Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1541 | 4846;4847;4848 | chr2:178777444;178777443;178777442 | chr2:179642171;179642170;179642169 |
| N2AB | 1541 | 4846;4847;4848 | chr2:178777444;178777443;178777442 | chr2:179642171;179642170;179642169 |
| N2A | 1541 | 4846;4847;4848 | chr2:178777444;178777443;178777442 | chr2:179642171;179642170;179642169 |
| N2B | 1495 | 4708;4709;4710 | chr2:178777444;178777443;178777442 | chr2:179642171;179642170;179642169 |
| Novex-1 | 1495 | 4708;4709;4710 | chr2:178777444;178777443;178777442 | chr2:179642171;179642170;179642169 |
| Novex-2 | 1495 | 4708;4709;4710 | chr2:178777444;178777443;178777442 | chr2:179642171;179642170;179642169 |
| Novex-3 | 1541 | 4846;4847;4848 | chr2:178777444;178777443;178777442 | chr2:179642171;179642170;179642169 |
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/M | None | None | 0.984 | N | 0.6 | 0.349 | 0.531629458225 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.625E-06 | 0 | 0 |
| I/T | rs1293333289  |
-1.04 | 0.896 | N | 0.566 | 0.533 | 0.703335290885 | gnomAD-2.1.1 | 4E-06 | None | None | None | None | I | None | 6.19E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs1293333289 |
-1.04 | 0.896 | N | 0.566 | 0.533 | 0.703335290885 | gnomAD-4.0.0 | 3.18263E-06 | None | None | None | None | I | None | 1.13122E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 | 0.4516 | ambiguous | 0.4641 | ambiguous | -1.755 | Destabilizing | 0.702 | D | 0.534 | neutral | None | None | None | None | I |
| I/C | 0.7685 | likely_pathogenic | 0.7872 | pathogenic | -1.406 | Destabilizing | 0.999 | D | 0.661 | neutral | None | None | None | None | I |
| I/D | 0.9143 | likely_pathogenic | 0.9136 | pathogenic | -0.739 | Destabilizing | 0.996 | D | 0.767 | deleterious | None | None | None | None | I |
| I/E | 0.8252 | likely_pathogenic | 0.825 | pathogenic | -0.633 | Destabilizing | 0.988 | D | 0.753 | deleterious | None | None | None | None | I |
| I/F | 0.3037 | likely_benign | 0.3158 | benign | -0.99 | Destabilizing | 0.984 | D | 0.572 | neutral | N | 0.425145206 | None | None | I |
| I/G | 0.8526 | likely_pathogenic | 0.8558 | pathogenic | -2.175 | Highly Destabilizing | 0.988 | D | 0.727 | prob.delet. | None | None | None | None | I |
| I/H | 0.7653 | likely_pathogenic | 0.7749 | pathogenic | -1.287 | Destabilizing | 0.999 | D | 0.752 | deleterious | None | None | None | None | I |
| I/K | 0.758 | likely_pathogenic | 0.7482 | pathogenic | -1.157 | Destabilizing | 0.988 | D | 0.755 | deleterious | None | None | None | None | I |
| I/L | 0.1647 | likely_benign | 0.17 | benign | -0.63 | Destabilizing | 0.437 | N | 0.315 | neutral | N | 0.482006266 | None | None | I |
| I/M | 0.153 | likely_benign | 0.156 | benign | -0.738 | Destabilizing | 0.984 | D | 0.6 | neutral | N | 0.507774618 | None | None | I |
| I/N | 0.5678 | likely_pathogenic | 0.5606 | ambiguous | -1.206 | Destabilizing | 0.995 | D | 0.764 | deleterious | N | 0.464631586 | None | None | I |
| I/P | 0.9872 | likely_pathogenic | 0.9864 | pathogenic | -0.976 | Destabilizing | 0.996 | D | 0.766 | deleterious | None | None | None | None | I |
| I/Q | 0.7061 | likely_pathogenic | 0.711 | pathogenic | -1.179 | Destabilizing | 0.996 | D | 0.768 | deleterious | None | None | None | None | I |
| I/R | 0.6777 | likely_pathogenic | 0.667 | pathogenic | -0.796 | Destabilizing | 0.988 | D | 0.767 | deleterious | None | None | None | None | I |
| I/S | 0.5004 | ambiguous | 0.4979 | ambiguous | -1.996 | Destabilizing | 0.984 | D | 0.723 | prob.delet. | N | 0.367334093 | None | None | I |
| I/T | 0.3404 | ambiguous | 0.3479 | ambiguous | -1.737 | Destabilizing | 0.896 | D | 0.566 | neutral | N | 0.379147179 | None | None | I |
| I/V | 0.077 | likely_benign | 0.0806 | benign | -0.976 | Destabilizing | 0.004 | N | 0.189 | neutral | N | 0.385560881 | None | None | I |
| I/W | 0.9498 | likely_pathogenic | 0.9502 | pathogenic | -1.073 | Destabilizing | 0.999 | D | 0.761 | deleterious | None | None | None | None | I |
| I/Y | 0.7725 | likely_pathogenic | 0.7817 | pathogenic | -0.832 | Destabilizing | 0.996 | D | 0.692 | prob.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.