Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27028 | 81307;81308;81309 | chr2:178565050;178565049;178565048 | chr2:179429777;179429776;179429775 |
| N2AB | 25387 | 76384;76385;76386 | chr2:178565050;178565049;178565048 | chr2:179429777;179429776;179429775 |
| N2A | 24460 | 73603;73604;73605 | chr2:178565050;178565049;178565048 | chr2:179429777;179429776;179429775 |
| N2B | 17963 | 54112;54113;54114 | chr2:178565050;178565049;178565048 | chr2:179429777;179429776;179429775 |
| Novex-1 | 18088 | 54487;54488;54489 | chr2:178565050;178565049;178565048 | chr2:179429777;179429776;179429775 |
| Novex-2 | 18155 | 54688;54689;54690 | chr2:178565050;178565049;178565048 | chr2:179429777;179429776;179429775 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/P | rs1356707489  |
-0.048 | 0.994 | N | 0.709 | 0.403 | 0.378674557249 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| A/P | rs1356707489 |
-0.048 | 0.994 | N | 0.709 | 0.403 | 0.378674557249 | gnomAD-4.0.0 | 6.36639E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.14361E-05 | 0 | 0 |
| A/V | None | None | 0.958 | N | 0.627 | 0.33 | 0.47737504017 | gnomAD-4.0.0 | 1.59164E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85897E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.8154 | likely_pathogenic | 0.8527 | pathogenic | -0.815 | Destabilizing | 1.0 | D | 0.656 | neutral | None | None | None | None | N |
| A/D | 0.9889 | likely_pathogenic | 0.9919 | pathogenic | -0.436 | Destabilizing | 0.991 | D | 0.665 | neutral | None | None | None | None | N |
| A/E | 0.9724 | likely_pathogenic | 0.98 | pathogenic | -0.537 | Destabilizing | 0.988 | D | 0.681 | prob.neutral | N | 0.515574569 | None | None | N |
| A/F | 0.8758 | likely_pathogenic | 0.8926 | pathogenic | -0.861 | Destabilizing | 0.995 | D | 0.682 | prob.neutral | None | None | None | None | N |
| A/G | 0.61 | likely_pathogenic | 0.6446 | pathogenic | -0.66 | Destabilizing | 0.919 | D | 0.496 | neutral | N | 0.508995314 | None | None | N |
| A/H | 0.9695 | likely_pathogenic | 0.9766 | pathogenic | -0.654 | Destabilizing | 1.0 | D | 0.637 | neutral | None | None | None | None | N |
| A/I | 0.6996 | likely_pathogenic | 0.7344 | pathogenic | -0.33 | Destabilizing | 0.995 | D | 0.708 | prob.delet. | None | None | None | None | N |
| A/K | 0.9837 | likely_pathogenic | 0.988 | pathogenic | -0.846 | Destabilizing | 0.991 | D | 0.685 | prob.neutral | None | None | None | None | N |
| A/L | 0.5381 | ambiguous | 0.5843 | pathogenic | -0.33 | Destabilizing | 0.968 | D | 0.678 | prob.neutral | None | None | None | None | N |
| A/M | 0.6747 | likely_pathogenic | 0.7104 | pathogenic | -0.443 | Destabilizing | 1.0 | D | 0.673 | neutral | None | None | None | None | N |
| A/N | 0.9063 | likely_pathogenic | 0.9268 | pathogenic | -0.548 | Destabilizing | 0.991 | D | 0.669 | neutral | None | None | None | None | N |
| A/P | 0.7921 | likely_pathogenic | 0.8292 | pathogenic | -0.356 | Destabilizing | 0.994 | D | 0.709 | prob.delet. | N | 0.497719527 | None | None | N |
| A/Q | 0.9038 | likely_pathogenic | 0.9225 | pathogenic | -0.75 | Destabilizing | 0.991 | D | 0.709 | prob.delet. | None | None | None | None | N |
| A/R | 0.9555 | likely_pathogenic | 0.9671 | pathogenic | -0.433 | Destabilizing | 0.991 | D | 0.703 | prob.neutral | None | None | None | None | N |
| A/S | 0.3073 | likely_benign | 0.344 | ambiguous | -0.834 | Destabilizing | 0.414 | N | 0.293 | neutral | N | 0.483038077 | None | None | N |
| A/T | 0.5258 | ambiguous | 0.5732 | pathogenic | -0.84 | Destabilizing | 0.919 | D | 0.594 | neutral | N | 0.480747133 | None | None | N |
| A/V | 0.5195 | ambiguous | 0.5789 | pathogenic | -0.356 | Destabilizing | 0.958 | D | 0.627 | neutral | N | 0.49914368 | None | None | N |
| A/W | 0.9824 | likely_pathogenic | 0.9872 | pathogenic | -1.062 | Destabilizing | 1.0 | D | 0.694 | prob.neutral | None | None | None | None | N |
| A/Y | 0.9457 | likely_pathogenic | 0.957 | pathogenic | -0.696 | Destabilizing | 1.0 | D | 0.675 | neutral | 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.