Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16025 | 48298;48299;48300 | chr2:178616816;178616815;178616814 | chr2:179481543;179481542;179481541 |
| N2AB | 14384 | 43375;43376;43377 | chr2:178616816;178616815;178616814 | chr2:179481543;179481542;179481541 |
| N2A | 13457 | 40594;40595;40596 | chr2:178616816;178616815;178616814 | chr2:179481543;179481542;179481541 |
| N2B | 6960 | 21103;21104;21105 | chr2:178616816;178616815;178616814 | chr2:179481543;179481542;179481541 |
| Novex-1 | 7085 | 21478;21479;21480 | chr2:178616816;178616815;178616814 | chr2:179481543;179481542;179481541 |
| Novex-2 | 7152 | 21679;21680;21681 | chr2:178616816;178616815;178616814 | chr2:179481543;179481542;179481541 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/N | rs727504720  |
None | 0.999 | D | 0.632 | 0.38 | 0.388010793773 | gnomAD-4.0.0 | 1.59335E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86223E-06 | 0 | 0 |
| S/R | rs1185643168 |
-0.562 | 1.0 | D | 0.739 | 0.598 | 0.460795861206 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| S/R | rs1185643168 |
-0.562 | 1.0 | D | 0.739 | 0.598 | 0.460795861206 | gnomAD-4.0.0 | 1.59335E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43332E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1091 | likely_benign | 0.1231 | benign | -1.054 | Destabilizing | 0.998 | D | 0.473 | neutral | None | None | None | None | N |
| S/C | 0.1487 | likely_benign | 0.1567 | benign | -1.244 | Destabilizing | 1.0 | D | 0.652 | neutral | N | 0.503744805 | None | None | N |
| S/D | 0.9916 | likely_pathogenic | 0.9937 | pathogenic | -2.41 | Highly Destabilizing | 0.999 | D | 0.643 | neutral | None | None | None | None | N |
| S/E | 0.9895 | likely_pathogenic | 0.9918 | pathogenic | -2.238 | Highly Destabilizing | 0.999 | D | 0.627 | neutral | None | None | None | None | N |
| S/F | 0.9799 | likely_pathogenic | 0.9836 | pathogenic | -0.848 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | N |
| S/G | 0.3613 | ambiguous | 0.3987 | ambiguous | -1.364 | Destabilizing | 0.999 | D | 0.455 | neutral | D | 0.633461606 | None | None | N |
| S/H | 0.9857 | likely_pathogenic | 0.9879 | pathogenic | -1.605 | Destabilizing | 1.0 | D | 0.676 | prob.neutral | None | None | None | None | N |
| S/I | 0.8115 | likely_pathogenic | 0.8429 | pathogenic | -0.283 | Destabilizing | 1.0 | D | 0.705 | prob.neutral | D | 0.57723822 | None | None | N |
| S/K | 0.9975 | likely_pathogenic | 0.9981 | pathogenic | -0.897 | Destabilizing | 0.999 | D | 0.639 | neutral | None | None | None | None | N |
| S/L | 0.7241 | likely_pathogenic | 0.7628 | pathogenic | -0.283 | Destabilizing | 1.0 | D | 0.696 | prob.neutral | None | None | None | None | N |
| S/M | 0.8801 | likely_pathogenic | 0.8925 | pathogenic | -0.491 | Destabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | N |
| S/N | 0.9448 | likely_pathogenic | 0.9527 | pathogenic | -1.599 | Destabilizing | 0.999 | D | 0.632 | neutral | D | 0.633461606 | None | None | N |
| S/P | 0.83 | likely_pathogenic | 0.8555 | pathogenic | -0.51 | Destabilizing | 1.0 | D | 0.74 | deleterious | None | None | None | None | N |
| S/Q | 0.9841 | likely_pathogenic | 0.9869 | pathogenic | -1.411 | Destabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | N |
| S/R | 0.9924 | likely_pathogenic | 0.9942 | pathogenic | -1.078 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | D | 0.633461606 | None | None | N |
| S/T | 0.2715 | likely_benign | 0.2881 | benign | -1.19 | Destabilizing | 0.999 | D | 0.483 | neutral | D | 0.566874343 | None | None | N |
| S/V | 0.5939 | likely_pathogenic | 0.6512 | pathogenic | -0.51 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | N |
| S/W | 0.9884 | likely_pathogenic | 0.9907 | pathogenic | -1.191 | Destabilizing | 1.0 | D | 0.639 | neutral | None | None | None | None | N |
| S/Y | 0.9788 | likely_pathogenic | 0.9826 | pathogenic | -0.771 | Destabilizing | 1.0 | D | 0.707 | prob.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.