Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20804 | 62635;62636;62637 | chr2:178589315;178589314;178589313 | chr2:179454042;179454041;179454040 |
| N2AB | 19163 | 57712;57713;57714 | chr2:178589315;178589314;178589313 | chr2:179454042;179454041;179454040 |
| N2A | 18236 | 54931;54932;54933 | chr2:178589315;178589314;178589313 | chr2:179454042;179454041;179454040 |
| N2B | 11739 | 35440;35441;35442 | chr2:178589315;178589314;178589313 | chr2:179454042;179454041;179454040 |
| Novex-1 | 11864 | 35815;35816;35817 | chr2:178589315;178589314;178589313 | chr2:179454042;179454041;179454040 |
| Novex-2 | 11931 | 36016;36017;36018 | chr2:178589315;178589314;178589313 | chr2:179454042;179454041;179454040 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | None | None | 0.016 | N | 0.335 | 0.116 | 0.204665344411 | gnomAD-4.0.0 | 1.59303E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.02682E-05 |
| T/N | rs1218971734  |
None | 0.004 | N | 0.373 | 0.094 | 0.181679512989 | gnomAD-4.0.0 | 1.59303E-06 | None | None | None | None | N | None | 5.66701E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/P | rs760953518 |
-0.675 | 0.896 | N | 0.567 | 0.271 | 0.29132392195 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| T/P | rs760953518 |
-0.675 | 0.896 | N | 0.567 | 0.271 | 0.29132392195 | gnomAD-4.0.0 | 3.18616E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.72397E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0982 | likely_benign | 0.0905 | benign | -1.033 | Destabilizing | 0.002 | N | 0.235 | neutral | N | 0.509080167 | None | None | N |
| T/C | 0.3394 | likely_benign | 0.3549 | ambiguous | -0.685 | Destabilizing | 0.977 | D | 0.553 | neutral | None | None | None | None | N |
| T/D | 0.6194 | likely_pathogenic | 0.5809 | pathogenic | 0.133 | Stabilizing | 0.447 | N | 0.522 | neutral | None | None | None | None | N |
| T/E | 0.3811 | ambiguous | 0.3547 | ambiguous | 0.204 | Stabilizing | 0.617 | D | 0.512 | neutral | None | None | None | None | N |
| T/F | 0.2341 | likely_benign | 0.2218 | benign | -1.053 | Destabilizing | 0.85 | D | 0.578 | neutral | None | None | None | None | N |
| T/G | 0.2479 | likely_benign | 0.2294 | benign | -1.341 | Destabilizing | 0.447 | N | 0.536 | neutral | None | None | None | None | N |
| T/H | 0.266 | likely_benign | 0.2443 | benign | -1.523 | Destabilizing | 0.977 | D | 0.583 | neutral | None | None | None | None | N |
| T/I | 0.1878 | likely_benign | 0.1842 | benign | -0.284 | Destabilizing | 0.016 | N | 0.335 | neutral | N | 0.513139192 | None | None | N |
| T/K | 0.2326 | likely_benign | 0.2016 | benign | -0.439 | Destabilizing | 0.617 | D | 0.523 | neutral | None | None | None | None | N |
| T/L | 0.1017 | likely_benign | 0.1001 | benign | -0.284 | Destabilizing | 0.25 | N | 0.481 | neutral | None | None | None | None | N |
| T/M | 0.0835 | likely_benign | 0.0841 | benign | -0.168 | Destabilizing | 0.92 | D | 0.557 | neutral | None | None | None | None | N |
| T/N | 0.154 | likely_benign | 0.1488 | benign | -0.607 | Destabilizing | 0.004 | N | 0.373 | neutral | N | 0.454299762 | None | None | N |
| T/P | 0.8983 | likely_pathogenic | 0.85 | pathogenic | -0.502 | Destabilizing | 0.896 | D | 0.567 | neutral | N | 0.502118067 | None | None | N |
| T/Q | 0.1973 | likely_benign | 0.185 | benign | -0.606 | Destabilizing | 0.92 | D | 0.563 | neutral | None | None | None | None | N |
| T/R | 0.2141 | likely_benign | 0.1739 | benign | -0.439 | Destabilizing | 0.85 | D | 0.564 | neutral | None | None | None | None | N |
| T/S | 0.1082 | likely_benign | 0.1098 | benign | -1.018 | Destabilizing | 0.201 | N | 0.529 | neutral | N | 0.465366675 | None | None | N |
| T/V | 0.1319 | likely_benign | 0.1337 | benign | -0.502 | Destabilizing | 0.002 | N | 0.233 | neutral | None | None | None | None | N |
| T/W | 0.6052 | likely_pathogenic | 0.5528 | ambiguous | -0.961 | Destabilizing | 0.992 | D | 0.621 | neutral | None | None | None | None | N |
| T/Y | 0.2904 | likely_benign | 0.2634 | benign | -0.688 | Destabilizing | 0.92 | D | 0.568 | 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.