Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1793 | 5602;5603;5604 | chr2:178776487;178776486;178776485 | chr2:179641214;179641213;179641212 |
| N2AB | 1793 | 5602;5603;5604 | chr2:178776487;178776486;178776485 | chr2:179641214;179641213;179641212 |
| N2A | 1793 | 5602;5603;5604 | chr2:178776487;178776486;178776485 | chr2:179641214;179641213;179641212 |
| N2B | 1747 | 5464;5465;5466 | chr2:178776487;178776486;178776485 | chr2:179641214;179641213;179641212 |
| Novex-1 | 1747 | 5464;5465;5466 | chr2:178776487;178776486;178776485 | chr2:179641214;179641213;179641212 |
| Novex-2 | 1747 | 5464;5465;5466 | chr2:178776487;178776486;178776485 | chr2:179641214;179641213;179641212 |
| Novex-3 | 1793 | 5602;5603;5604 | chr2:178776487;178776486;178776485 | chr2:179641214;179641213;179641212 |
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/F | None | None | 0.998 | N | 0.624 | 0.255 | 0.705458290464 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| I/T | rs746284395  |
-0.843 | 0.989 | N | 0.654 | 0.415 | 0.754311888153 | gnomAD-2.1.1 | 1.62E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 1.63399E-04 | None | 0 | None | 0 | 8.82E-06 | 0 |
| I/T | rs746284395 |
-0.843 | 0.989 | N | 0.654 | 0.415 | 0.754311888153 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/T | rs746284395 |
-0.843 | 0.989 | N | 0.654 | 0.415 | 0.754311888153 | gnomAD-4.0.0 | 1.05716E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 1.3366E-04 | None | 0 | 0 | 9.32205E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.7157 | likely_pathogenic | 0.6873 | pathogenic | -1.481 | Destabilizing | 0.992 | D | 0.547 | neutral | None | None | None | None | I |
| I/C | 0.9575 | likely_pathogenic | 0.9458 | pathogenic | -0.971 | Destabilizing | 1.0 | D | 0.665 | neutral | None | None | None | None | I |
| I/D | 0.9836 | likely_pathogenic | 0.9858 | pathogenic | -0.614 | Destabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | I |
| I/E | 0.9359 | likely_pathogenic | 0.9464 | pathogenic | -0.61 | Destabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | I |
| I/F | 0.4267 | ambiguous | 0.432 | ambiguous | -0.965 | Destabilizing | 0.998 | D | 0.624 | neutral | N | 0.510708286 | None | None | I |
| I/G | 0.9696 | likely_pathogenic | 0.9668 | pathogenic | -1.795 | Destabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | I |
| I/H | 0.893 | likely_pathogenic | 0.9051 | pathogenic | -0.934 | Destabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | I |
| I/K | 0.8961 | likely_pathogenic | 0.9141 | pathogenic | -0.907 | Destabilizing | 1.0 | D | 0.759 | deleterious | None | None | None | None | I |
| I/L | 0.2493 | likely_benign | 0.2296 | benign | -0.703 | Destabilizing | 0.889 | D | 0.367 | neutral | N | 0.493141674 | None | None | I |
| I/M | 0.2177 | likely_benign | 0.221 | benign | -0.607 | Destabilizing | 0.998 | D | 0.623 | neutral | N | 0.509529631 | None | None | I |
| I/N | 0.8516 | likely_pathogenic | 0.8629 | pathogenic | -0.743 | Destabilizing | 0.999 | D | 0.777 | deleterious | N | 0.498631922 | None | None | I |
| I/P | 0.9945 | likely_pathogenic | 0.9936 | pathogenic | -0.93 | Destabilizing | 1.0 | D | 0.78 | deleterious | None | None | None | None | I |
| I/Q | 0.8654 | likely_pathogenic | 0.8856 | pathogenic | -0.907 | Destabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | I |
| I/R | 0.8347 | likely_pathogenic | 0.8534 | pathogenic | -0.356 | Destabilizing | 1.0 | D | 0.778 | deleterious | None | None | None | None | I |
| I/S | 0.7773 | likely_pathogenic | 0.781 | pathogenic | -1.416 | Destabilizing | 0.998 | D | 0.71 | prob.delet. | N | 0.504584203 | None | None | I |
| I/T | 0.4442 | ambiguous | 0.4649 | ambiguous | -1.294 | Destabilizing | 0.989 | D | 0.654 | neutral | N | 0.478358811 | None | None | I |
| I/V | 0.1157 | likely_benign | 0.1033 | benign | -0.93 | Destabilizing | 0.333 | N | 0.184 | neutral | N | 0.465260049 | None | None | I |
| I/W | 0.9479 | likely_pathogenic | 0.9501 | pathogenic | -0.995 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | I |
| I/Y | 0.8599 | likely_pathogenic | 0.8717 | pathogenic | -0.772 | Destabilizing | 1.0 | D | 0.695 | 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.