Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25176 | 75751;75752;75753 | chr2:178570606;178570605;178570604 | chr2:179435333;179435332;179435331 |
| N2AB | 23535 | 70828;70829;70830 | chr2:178570606;178570605;178570604 | chr2:179435333;179435332;179435331 |
| N2A | 22608 | 68047;68048;68049 | chr2:178570606;178570605;178570604 | chr2:179435333;179435332;179435331 |
| N2B | 16111 | 48556;48557;48558 | chr2:178570606;178570605;178570604 | chr2:179435333;179435332;179435331 |
| Novex-1 | 16236 | 48931;48932;48933 | chr2:178570606;178570605;178570604 | chr2:179435333;179435332;179435331 |
| Novex-2 | 16303 | 49132;49133;49134 | chr2:178570606;178570605;178570604 | chr2:179435333;179435332;179435331 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/C | rs368339903  |
-0.22 | 1.0 | N | 0.733 | 0.394 | None | gnomAD-2.1.1 | 6.79E-05 | None | None | None | None | I | None | 8.27E-05 | 3.96511E-04 | None | 0 | 0 | None | 0 | None | 4E-05 | 1.56E-05 | 0 |
| R/C | rs368339903 |
-0.22 | 1.0 | N | 0.733 | 0.394 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 0 | 1.31199E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/C | rs368339903 |
-0.22 | 1.0 | N | 0.733 | 0.394 | None | gnomAD-4.0.0 | 2.04554E-05 | None | None | None | None | I | None | 4.00823E-05 | 2.83598E-04 | None | 0 | 0 | None | 0 | 0 | 6.78185E-06 | 2.19606E-05 | 4.80477E-05 |
| R/H | rs375693396 |
-1.14 | 1.0 | N | 0.687 | 0.349 | None | gnomAD-2.1.1 | 1.03669E-04 | None | None | None | None | I | None | 4.13E-05 | 2.26603E-04 | None | 0 | 0 | None | 0 | None | 0 | 1.33033E-04 | 4.21941E-04 |
| R/H | rs375693396 |
-1.14 | 1.0 | N | 0.687 | 0.349 | None | gnomAD-3.1.2 | 1.3153E-04 | None | None | None | None | I | None | 2.41E-05 | 3.27955E-04 | 0 | 0 | 0 | None | 0 | 0 | 1.9121E-04 | 0 | 4.78927E-04 |
| R/H | rs375693396 |
-1.14 | 1.0 | N | 0.687 | 0.349 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 1.4E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/H | rs375693396 |
-1.14 | 1.0 | N | 0.687 | 0.349 | None | gnomAD-4.0.0 | 1.20862E-04 | None | None | None | None | I | None | 1.33351E-05 | 2.33458E-04 | None | 0 | 0 | None | 0 | 1.65235E-04 | 1.45812E-04 | 0 | 1.12068E-04 |
| R/S | None | None | 1.0 | N | 0.594 | 0.421 | 0.289474373501 | gnomAD-4.0.0 | 6.84347E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.9958E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.8978 | likely_pathogenic | 0.9244 | pathogenic | -0.067 | Destabilizing | 0.999 | D | 0.512 | neutral | None | None | None | None | I |
| R/C | 0.5673 | likely_pathogenic | 0.6311 | pathogenic | -0.338 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | N | 0.517464072 | None | None | I |
| R/D | 0.9826 | likely_pathogenic | 0.9873 | pathogenic | -0.152 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | I |
| R/E | 0.9009 | likely_pathogenic | 0.9265 | pathogenic | -0.099 | Destabilizing | 0.999 | D | 0.533 | neutral | None | None | None | None | I |
| R/F | 0.9467 | likely_pathogenic | 0.9581 | pathogenic | -0.352 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | I |
| R/G | 0.8811 | likely_pathogenic | 0.9138 | pathogenic | -0.234 | Destabilizing | 1.0 | D | 0.561 | neutral | N | 0.490459047 | None | None | I |
| R/H | 0.503 | ambiguous | 0.5408 | ambiguous | -0.66 | Destabilizing | 1.0 | D | 0.687 | prob.neutral | N | 0.494244482 | None | None | I |
| R/I | 0.7951 | likely_pathogenic | 0.8242 | pathogenic | 0.333 | Stabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | I |
| R/K | 0.414 | ambiguous | 0.449 | ambiguous | -0.206 | Destabilizing | 0.998 | D | 0.439 | neutral | None | None | None | None | I |
| R/L | 0.7152 | likely_pathogenic | 0.7476 | pathogenic | 0.333 | Stabilizing | 1.0 | D | 0.561 | neutral | N | 0.45028361 | None | None | I |
| R/M | 0.8404 | likely_pathogenic | 0.8747 | pathogenic | -0.078 | Destabilizing | 1.0 | D | 0.69 | prob.neutral | None | None | None | None | I |
| R/N | 0.9655 | likely_pathogenic | 0.9742 | pathogenic | -0.073 | Destabilizing | 1.0 | D | 0.62 | neutral | None | None | None | None | I |
| R/P | 0.9224 | likely_pathogenic | 0.9344 | pathogenic | 0.219 | Stabilizing | 1.0 | D | 0.677 | prob.neutral | N | 0.451626736 | None | None | I |
| R/Q | 0.4517 | ambiguous | 0.5029 | ambiguous | -0.151 | Destabilizing | 1.0 | D | 0.613 | neutral | None | None | None | None | I |
| R/S | 0.9547 | likely_pathogenic | 0.9668 | pathogenic | -0.391 | Destabilizing | 1.0 | D | 0.594 | neutral | N | 0.470099839 | None | None | I |
| R/T | 0.876 | likely_pathogenic | 0.9082 | pathogenic | -0.214 | Destabilizing | 1.0 | D | 0.59 | neutral | None | None | None | None | I |
| R/V | 0.8553 | likely_pathogenic | 0.882 | pathogenic | 0.219 | Stabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | I |
| R/W | 0.577 | likely_pathogenic | 0.6352 | pathogenic | -0.443 | Destabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | I |
| R/Y | 0.8847 | likely_pathogenic | 0.909 | pathogenic | -0.033 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | 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.