Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1921 | 5986;5987;5988 | chr2:178776103;178776102;178776101 | chr2:179640830;179640829;179640828 |
| N2AB | 1921 | 5986;5987;5988 | chr2:178776103;178776102;178776101 | chr2:179640830;179640829;179640828 |
| N2A | 1921 | 5986;5987;5988 | chr2:178776103;178776102;178776101 | chr2:179640830;179640829;179640828 |
| N2B | 1875 | 5848;5849;5850 | chr2:178776103;178776102;178776101 | chr2:179640830;179640829;179640828 |
| Novex-1 | 1875 | 5848;5849;5850 | chr2:178776103;178776102;178776101 | chr2:179640830;179640829;179640828 |
| Novex-2 | 1875 | 5848;5849;5850 | chr2:178776103;178776102;178776101 | chr2:179640830;179640829;179640828 |
| Novex-3 | 1921 | 5986;5987;5988 | chr2:178776103;178776102;178776101 | chr2:179640830;179640829;179640828 |
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/V | rs879100565  |
-0.953 | None | N | 0.096 | 0.112 | 0.223146558224 | gnomAD-2.1.1 | 7.08E-06 | None | None | None | None | I | None | 4.01E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 7.76E-06 | 0 |
| I/V | rs879100565 |
-0.953 | None | N | 0.096 | 0.112 | 0.223146558224 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/V | rs879100565 |
-0.953 | None | N | 0.096 | 0.112 | 0.223146558224 | gnomAD-4.0.0 | 1.54892E-05 | None | None | None | None | I | None | 2.66944E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.86442E-05 | 0 | 1.60041E-05 |
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 | 0.12 | likely_benign | 0.1152 | benign | -1.413 | Destabilizing | None | N | 0.127 | neutral | None | None | None | None | I |
| I/C | 0.5882 | likely_pathogenic | 0.5253 | ambiguous | -0.764 | Destabilizing | 0.245 | N | 0.433 | neutral | None | None | None | None | I |
| I/D | 0.6843 | likely_pathogenic | 0.6657 | pathogenic | -1.081 | Destabilizing | 0.044 | N | 0.515 | neutral | None | None | None | None | I |
| I/E | 0.462 | ambiguous | 0.4548 | ambiguous | -1.111 | Destabilizing | 0.018 | N | 0.45 | neutral | None | None | None | None | I |
| I/F | 0.2491 | likely_benign | 0.2348 | benign | -1.046 | Destabilizing | 0.044 | N | 0.373 | neutral | None | None | None | None | I |
| I/G | 0.5685 | likely_pathogenic | 0.5353 | ambiguous | -1.695 | Destabilizing | 0.009 | N | 0.451 | neutral | None | None | None | None | I |
| I/H | 0.5536 | ambiguous | 0.5344 | ambiguous | -0.932 | Destabilizing | 0.497 | N | 0.533 | neutral | None | None | None | None | I |
| I/K | 0.3252 | likely_benign | 0.3516 | ambiguous | -1.029 | Destabilizing | 0.014 | N | 0.447 | neutral | N | 0.49993976 | None | None | I |
| I/L | 0.1196 | likely_benign | 0.1144 | benign | -0.73 | Destabilizing | None | N | 0.265 | neutral | N | 0.48408601 | None | None | I |
| I/M | 0.0802 | likely_benign | 0.0786 | benign | -0.544 | Destabilizing | None | N | 0.268 | neutral | N | 0.510080743 | None | None | I |
| I/N | 0.2999 | likely_benign | 0.288 | benign | -0.803 | Destabilizing | 0.044 | N | 0.554 | neutral | None | None | None | None | I |
| I/P | 0.9343 | likely_pathogenic | 0.951 | pathogenic | -0.926 | Destabilizing | 0.085 | N | 0.571 | neutral | None | None | None | None | I |
| I/Q | 0.3308 | likely_benign | 0.3388 | benign | -1.021 | Destabilizing | 0.085 | N | 0.599 | neutral | None | None | None | None | I |
| I/R | 0.2671 | likely_benign | 0.2929 | benign | -0.381 | Destabilizing | 0.033 | N | 0.57 | neutral | N | 0.494199326 | None | None | I |
| I/S | 0.1893 | likely_benign | 0.1765 | benign | -1.302 | Destabilizing | 0.001 | N | 0.197 | neutral | None | None | None | None | I |
| I/T | 0.0626 | likely_benign | 0.063 | benign | -1.224 | Destabilizing | None | N | 0.13 | neutral | N | 0.454582937 | None | None | I |
| I/V | 0.0709 | likely_benign | 0.0666 | benign | -0.926 | Destabilizing | None | N | 0.096 | neutral | N | 0.392069561 | None | None | I |
| I/W | 0.8076 | likely_pathogenic | 0.7932 | pathogenic | -1.115 | Destabilizing | 0.788 | D | 0.519 | neutral | None | None | None | None | I |
| I/Y | 0.6389 | likely_pathogenic | 0.6199 | pathogenic | -0.897 | Destabilizing | 0.245 | N | 0.513 | neutral | 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.