Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27944 | 84055;84056;84057 | chr2:178562302;178562301;178562300 | chr2:179427029;179427028;179427027 |
| N2AB | 26303 | 79132;79133;79134 | chr2:178562302;178562301;178562300 | chr2:179427029;179427028;179427027 |
| N2A | 25376 | 76351;76352;76353 | chr2:178562302;178562301;178562300 | chr2:179427029;179427028;179427027 |
| N2B | 18879 | 56860;56861;56862 | chr2:178562302;178562301;178562300 | chr2:179427029;179427028;179427027 |
| Novex-1 | 19004 | 57235;57236;57237 | chr2:178562302;178562301;178562300 | chr2:179427029;179427028;179427027 |
| Novex-2 | 19071 | 57436;57437;57438 | chr2:178562302;178562301;178562300 | chr2:179427029;179427028;179427027 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/I | rs773829475  |
0.288 | 0.295 | N | 0.517 | 0.15 | 0.373715746628 | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.11732E-04 | None | 0 | None | 0 | 0 | 0 |
| R/I | rs773829475 |
0.288 | 0.295 | N | 0.517 | 0.15 | 0.373715746628 | gnomAD-4.0.0 | 3.1847E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.55216E-05 | None | 0 | 0 | 0 | 0 | 0 |
| R/K | rs773829475 |
-0.128 | None | N | 0.215 | 0.106 | 0.126345400529 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| R/K | rs773829475 |
-0.128 | None | N | 0.215 | 0.106 | 0.126345400529 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.06868E-04 | 0 |
| R/K | rs773829475 |
-0.128 | None | N | 0.215 | 0.106 | 0.126345400529 | gnomAD-4.0.0 | 2.5635E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.39367E-06 | 1.34149E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.1824 | likely_benign | 0.2778 | benign | -0.446 | Destabilizing | 0.007 | N | 0.413 | neutral | None | None | None | None | N |
| R/C | 0.1216 | likely_benign | 0.153 | benign | -0.536 | Destabilizing | 0.864 | D | 0.515 | neutral | None | None | None | None | N |
| R/D | 0.4916 | ambiguous | 0.651 | pathogenic | 0.045 | Stabilizing | 0.016 | N | 0.509 | neutral | None | None | None | None | N |
| R/E | 0.2001 | likely_benign | 0.3 | benign | 0.116 | Stabilizing | None | N | 0.253 | neutral | None | None | None | None | N |
| R/F | 0.2439 | likely_benign | 0.3497 | ambiguous | -0.631 | Destabilizing | 0.628 | D | 0.519 | neutral | None | None | None | None | N |
| R/G | 0.1621 | likely_benign | 0.248 | benign | -0.659 | Destabilizing | 0.024 | N | 0.497 | neutral | N | 0.510645965 | None | None | N |
| R/H | 0.0943 | likely_benign | 0.1077 | benign | -0.971 | Destabilizing | 0.214 | N | 0.505 | neutral | None | None | None | None | N |
| R/I | 0.1097 | likely_benign | 0.1504 | benign | 0.09 | Stabilizing | 0.295 | N | 0.517 | neutral | N | 0.412809987 | None | None | N |
| R/K | 0.0585 | likely_benign | 0.0693 | benign | -0.397 | Destabilizing | None | N | 0.215 | neutral | N | 0.414407498 | None | None | N |
| R/L | 0.1078 | likely_benign | 0.1568 | benign | 0.09 | Stabilizing | 0.031 | N | 0.491 | neutral | None | None | None | None | N |
| R/M | 0.1217 | likely_benign | 0.1657 | benign | -0.204 | Destabilizing | 0.356 | N | 0.503 | neutral | None | None | None | None | N |
| R/N | 0.302 | likely_benign | 0.4407 | ambiguous | -0.029 | Destabilizing | 0.031 | N | 0.372 | neutral | None | None | None | None | N |
| R/P | 0.2945 | likely_benign | 0.4581 | ambiguous | -0.068 | Destabilizing | 0.136 | N | 0.494 | neutral | None | None | None | None | N |
| R/Q | 0.0796 | likely_benign | 0.093 | benign | -0.229 | Destabilizing | None | N | 0.264 | neutral | None | None | None | None | N |
| R/S | 0.2442 | likely_benign | 0.3762 | ambiguous | -0.649 | Destabilizing | 0.012 | N | 0.469 | neutral | N | 0.475762601 | None | None | N |
| R/T | 0.1152 | likely_benign | 0.1629 | benign | -0.43 | Destabilizing | 0.024 | N | 0.446 | neutral | N | 0.431665107 | None | None | N |
| R/V | 0.1391 | likely_benign | 0.1973 | benign | -0.068 | Destabilizing | 0.072 | N | 0.519 | neutral | None | None | None | None | N |
| R/W | 0.1234 | likely_benign | 0.1562 | benign | -0.504 | Destabilizing | 0.864 | D | 0.523 | neutral | None | None | None | None | N |
| R/Y | 0.1922 | likely_benign | 0.2611 | benign | -0.131 | Destabilizing | 0.356 | N | 0.521 | 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.