Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1016 | 3271;3272;3273 | chr2:178782860;178782859;178782858 | chr2:179647587;179647586;179647585 |
| N2AB | 1016 | 3271;3272;3273 | chr2:178782860;178782859;178782858 | chr2:179647587;179647586;179647585 |
| N2A | 1016 | 3271;3272;3273 | chr2:178782860;178782859;178782858 | chr2:179647587;179647586;179647585 |
| N2B | 970 | 3133;3134;3135 | chr2:178782860;178782859;178782858 | chr2:179647587;179647586;179647585 |
| Novex-1 | 970 | 3133;3134;3135 | chr2:178782860;178782859;178782858 | chr2:179647587;179647586;179647585 |
| Novex-2 | 970 | 3133;3134;3135 | chr2:178782860;178782859;178782858 | chr2:179647587;179647586;179647585 |
| Novex-3 | 1016 | 3271;3272;3273 | chr2:178782860;178782859;178782858 | chr2:179647587;179647586;179647585 |
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/G | rs756789081  |
-1.227 | 0.052 | D | 0.524 | 0.264 | 0.21279746466 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.83E-06 | 0 |
| S/G | rs756789081 |
-1.227 | 0.052 | D | 0.524 | 0.264 | 0.21279746466 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| S/G | rs756789081 |
-1.227 | 0.052 | D | 0.524 | 0.264 | 0.21279746466 | gnomAD-4.0.0 | 2.5616E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.78416E-06 | 0 | 0 |
| S/R | None | None | 0.117 | N | 0.619 | 0.271 | 0.180583059064 | gnomAD-4.0.0 | 1.59105E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85714E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1126 | likely_benign | 0.126 | benign | -0.809 | Destabilizing | 0.016 | N | 0.319 | neutral | None | None | None | None | N |
| S/C | 0.1813 | likely_benign | 0.2307 | benign | -0.635 | Destabilizing | 0.484 | N | 0.605 | neutral | D | 0.557317305 | None | None | N |
| S/D | 0.7156 | likely_pathogenic | 0.7855 | pathogenic | -0.939 | Destabilizing | 0.149 | N | 0.547 | neutral | None | None | None | None | N |
| S/E | 0.6814 | likely_pathogenic | 0.7468 | pathogenic | -0.851 | Destabilizing | 0.149 | N | 0.541 | neutral | None | None | None | None | N |
| S/F | 0.3233 | likely_benign | 0.3972 | ambiguous | -0.818 | Destabilizing | 0.555 | D | 0.688 | prob.neutral | None | None | None | None | N |
| S/G | 0.2363 | likely_benign | 0.2889 | benign | -1.127 | Destabilizing | 0.052 | N | 0.524 | neutral | D | 0.597637375 | None | None | N |
| S/H | 0.4159 | ambiguous | 0.4665 | ambiguous | -1.574 | Destabilizing | 0.791 | D | 0.607 | neutral | None | None | None | None | N |
| S/I | 0.2336 | likely_benign | 0.278 | benign | -0.044 | Destabilizing | 0.062 | N | 0.677 | prob.neutral | N | 0.48731109 | None | None | N |
| S/K | 0.7234 | likely_pathogenic | 0.7793 | pathogenic | -0.512 | Destabilizing | 0.149 | N | 0.545 | neutral | None | None | None | None | N |
| S/L | 0.1341 | likely_benign | 0.1553 | benign | -0.044 | Destabilizing | 0.035 | N | 0.607 | neutral | None | None | None | None | N |
| S/M | 0.195 | likely_benign | 0.2159 | benign | 0.09 | Stabilizing | 0.555 | D | 0.611 | neutral | None | None | None | None | N |
| S/N | 0.2309 | likely_benign | 0.2685 | benign | -0.812 | Destabilizing | 0.117 | N | 0.547 | neutral | N | 0.510438054 | None | None | N |
| S/P | 0.9669 | likely_pathogenic | 0.9837 | pathogenic | -0.265 | Destabilizing | 0.262 | N | 0.605 | neutral | None | None | None | None | N |
| S/Q | 0.5846 | likely_pathogenic | 0.6245 | pathogenic | -0.833 | Destabilizing | 0.555 | D | 0.604 | neutral | None | None | None | None | N |
| S/R | 0.6147 | likely_pathogenic | 0.6889 | pathogenic | -0.619 | Destabilizing | 0.117 | N | 0.619 | neutral | N | 0.489923653 | None | None | N |
| S/T | 0.053 | likely_benign | 0.0535 | benign | -0.661 | Destabilizing | None | N | 0.189 | neutral | N | 0.458843244 | None | None | N |
| S/V | 0.2187 | likely_benign | 0.2469 | benign | -0.265 | Destabilizing | 0.035 | N | 0.601 | neutral | None | None | None | None | N |
| S/W | 0.5429 | ambiguous | 0.6429 | pathogenic | -0.903 | Destabilizing | 0.935 | D | 0.707 | prob.neutral | None | None | None | None | N |
| S/Y | 0.3024 | likely_benign | 0.3763 | ambiguous | -0.552 | Destabilizing | 0.555 | D | 0.689 | prob.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.