Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31194 | 93805;93806;93807 | chr2:178548046;178548045;178548044 | chr2:179412773;179412772;179412771 |
| N2AB | 29553 | 88882;88883;88884 | chr2:178548046;178548045;178548044 | chr2:179412773;179412772;179412771 |
| N2A | 28626 | 86101;86102;86103 | chr2:178548046;178548045;178548044 | chr2:179412773;179412772;179412771 |
| N2B | 22129 | 66610;66611;66612 | chr2:178548046;178548045;178548044 | chr2:179412773;179412772;179412771 |
| Novex-1 | 22254 | 66985;66986;66987 | chr2:178548046;178548045;178548044 | chr2:179412773;179412772;179412771 |
| Novex-2 | 22321 | 67186;67187;67188 | chr2:178548046;178548045;178548044 | chr2:179412773;179412772;179412771 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/C | rs543223589  |
-0.398 | 0.009 | N | 0.437 | 0.235 | 0.286465849087 | gnomAD-2.1.1 | 4.64E-05 | None | None | None | None | N | None | 4.13E-05 | 1.41435E-04 | None | 0 | 0 | None | 1.30727E-04 | None | 0 | 2.34E-05 | 0 |
| Y/C | rs543223589 |
-0.398 | 0.009 | N | 0.437 | 0.235 | 0.286465849087 | gnomAD-3.1.2 | 3.94E-05 | None | None | None | None | N | None | 2.41E-05 | 1.96541E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 4.14422E-04 | 0 |
| Y/C | rs543223589 |
-0.398 | 0.009 | N | 0.437 | 0.235 | 0.286465849087 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| Y/C | rs543223589 |
-0.398 | 0.009 | N | 0.437 | 0.235 | 0.286465849087 | gnomAD-4.0.0 | 2.04475E-05 | None | None | None | None | N | None | 1.33255E-05 | 1.83339E-04 | None | 0 | 0 | None | 0 | 0 | 9.32347E-06 | 8.78349E-05 | 3.20082E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.31 | likely_benign | 0.3246 | benign | -1.915 | Destabilizing | 0.25 | N | 0.539 | neutral | None | None | None | None | N |
| Y/C | 0.0909 | likely_benign | 0.1027 | benign | -0.72 | Destabilizing | 0.009 | N | 0.437 | neutral | N | 0.457947631 | None | None | N |
| Y/D | 0.1882 | likely_benign | 0.1817 | benign | 0.172 | Stabilizing | 0.963 | D | 0.571 | neutral | N | 0.43926587 | None | None | N |
| Y/E | 0.4379 | ambiguous | 0.4355 | ambiguous | 0.237 | Stabilizing | 0.972 | D | 0.551 | neutral | None | None | None | None | N |
| Y/F | 0.0768 | likely_benign | 0.083 | benign | -0.869 | Destabilizing | 0.712 | D | 0.42 | neutral | N | 0.420680109 | None | None | N |
| Y/G | 0.3857 | ambiguous | 0.3872 | ambiguous | -2.205 | Highly Destabilizing | 0.617 | D | 0.563 | neutral | None | None | None | None | N |
| Y/H | 0.178 | likely_benign | 0.1888 | benign | -0.585 | Destabilizing | 0.963 | D | 0.558 | neutral | N | 0.471474289 | None | None | N |
| Y/I | 0.2163 | likely_benign | 0.2253 | benign | -1.068 | Destabilizing | 0.009 | N | 0.297 | neutral | None | None | None | None | N |
| Y/K | 0.5012 | ambiguous | 0.5121 | ambiguous | -0.688 | Destabilizing | 0.92 | D | 0.55 | neutral | None | None | None | None | N |
| Y/L | 0.2311 | likely_benign | 0.2506 | benign | -1.068 | Destabilizing | 0.127 | N | 0.369 | neutral | None | None | None | None | N |
| Y/M | 0.3929 | ambiguous | 0.4126 | ambiguous | -0.776 | Destabilizing | 0.92 | D | 0.543 | neutral | None | None | None | None | N |
| Y/N | 0.1277 | likely_benign | 0.1448 | benign | -0.922 | Destabilizing | 0.963 | D | 0.573 | neutral | N | 0.43926587 | None | None | N |
| Y/P | 0.5147 | ambiguous | 0.5164 | ambiguous | -1.34 | Destabilizing | 0.972 | D | 0.585 | neutral | None | None | None | None | N |
| Y/Q | 0.393 | ambiguous | 0.4258 | ambiguous | -0.854 | Destabilizing | 0.972 | D | 0.55 | neutral | None | None | None | None | N |
| Y/R | 0.3878 | ambiguous | 0.4119 | ambiguous | -0.269 | Destabilizing | 0.972 | D | 0.573 | neutral | None | None | None | None | N |
| Y/S | 0.1528 | likely_benign | 0.1584 | benign | -1.58 | Destabilizing | 0.549 | D | 0.564 | neutral | N | 0.417735804 | None | None | N |
| Y/T | 0.2738 | likely_benign | 0.2834 | benign | -1.419 | Destabilizing | 0.617 | D | 0.519 | neutral | None | None | None | None | N |
| Y/V | 0.1862 | likely_benign | 0.1891 | benign | -1.34 | Destabilizing | 0.009 | N | 0.301 | neutral | None | None | None | None | N |
| Y/W | 0.3619 | ambiguous | 0.3573 | ambiguous | -0.532 | Destabilizing | 0.992 | D | 0.561 | 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.