Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29504 | 88735;88736;88737 | chr2:178554949;178554948;178554947 | chr2:179419676;179419675;179419674 |
| N2AB | 27863 | 83812;83813;83814 | chr2:178554949;178554948;178554947 | chr2:179419676;179419675;179419674 |
| N2A | 26936 | 81031;81032;81033 | chr2:178554949;178554948;178554947 | chr2:179419676;179419675;179419674 |
| N2B | 20439 | 61540;61541;61542 | chr2:178554949;178554948;178554947 | chr2:179419676;179419675;179419674 |
| Novex-1 | 20564 | 61915;61916;61917 | chr2:178554949;178554948;178554947 | chr2:179419676;179419675;179419674 |
| Novex-2 | 20631 | 62116;62117;62118 | chr2:178554949;178554948;178554947 | chr2:179419676;179419675;179419674 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | None | None | 0.003 | N | 0.205 | 0.103 | 0.0716867268079 | gnomAD-4.0.0 | 8.40227E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.18751E-06 | 0 | 0 |
| D/N | rs376679796  |
0.136 | None | N | 0.11 | 0.099 | None | gnomAD-2.1.1 | 6.78989E-04 | None | None | None | None | N | None | 1.65317E-04 | 1.98267E-04 | None | 0 | 0 | None | 5.00033E-03 | None | 1.20096E-04 | 1.56389E-04 | 4.21348E-04 |
| D/N | rs376679796 |
0.136 | None | N | 0.11 | 0.099 | None | gnomAD-3.1.2 | 2.23464E-04 | None | None | None | None | N | None | 1.68911E-04 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 8.82E-05 | 4.14422E-03 | 0 |
| D/N | rs376679796 |
0.136 | None | N | 0.11 | 0.099 | None | 1000 genomes | 9.98403E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 5.1E-03 | None |
| D/N | rs376679796 |
0.136 | None | N | 0.11 | 0.099 | None | gnomAD-4.0.0 | 3.51971E-04 | None | None | None | None | N | None | 1.99893E-04 | 1.83291E-04 | None | 0 | 8.92977E-05 | None | 2.18812E-04 | 8.25083E-04 | 7.20451E-05 | 4.54575E-03 | 3.20123E-04 |
| D/Y | None | None | 0.383 | D | 0.453 | 0.112 | 0.511390160789 | gnomAD-4.0.0 | 3.42114E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.49722E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.0937 | likely_benign | 0.0862 | benign | -0.468 | Destabilizing | 0.001 | N | 0.204 | neutral | N | 0.494693157 | None | None | N |
| D/C | 0.2423 | likely_benign | 0.2227 | benign | -0.033 | Destabilizing | None | N | 0.214 | neutral | None | None | None | None | N |
| D/E | 0.1469 | likely_benign | 0.1406 | benign | -0.524 | Destabilizing | 0.003 | N | 0.205 | neutral | N | 0.442589468 | None | None | N |
| D/F | 0.3758 | ambiguous | 0.3565 | ambiguous | -0.407 | Destabilizing | 0.085 | N | 0.437 | neutral | None | None | None | None | N |
| D/G | 0.0974 | likely_benign | 0.0925 | benign | -0.718 | Destabilizing | 0.003 | N | 0.219 | neutral | N | 0.514415068 | None | None | N |
| D/H | 0.1321 | likely_benign | 0.1245 | benign | -0.536 | Destabilizing | 0.235 | N | 0.33 | neutral | N | 0.489980771 | None | None | N |
| D/I | 0.1869 | likely_benign | 0.1735 | benign | 0.161 | Stabilizing | 0.022 | N | 0.421 | neutral | None | None | None | None | N |
| D/K | 0.169 | likely_benign | 0.158 | benign | -0.067 | Destabilizing | 0.009 | N | 0.342 | neutral | None | None | None | None | N |
| D/L | 0.1849 | likely_benign | 0.173 | benign | 0.161 | Stabilizing | 0.009 | N | 0.347 | neutral | None | None | None | None | N |
| D/M | 0.3069 | likely_benign | 0.2834 | benign | 0.498 | Stabilizing | 0.245 | N | 0.4 | neutral | None | None | None | None | N |
| D/N | 0.0546 | likely_benign | 0.0551 | benign | -0.35 | Destabilizing | None | N | 0.11 | neutral | N | 0.467487913 | None | None | N |
| D/P | 0.5925 | likely_pathogenic | 0.5982 | pathogenic | -0.025 | Destabilizing | 0.085 | N | 0.343 | neutral | None | None | None | None | N |
| D/Q | 0.1755 | likely_benign | 0.1629 | benign | -0.294 | Destabilizing | 0.044 | N | 0.163 | neutral | None | None | None | None | N |
| D/R | 0.1893 | likely_benign | 0.1738 | benign | 0.063 | Stabilizing | 0.044 | N | 0.389 | neutral | None | None | None | None | N |
| D/S | 0.0589 | likely_benign | 0.0565 | benign | -0.5 | Destabilizing | None | N | 0.103 | neutral | None | None | None | None | N |
| D/T | 0.0854 | likely_benign | 0.0739 | benign | -0.309 | Destabilizing | None | N | 0.115 | neutral | None | None | None | None | N |
| D/V | 0.128 | likely_benign | 0.1179 | benign | -0.025 | Destabilizing | 0.007 | N | 0.351 | neutral | N | 0.462236809 | None | None | N |
| D/W | 0.7075 | likely_pathogenic | 0.6739 | pathogenic | -0.283 | Destabilizing | 0.788 | D | 0.388 | neutral | None | None | None | None | N |
| D/Y | 0.1445 | likely_benign | 0.1413 | benign | -0.189 | Destabilizing | 0.383 | N | 0.453 | neutral | D | 0.533520904 | 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.