Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 10086 | 30481;30482;30483 | chr2:178702631;178702630;178702629 | chr2:179567358;179567357;179567356 |
| N2AB | 9769 | 29530;29531;29532 | chr2:178702631;178702630;178702629 | chr2:179567358;179567357;179567356 |
| N2A | 8842 | 26749;26750;26751 | chr2:178702631;178702630;178702629 | chr2:179567358;179567357;179567356 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/D | rs1188623443  |
0.208 | 0.98 | None | 0.421 | 0.34 | 0.250579442822 | gnomAD-2.1.1 | 4.01E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.65344E-04 |
| N/D | rs1188623443 |
0.208 | 0.98 | None | 0.421 | 0.34 | 0.250579442822 | gnomAD-4.0.0 | 1.59091E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.02352E-05 |
| N/K | rs2075205547 |
None | 0.98 | None | 0.423 | 0.377 | 0.307016933798 | gnomAD-4.0.0 | 1.59088E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85753E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.9542 | likely_pathogenic | 0.973 | pathogenic | -0.778 | Destabilizing | 0.971 | D | 0.486 | neutral | None | None | None | None | N |
| N/C | 0.9786 | likely_pathogenic | 0.9893 | pathogenic | 0.023 | Stabilizing | 1.0 | D | 0.667 | neutral | None | None | None | None | N |
| N/D | 0.6484 | likely_pathogenic | 0.6361 | pathogenic | -0.182 | Destabilizing | 0.98 | D | 0.421 | neutral | None | None | None | None | N |
| N/E | 0.9748 | likely_pathogenic | 0.9792 | pathogenic | -0.071 | Destabilizing | 0.985 | D | 0.417 | neutral | None | None | None | None | N |
| N/F | 0.9979 | likely_pathogenic | 0.9991 | pathogenic | -0.555 | Destabilizing | 0.999 | D | 0.69 | prob.neutral | None | None | None | None | N |
| N/G | 0.9255 | likely_pathogenic | 0.9336 | pathogenic | -1.111 | Destabilizing | 0.985 | D | 0.411 | neutral | None | None | None | None | N |
| N/H | 0.821 | likely_pathogenic | 0.8557 | pathogenic | -0.717 | Destabilizing | 0.999 | D | 0.472 | neutral | None | None | None | None | N |
| N/I | 0.9916 | likely_pathogenic | 0.9968 | pathogenic | 0.07 | Stabilizing | 0.994 | D | 0.674 | neutral | None | None | None | None | N |
| N/K | 0.9863 | likely_pathogenic | 0.9898 | pathogenic | -0.124 | Destabilizing | 0.98 | D | 0.423 | neutral | None | None | None | None | N |
| N/L | 0.9823 | likely_pathogenic | 0.9924 | pathogenic | 0.07 | Stabilizing | 0.996 | D | 0.583 | neutral | None | None | None | None | N |
| N/M | 0.9879 | likely_pathogenic | 0.9947 | pathogenic | 0.245 | Stabilizing | 1.0 | D | 0.631 | neutral | None | None | None | None | N |
| N/P | 0.9166 | likely_pathogenic | 0.9376 | pathogenic | -0.184 | Destabilizing | 0.998 | D | 0.657 | neutral | None | None | None | None | N |
| N/Q | 0.9782 | likely_pathogenic | 0.9845 | pathogenic | -0.575 | Destabilizing | 0.998 | D | 0.471 | neutral | None | None | None | None | N |
| N/R | 0.9864 | likely_pathogenic | 0.9902 | pathogenic | -0.165 | Destabilizing | 0.998 | D | 0.465 | neutral | None | None | None | None | N |
| N/S | 0.5173 | ambiguous | 0.5793 | pathogenic | -0.762 | Destabilizing | 0.659 | D | 0.249 | neutral | None | None | None | None | N |
| N/T | 0.8863 | likely_pathogenic | 0.9325 | pathogenic | -0.456 | Destabilizing | 0.4 | N | 0.264 | neutral | None | None | None | None | N |
| N/V | 0.9861 | likely_pathogenic | 0.9945 | pathogenic | -0.184 | Destabilizing | 0.996 | D | 0.587 | neutral | None | None | None | None | N |
| N/W | 0.9983 | likely_pathogenic | 0.9992 | pathogenic | -0.371 | Destabilizing | 1.0 | D | 0.654 | neutral | None | None | None | None | N |
| N/Y | 0.9461 | likely_pathogenic | 0.9687 | pathogenic | -0.133 | Destabilizing | 0.999 | D | 0.669 | 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.