Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 967 | 3124;3125;3126 | chr2:178783007;178783006;178783005 | chr2:179647734;179647733;179647732 |
| N2AB | 967 | 3124;3125;3126 | chr2:178783007;178783006;178783005 | chr2:179647734;179647733;179647732 |
| N2A | 967 | 3124;3125;3126 | chr2:178783007;178783006;178783005 | chr2:179647734;179647733;179647732 |
| N2B | 921 | 2986;2987;2988 | chr2:178783007;178783006;178783005 | chr2:179647734;179647733;179647732 |
| Novex-1 | 921 | 2986;2987;2988 | chr2:178783007;178783006;178783005 | chr2:179647734;179647733;179647732 |
| Novex-2 | 921 | 2986;2987;2988 | chr2:178783007;178783006;178783005 | chr2:179647734;179647733;179647732 |
| Novex-3 | 967 | 3124;3125;3126 | chr2:178783007;178783006;178783005 | chr2:179647734;179647733;179647732 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/P | rs768416555  |
None | 0.984 | D | 0.533 | 0.428 | 0.515375173082 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.83E-06 | 0 |
| S/P | rs768416555 |
None | 0.984 | D | 0.533 | 0.428 | 0.515375173082 | gnomAD-4.0.0 | 1.59055E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85659E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1085 | likely_benign | 0.1074 | benign | -0.414 | Destabilizing | 0.011 | N | 0.125 | neutral | N | 0.513929419 | None | None | I |
| S/C | 0.3301 | likely_benign | 0.3621 | ambiguous | -0.321 | Destabilizing | 0.999 | D | 0.537 | neutral | D | 0.607868356 | None | None | I |
| S/D | 0.731 | likely_pathogenic | 0.7226 | pathogenic | 0.239 | Stabilizing | 0.959 | D | 0.468 | neutral | None | None | None | None | I |
| S/E | 0.7174 | likely_pathogenic | 0.7118 | pathogenic | 0.19 | Stabilizing | 0.919 | D | 0.473 | neutral | None | None | None | None | I |
| S/F | 0.3947 | ambiguous | 0.4158 | ambiguous | -0.837 | Destabilizing | 0.995 | D | 0.604 | neutral | N | 0.512930592 | None | None | I |
| S/G | 0.2716 | likely_benign | 0.272 | benign | -0.595 | Destabilizing | 0.034 | N | 0.143 | neutral | None | None | None | None | I |
| S/H | 0.5892 | likely_pathogenic | 0.5737 | pathogenic | -1.049 | Destabilizing | 0.999 | D | 0.532 | neutral | None | None | None | None | I |
| S/I | 0.4054 | ambiguous | 0.408 | ambiguous | -0.063 | Destabilizing | 0.976 | D | 0.589 | neutral | None | None | None | None | I |
| S/K | 0.8483 | likely_pathogenic | 0.8299 | pathogenic | -0.476 | Destabilizing | 0.919 | D | 0.471 | neutral | None | None | None | None | I |
| S/L | 0.1773 | likely_benign | 0.1831 | benign | -0.063 | Destabilizing | 0.919 | D | 0.527 | neutral | None | None | None | None | I |
| S/M | 0.3632 | ambiguous | 0.3559 | ambiguous | 0.057 | Stabilizing | 0.999 | D | 0.531 | neutral | None | None | None | None | I |
| S/N | 0.4257 | ambiguous | 0.3779 | ambiguous | -0.309 | Destabilizing | 0.959 | D | 0.509 | neutral | None | None | None | None | I |
| S/P | 0.963 | likely_pathogenic | 0.9752 | pathogenic | -0.147 | Destabilizing | 0.984 | D | 0.533 | neutral | D | 0.684672034 | None | None | I |
| S/Q | 0.6756 | likely_pathogenic | 0.6543 | pathogenic | -0.46 | Destabilizing | 0.988 | D | 0.507 | neutral | None | None | None | None | I |
| S/R | 0.741 | likely_pathogenic | 0.7372 | pathogenic | -0.342 | Destabilizing | 0.988 | D | 0.537 | neutral | None | None | None | None | I |
| S/T | 0.1127 | likely_benign | 0.1044 | benign | -0.369 | Destabilizing | 0.896 | D | 0.491 | neutral | N | 0.454532338 | None | None | I |
| S/V | 0.3742 | ambiguous | 0.374 | ambiguous | -0.147 | Destabilizing | 0.851 | D | 0.512 | neutral | None | None | None | None | I |
| S/W | 0.62 | likely_pathogenic | 0.6802 | pathogenic | -0.855 | Destabilizing | 0.999 | D | 0.695 | prob.neutral | None | None | None | None | I |
| S/Y | 0.4025 | ambiguous | 0.4291 | ambiguous | -0.56 | Destabilizing | 0.995 | D | 0.597 | neutral | D | 0.545710084 | 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.