiguous | -1.302 | Destabilizing | 0.001 | N | 0.302 | 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.