Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14505 | 43738;43739;43740 | chr2:178632381;178632380;178632379 | chr2:179497108;179497107;179497106 |
| N2AB | 12864 | 38815;38816;38817 | chr2:178632381;178632380;178632379 | chr2:179497108;179497107;179497106 |
| N2A | 11937 | 36034;36035;36036 | chr2:178632381;178632380;178632379 | chr2:179497108;179497107;179497106 |
| N2B | 5440 | 16543;16544;16545 | chr2:178632381;178632380;178632379 | chr2:179497108;179497107;179497106 |
| Novex-1 | 5565 | 16918;16919;16920 | chr2:178632381;178632380;178632379 | chr2:179497108;179497107;179497106 |
| Novex-2 | 5632 | 17119;17120;17121 | chr2:178632381;178632380;178632379 | chr2:179497108;179497107;179497106 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | None | None | 1.0 | D | 0.449 | 0.608 | 0.552940642338 | gnomAD-4.0.0 | 6.90376E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.04395E-07 | 0 | 0 |
| D/H | rs1479425024  |
None | 1.0 | D | 0.721 | 0.552 | 0.668570387503 | gnomAD-2.1.1 | 4.36E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.64E-06 | 0 |
| D/H | rs1479425024 |
None | 1.0 | D | 0.721 | 0.552 | 0.668570387503 | gnomAD-4.0.0 | 1.62926E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.91404E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.7599 | likely_pathogenic | 0.6901 | pathogenic | -0.423 | Destabilizing | 1.0 | D | 0.775 | deleterious | D | 0.605220614 | None | None | N |
| D/C | 0.9832 | likely_pathogenic | 0.9762 | pathogenic | -0.113 | Destabilizing | 1.0 | D | 0.759 | deleterious | None | None | None | None | N |
| D/E | 0.7478 | likely_pathogenic | 0.6357 | pathogenic | -0.401 | Destabilizing | 1.0 | D | 0.449 | neutral | D | 0.677104363 | None | None | N |
| D/F | 0.984 | likely_pathogenic | 0.9772 | pathogenic | -0.144 | Destabilizing | 1.0 | D | 0.793 | deleterious | None | None | None | None | N |
| D/G | 0.6839 | likely_pathogenic | 0.6008 | pathogenic | -0.668 | Destabilizing | 1.0 | D | 0.765 | deleterious | D | 0.713351464 | None | None | N |
| D/H | 0.8987 | likely_pathogenic | 0.8502 | pathogenic | -0.019 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | D | 0.712302655 | None | None | N |
| D/I | 0.9646 | likely_pathogenic | 0.9532 | pathogenic | 0.192 | Stabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | N |
| D/K | 0.9588 | likely_pathogenic | 0.9404 | pathogenic | 0.205 | Stabilizing | 1.0 | D | 0.79 | deleterious | None | None | None | None | N |
| D/L | 0.9621 | likely_pathogenic | 0.9498 | pathogenic | 0.192 | Stabilizing | 1.0 | D | 0.81 | deleterious | None | None | None | None | N |
| D/M | 0.9858 | likely_pathogenic | 0.9794 | pathogenic | 0.329 | Stabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | N |
| D/N | 0.3509 | ambiguous | 0.2716 | benign | -0.27 | Destabilizing | 1.0 | D | 0.639 | neutral | D | 0.607185298 | None | None | N |
| D/P | 0.9313 | likely_pathogenic | 0.8947 | pathogenic | 0.01 | Stabilizing | 1.0 | D | 0.779 | deleterious | None | None | None | None | N |
| D/Q | 0.9624 | likely_pathogenic | 0.9407 | pathogenic | -0.199 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | None | None | None | None | N |
| D/R | 0.9697 | likely_pathogenic | 0.9607 | pathogenic | 0.437 | Stabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | N |
| D/S | 0.6248 | likely_pathogenic | 0.5176 | ambiguous | -0.376 | Destabilizing | 1.0 | D | 0.674 | neutral | None | None | None | None | N |
| D/T | 0.8861 | likely_pathogenic | 0.8389 | pathogenic | -0.174 | Destabilizing | 1.0 | D | 0.79 | deleterious | None | None | None | None | N |
| D/V | 0.8856 | likely_pathogenic | 0.8652 | pathogenic | 0.01 | Stabilizing | 1.0 | D | 0.811 | deleterious | D | 0.71241926 | None | None | N |
| D/W | 0.9961 | likely_pathogenic | 0.9946 | pathogenic | 0.068 | Stabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | N |
| D/Y | 0.8046 | likely_pathogenic | 0.7782 | pathogenic | 0.116 | Stabilizing | 1.0 | D | 0.785 | deleterious | D | 0.712378926 | 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.