Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2251 | 6976;6977;6978 | chr2:178774960;178774959;178774958 | chr2:179639687;179639686;179639685 |
| N2AB | 2251 | 6976;6977;6978 | chr2:178774960;178774959;178774958 | chr2:179639687;179639686;179639685 |
| N2A | 2251 | 6976;6977;6978 | chr2:178774960;178774959;178774958 | chr2:179639687;179639686;179639685 |
| N2B | 2205 | 6838;6839;6840 | chr2:178774960;178774959;178774958 | chr2:179639687;179639686;179639685 |
| Novex-1 | 2205 | 6838;6839;6840 | chr2:178774960;178774959;178774958 | chr2:179639687;179639686;179639685 |
| Novex-2 | 2205 | 6838;6839;6840 | chr2:178774960;178774959;178774958 | chr2:179639687;179639686;179639685 |
| Novex-3 | 2251 | 6976;6977;6978 | chr2:178774960;178774959;178774958 | chr2:179639687;179639686;179639685 |
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 | 0.767 | N | 0.482 | 0.092 | 0.0806252709748 | gnomAD-4.0.0 | 1.36839E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79877E-06 | 0 | 0 |
| D/H | rs942953757  |
0.325 | 1.0 | N | 0.711 | 0.407 | 0.130388298395 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.82E-06 | 0 |
| D/H | rs942953757 |
0.325 | 1.0 | N | 0.711 | 0.407 | 0.130388298395 | gnomAD-4.0.0 | 2.73742E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.598E-06 | 0 | 0 |
| D/N | rs942953757 |
0.415 | 0.999 | N | 0.693 | 0.279 | 0.141422826196 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/N | rs942953757 |
0.415 | 0.999 | N | 0.693 | 0.279 | 0.141422826196 | gnomAD-4.0.0 | 6.57263E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47011E-05 | 0 | 0 |
| D/V | None | None | 0.999 | N | 0.719 | 0.483 | 0.357929162469 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 | 0.1982 | likely_benign | 0.218 | benign | -0.281 | Destabilizing | 0.999 | D | 0.647 | neutral | N | 0.344257283 | None | None | N |
| D/C | 0.723 | likely_pathogenic | 0.7334 | pathogenic | 0.016 | Stabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | N |
| D/E | 0.19 | likely_benign | 0.2026 | benign | -0.339 | Destabilizing | 0.767 | D | 0.482 | neutral | N | 0.327490044 | None | None | N |
| D/F | 0.6457 | likely_pathogenic | 0.6825 | pathogenic | -0.209 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | N |
| D/G | 0.1987 | likely_benign | 0.2173 | benign | -0.48 | Destabilizing | 0.998 | D | 0.659 | neutral | N | 0.34527008 | None | None | N |
| D/H | 0.3297 | likely_benign | 0.3568 | ambiguous | -0.028 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | N | 0.352285478 | None | None | N |
| D/I | 0.4805 | ambiguous | 0.5209 | ambiguous | 0.197 | Stabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | N |
| D/K | 0.4383 | ambiguous | 0.4835 | ambiguous | 0.33 | Stabilizing | 0.999 | D | 0.675 | neutral | None | None | None | None | N |
| D/L | 0.4597 | ambiguous | 0.4896 | ambiguous | 0.197 | Stabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | N |
| D/M | 0.6067 | likely_pathogenic | 0.6343 | pathogenic | 0.306 | Stabilizing | 1.0 | D | 0.738 | prob.delet. | None | None | None | None | N |
| D/N | 0.0884 | likely_benign | 0.0905 | benign | -0.012 | Destabilizing | 0.999 | D | 0.693 | prob.neutral | N | 0.336946511 | None | None | N |
| D/P | 0.8395 | likely_pathogenic | 0.8625 | pathogenic | 0.06 | Stabilizing | 1.0 | D | 0.705 | prob.neutral | None | None | None | None | N |
| D/Q | 0.3834 | ambiguous | 0.4089 | ambiguous | 0.025 | Stabilizing | 0.999 | D | 0.736 | prob.delet. | None | None | None | None | N |
| D/R | 0.4806 | ambiguous | 0.531 | ambiguous | 0.503 | Stabilizing | 0.999 | D | 0.722 | prob.delet. | None | None | None | None | N |
| D/S | 0.1491 | likely_benign | 0.1575 | benign | -0.106 | Destabilizing | 0.997 | D | 0.672 | neutral | None | None | None | None | N |
| D/T | 0.2992 | likely_benign | 0.3209 | benign | 0.051 | Stabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | N |
| D/V | 0.2738 | likely_benign | 0.3022 | benign | 0.06 | Stabilizing | 0.999 | D | 0.719 | prob.delet. | N | 0.329464401 | None | None | N |
| D/W | 0.8875 | likely_pathogenic | 0.9058 | pathogenic | -0.074 | Destabilizing | 1.0 | D | 0.756 | deleterious | None | None | None | None | N |
| D/Y | 0.2565 | likely_benign | 0.2741 | benign | 0.032 | Stabilizing | 1.0 | D | 0.723 | prob.delet. | N | 0.367199217 | 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.