Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18102 | 54529;54530;54531 | chr2:178604785;178604784;178604783 | chr2:179469512;179469511;179469510 |
| N2AB | 16461 | 49606;49607;49608 | chr2:178604785;178604784;178604783 | chr2:179469512;179469511;179469510 |
| N2A | 15534 | 46825;46826;46827 | chr2:178604785;178604784;178604783 | chr2:179469512;179469511;179469510 |
| N2B | 9037 | 27334;27335;27336 | chr2:178604785;178604784;178604783 | chr2:179469512;179469511;179469510 |
| Novex-1 | 9162 | 27709;27710;27711 | chr2:178604785;178604784;178604783 | chr2:179469512;179469511;179469510 |
| Novex-2 | 9229 | 27910;27911;27912 | chr2:178604785;178604784;178604783 | chr2:179469512;179469511;179469510 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/N | rs1318872584  |
None | 0.963 | D | 0.866 | 0.566 | 0.877393276936 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/N | rs1318872584 |
None | 0.963 | D | 0.866 | 0.566 | 0.877393276936 | gnomAD-4.0.0 | 6.58137E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47193E-05 | 0 | 0 |
| I/T | rs1318872584 |
-3.333 | 0.549 | D | 0.655 | 0.451 | 0.706496497531 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 5.81E-05 | None | 0 | 5.61E-05 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs1318872584 |
-3.333 | 0.549 | D | 0.655 | 0.451 | 0.706496497531 | gnomAD-4.0.0 | 7.97151E-06 | None | None | None | None | N | None | 0 | 4.57896E-05 | None | 4.77646E-05 | 0 | None | 0 | 0 | 5.72813E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.9133 | likely_pathogenic | 0.9237 | pathogenic | -2.789 | Highly Destabilizing | 0.25 | N | 0.655 | neutral | None | None | None | None | N |
| I/C | 0.9653 | likely_pathogenic | 0.9699 | pathogenic | -2.155 | Highly Destabilizing | 0.977 | D | 0.785 | deleterious | None | None | None | None | N |
| I/D | 0.9996 | likely_pathogenic | 0.9997 | pathogenic | -3.599 | Highly Destabilizing | 0.972 | D | 0.856 | deleterious | None | None | None | None | N |
| I/E | 0.9982 | likely_pathogenic | 0.9985 | pathogenic | -3.275 | Highly Destabilizing | 0.92 | D | 0.818 | deleterious | None | None | None | None | N |
| I/F | 0.7409 | likely_pathogenic | 0.778 | pathogenic | -1.66 | Destabilizing | 0.81 | D | 0.655 | neutral | D | 0.527404567 | None | None | N |
| I/G | 0.9952 | likely_pathogenic | 0.9962 | pathogenic | -3.4 | Highly Destabilizing | 0.92 | D | 0.807 | deleterious | None | None | None | None | N |
| I/H | 0.9982 | likely_pathogenic | 0.9986 | pathogenic | -3.157 | Highly Destabilizing | 0.992 | D | 0.867 | deleterious | None | None | None | None | N |
| I/K | 0.9967 | likely_pathogenic | 0.997 | pathogenic | -2.135 | Highly Destabilizing | 0.92 | D | 0.815 | deleterious | None | None | None | None | N |
| I/L | 0.2674 | likely_benign | 0.2798 | benign | -0.944 | Destabilizing | 0.002 | N | 0.258 | neutral | N | 0.49145249 | None | None | N |
| I/M | 0.3419 | ambiguous | 0.3657 | ambiguous | -1.24 | Destabilizing | 0.81 | D | 0.61 | neutral | N | 0.504273883 | None | None | N |
| I/N | 0.9951 | likely_pathogenic | 0.9963 | pathogenic | -2.876 | Highly Destabilizing | 0.963 | D | 0.866 | deleterious | D | 0.527658057 | None | None | N |
| I/P | 0.9975 | likely_pathogenic | 0.9975 | pathogenic | -1.551 | Destabilizing | 0.972 | D | 0.859 | deleterious | None | None | None | None | N |
| I/Q | 0.9966 | likely_pathogenic | 0.997 | pathogenic | -2.516 | Highly Destabilizing | 0.972 | D | 0.865 | deleterious | None | None | None | None | N |
| I/R | 0.9943 | likely_pathogenic | 0.9948 | pathogenic | -2.197 | Highly Destabilizing | 0.92 | D | 0.865 | deleterious | None | None | None | None | N |
| I/S | 0.9845 | likely_pathogenic | 0.9867 | pathogenic | -3.408 | Highly Destabilizing | 0.81 | D | 0.773 | deleterious | D | 0.527658057 | None | None | N |
| I/T | 0.8528 | likely_pathogenic | 0.8643 | pathogenic | -2.918 | Highly Destabilizing | 0.549 | D | 0.655 | neutral | D | 0.527404567 | None | None | N |
| I/V | 0.1111 | likely_benign | 0.122 | benign | -1.551 | Destabilizing | 0.001 | N | 0.205 | neutral | N | 0.424699062 | None | None | N |
| I/W | 0.9955 | likely_pathogenic | 0.9953 | pathogenic | -2.1 | Highly Destabilizing | 0.992 | D | 0.857 | deleterious | None | None | None | None | N |
| I/Y | 0.9883 | likely_pathogenic | 0.9904 | pathogenic | -1.9 | Destabilizing | 0.92 | D | 0.759 | deleterious | 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.