Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23026 | 69301;69302;69303 | chr2:178577259;178577258;178577257 | chr2:179441986;179441985;179441984 |
| N2AB | 21385 | 64378;64379;64380 | chr2:178577259;178577258;178577257 | chr2:179441986;179441985;179441984 |
| N2A | 20458 | 61597;61598;61599 | chr2:178577259;178577258;178577257 | chr2:179441986;179441985;179441984 |
| N2B | 13961 | 42106;42107;42108 | chr2:178577259;178577258;178577257 | chr2:179441986;179441985;179441984 |
| Novex-1 | 14086 | 42481;42482;42483 | chr2:178577259;178577258;178577257 | chr2:179441986;179441985;179441984 |
| Novex-2 | 14153 | 42682;42683;42684 | chr2:178577259;178577258;178577257 | chr2:179441986;179441985;179441984 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/L | None | None | 0.805 | N | 0.569 | 0.39 | 0.264081493735 | gnomAD-4.0.0 | 1.36896E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79931E-06 | 0 | 0 |
| F/S | rs375365023  |
-0.35 | 0.805 | N | 0.543 | 0.431 | None | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.63E-05 | None | 0 | None | 0 | 1.78E-05 | 0 |
| F/S | rs375365023 |
-0.35 | 0.805 | N | 0.543 | 0.431 | None | gnomAD-3.1.2 | 1.98E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.42E-05 | 0 | 0 |
| F/S | rs375365023 |
-0.35 | 0.805 | N | 0.543 | 0.431 | None | gnomAD-4.0.0 | 9.92121E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 4.47748E-05 | None | 0 | 0 | 1.1022E-05 | 0 | 1.60246E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.6441 | likely_pathogenic | 0.6856 | pathogenic | -0.714 | Destabilizing | 0.033 | N | 0.544 | neutral | None | None | None | None | I |
| F/C | 0.3809 | ambiguous | 0.4085 | ambiguous | -0.244 | Destabilizing | 0.995 | D | 0.628 | neutral | D | 0.531982109 | None | None | I |
| F/D | 0.9674 | likely_pathogenic | 0.9743 | pathogenic | 0.59 | Stabilizing | 0.987 | D | 0.633 | neutral | None | None | None | None | I |
| F/E | 0.9725 | likely_pathogenic | 0.9776 | pathogenic | 0.557 | Stabilizing | 0.975 | D | 0.633 | neutral | None | None | None | None | I |
| F/G | 0.8702 | likely_pathogenic | 0.8882 | pathogenic | -0.873 | Destabilizing | 0.845 | D | 0.576 | neutral | None | None | None | None | I |
| F/H | 0.7737 | likely_pathogenic | 0.793 | pathogenic | 0.297 | Stabilizing | 0.999 | D | 0.594 | neutral | None | None | None | None | I |
| F/I | 0.5933 | likely_pathogenic | 0.6281 | pathogenic | -0.325 | Destabilizing | 0.892 | D | 0.563 | neutral | N | 0.480859855 | None | None | I |
| F/K | 0.9664 | likely_pathogenic | 0.9723 | pathogenic | -0.022 | Destabilizing | 0.975 | D | 0.635 | neutral | None | None | None | None | I |
| F/L | 0.9417 | likely_pathogenic | 0.9502 | pathogenic | -0.325 | Destabilizing | 0.805 | D | 0.569 | neutral | N | 0.464100891 | None | None | I |
| F/M | 0.7493 | likely_pathogenic | 0.7773 | pathogenic | -0.365 | Destabilizing | 0.996 | D | 0.604 | neutral | None | None | None | None | I |
| F/N | 0.8637 | likely_pathogenic | 0.8888 | pathogenic | -0.016 | Destabilizing | 0.987 | D | 0.64 | neutral | None | None | None | None | I |
| F/P | 0.9962 | likely_pathogenic | 0.9962 | pathogenic | -0.436 | Destabilizing | 0.987 | D | 0.642 | neutral | None | None | None | None | I |
| F/Q | 0.9275 | likely_pathogenic | 0.9386 | pathogenic | -0.041 | Destabilizing | 0.987 | D | 0.638 | neutral | None | None | None | None | I |
| F/R | 0.9225 | likely_pathogenic | 0.9323 | pathogenic | 0.328 | Stabilizing | 0.987 | D | 0.639 | neutral | None | None | None | None | I |
| F/S | 0.5726 | likely_pathogenic | 0.6144 | pathogenic | -0.574 | Destabilizing | 0.805 | D | 0.543 | neutral | N | 0.469277425 | None | None | I |
| F/T | 0.792 | likely_pathogenic | 0.8207 | pathogenic | -0.514 | Destabilizing | 0.975 | D | 0.537 | neutral | None | None | None | None | I |
| F/V | 0.4963 | ambiguous | 0.5232 | ambiguous | -0.436 | Destabilizing | 0.805 | D | 0.613 | neutral | N | 0.455326692 | None | None | I |
| F/W | 0.7267 | likely_pathogenic | 0.7136 | pathogenic | -0.363 | Destabilizing | 0.999 | D | 0.613 | neutral | None | None | None | None | I |
| F/Y | 0.2599 | likely_benign | 0.2536 | benign | -0.3 | Destabilizing | 0.981 | D | 0.559 | neutral | N | 0.486132389 | 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.