Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1745 | 5458;5459;5460 | chr2:178776631;178776630;178776629 | chr2:179641358;179641357;179641356 |
| N2AB | 1745 | 5458;5459;5460 | chr2:178776631;178776630;178776629 | chr2:179641358;179641357;179641356 |
| N2A | 1745 | 5458;5459;5460 | chr2:178776631;178776630;178776629 | chr2:179641358;179641357;179641356 |
| N2B | 1699 | 5320;5321;5322 | chr2:178776631;178776630;178776629 | chr2:179641358;179641357;179641356 |
| Novex-1 | 1699 | 5320;5321;5322 | chr2:178776631;178776630;178776629 | chr2:179641358;179641357;179641356 |
| Novex-2 | 1699 | 5320;5321;5322 | chr2:178776631;178776630;178776629 | chr2:179641358;179641357;179641356 |
| Novex-3 | 1745 | 5458;5459;5460 | chr2:178776631;178776630;178776629 | chr2:179641358;179641357;179641356 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/F | rs1405428231  |
-1.799 | 1.0 | D | 0.717 | 0.562 | 0.588141112584 | gnomAD-2.1.1 | 3.18E-05 | None | None | None | None | I | None | 1.14705E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| L/F | rs1405428231 |
-1.799 | 1.0 | D | 0.717 | 0.562 | 0.588141112584 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| L/F | rs1405428231 |
-1.799 | 1.0 | D | 0.717 | 0.562 | 0.588141112584 | gnomAD-4.0.0 | 6.56953E-06 | None | None | None | None | I | None | 2.41255E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| L/P | None | None | 1.0 | D | 0.862 | 0.852 | 0.895677471057 | gnomAD-4.0.0 | 5.47283E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.19436E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.9299 | likely_pathogenic | 0.9186 | pathogenic | -2.201 | Highly Destabilizing | 0.999 | D | 0.694 | prob.neutral | None | None | None | None | I |
| L/C | 0.9816 | likely_pathogenic | 0.9776 | pathogenic | -1.408 | Destabilizing | 1.0 | D | 0.772 | deleterious | None | None | None | None | I |
| L/D | 0.9992 | likely_pathogenic | 0.9991 | pathogenic | -2.025 | Highly Destabilizing | 1.0 | D | 0.855 | deleterious | None | None | None | None | I |
| L/E | 0.9918 | likely_pathogenic | 0.9908 | pathogenic | -1.915 | Destabilizing | 1.0 | D | 0.86 | deleterious | None | None | None | None | I |
| L/F | 0.8447 | likely_pathogenic | 0.8215 | pathogenic | -1.441 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | D | 0.620528145 | None | None | I |
| L/G | 0.9942 | likely_pathogenic | 0.9929 | pathogenic | -2.61 | Highly Destabilizing | 1.0 | D | 0.859 | deleterious | None | None | None | None | I |
| L/H | 0.991 | likely_pathogenic | 0.9897 | pathogenic | -1.734 | Destabilizing | 1.0 | D | 0.845 | deleterious | D | 0.773907517 | None | None | I |
| L/I | 0.2677 | likely_benign | 0.2545 | benign | -1.078 | Destabilizing | 0.999 | D | 0.526 | neutral | N | 0.482295874 | None | None | I |
| L/K | 0.9846 | likely_pathogenic | 0.9846 | pathogenic | -1.709 | Destabilizing | 1.0 | D | 0.829 | deleterious | None | None | None | None | I |
| L/M | 0.4161 | ambiguous | 0.3977 | ambiguous | -0.926 | Destabilizing | 1.0 | D | 0.742 | deleterious | None | None | None | None | I |
| L/N | 0.9959 | likely_pathogenic | 0.9952 | pathogenic | -1.722 | Destabilizing | 1.0 | D | 0.86 | deleterious | None | None | None | None | I |
| L/P | 0.9882 | likely_pathogenic | 0.9891 | pathogenic | -1.428 | Destabilizing | 1.0 | D | 0.862 | deleterious | D | 0.737296303 | None | None | I |
| L/Q | 0.973 | likely_pathogenic | 0.9696 | pathogenic | -1.767 | Destabilizing | 1.0 | D | 0.846 | deleterious | None | None | None | None | I |
| L/R | 0.9756 | likely_pathogenic | 0.975 | pathogenic | -1.201 | Destabilizing | 1.0 | D | 0.851 | deleterious | D | 0.773503018 | None | None | I |
| L/S | 0.9905 | likely_pathogenic | 0.9887 | pathogenic | -2.333 | Highly Destabilizing | 1.0 | D | 0.819 | deleterious | None | None | None | None | I |
| L/T | 0.945 | likely_pathogenic | 0.9357 | pathogenic | -2.088 | Highly Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | I |
| L/V | 0.3239 | likely_benign | 0.299 | benign | -1.428 | Destabilizing | 0.999 | D | 0.513 | neutral | N | 0.513348375 | None | None | I |
| L/W | 0.9746 | likely_pathogenic | 0.9722 | pathogenic | -1.579 | Destabilizing | 1.0 | D | 0.78 | deleterious | None | None | None | None | I |
| L/Y | 0.9863 | likely_pathogenic | 0.9837 | pathogenic | -1.363 | Destabilizing | 1.0 | D | 0.827 | deleterious | None | None | None | None | I |
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.