Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22564 | 67915;67916;67917 | chr2:178579340;178579339;178579338 | chr2:179444067;179444066;179444065 |
| N2AB | 20923 | 62992;62993;62994 | chr2:178579340;178579339;178579338 | chr2:179444067;179444066;179444065 |
| N2A | 19996 | 60211;60212;60213 | chr2:178579340;178579339;178579338 | chr2:179444067;179444066;179444065 |
| N2B | 13499 | 40720;40721;40722 | chr2:178579340;178579339;178579338 | chr2:179444067;179444066;179444065 |
| Novex-1 | 13624 | 41095;41096;41097 | chr2:178579340;178579339;178579338 | chr2:179444067;179444066;179444065 |
| Novex-2 | 13691 | 41296;41297;41298 | chr2:178579340;178579339;178579338 | chr2:179444067;179444066;179444065 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/D | None | None | 0.999 | N | 0.407 | 0.315 | 0.240491677333 | gnomAD-4.0.0 | 1.6116E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.89024E-06 | 0 | 0 |
| E/G | rs559039977  |
-0.902 | 1.0 | N | 0.679 | 0.511 | 0.507867570733 | gnomAD-2.1.1 | 4.1E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.33E-05 | None | 0 | 0 | 0 |
| E/G | rs559039977 |
-0.902 | 1.0 | N | 0.679 | 0.511 | 0.507867570733 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07039E-04 | 0 |
| E/G | rs559039977 |
-0.902 | 1.0 | N | 0.679 | 0.511 | 0.507867570733 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| E/G | rs559039977 |
-0.902 | 1.0 | N | 0.679 | 0.511 | 0.507867570733 | gnomAD-4.0.0 | 6.56987E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.07211E-04 | 0 |
| E/K | rs2047149895 |
None | 0.999 | N | 0.537 | 0.367 | 0.362758974969 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 9.42E-05 | 0 | 0 | 0 | 0 |
| E/K | rs2047149895 |
None | 0.999 | N | 0.537 | 0.367 | 0.362758974969 | gnomAD-4.0.0 | 6.57748E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 9.42329E-05 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | 0.3119 | likely_benign | 0.2787 | benign | -0.648 | Destabilizing | 0.999 | D | 0.572 | neutral | N | 0.467734976 | None | None | I |
| E/C | 0.965 | likely_pathogenic | 0.9571 | pathogenic | -0.216 | Destabilizing | 1.0 | D | 0.762 | deleterious | None | None | None | None | I |
| E/D | 0.5994 | likely_pathogenic | 0.5871 | pathogenic | -0.897 | Destabilizing | 0.999 | D | 0.407 | neutral | N | 0.476232813 | None | None | I |
| E/F | 0.9693 | likely_pathogenic | 0.9583 | pathogenic | -0.572 | Destabilizing | 1.0 | D | 0.748 | deleterious | None | None | None | None | I |
| E/G | 0.4945 | ambiguous | 0.4397 | ambiguous | -0.921 | Destabilizing | 1.0 | D | 0.679 | prob.neutral | N | 0.499198914 | None | None | I |
| E/H | 0.9085 | likely_pathogenic | 0.8893 | pathogenic | -0.808 | Destabilizing | 1.0 | D | 0.645 | neutral | None | None | None | None | I |
| E/I | 0.642 | likely_pathogenic | 0.6076 | pathogenic | 0.063 | Stabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | I |
| E/K | 0.5204 | ambiguous | 0.4788 | ambiguous | -0.308 | Destabilizing | 0.999 | D | 0.537 | neutral | N | 0.458177784 | None | None | I |
| E/L | 0.7757 | likely_pathogenic | 0.7325 | pathogenic | 0.063 | Stabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | I |
| E/M | 0.7523 | likely_pathogenic | 0.7133 | pathogenic | 0.44 | Stabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | I |
| E/N | 0.7643 | likely_pathogenic | 0.7204 | pathogenic | -0.57 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | I |
| E/P | 0.9602 | likely_pathogenic | 0.946 | pathogenic | -0.152 | Destabilizing | 1.0 | D | 0.666 | neutral | None | None | None | None | I |
| E/Q | 0.2762 | likely_benign | 0.2429 | benign | -0.521 | Destabilizing | 1.0 | D | 0.628 | neutral | N | 0.462394519 | None | None | I |
| E/R | 0.7068 | likely_pathogenic | 0.6656 | pathogenic | -0.171 | Destabilizing | 1.0 | D | 0.682 | prob.neutral | None | None | None | None | I |
| E/S | 0.6071 | likely_pathogenic | 0.5491 | ambiguous | -0.796 | Destabilizing | 0.999 | D | 0.619 | neutral | None | None | None | None | I |
| E/T | 0.6322 | likely_pathogenic | 0.5781 | pathogenic | -0.584 | Destabilizing | 1.0 | D | 0.687 | prob.neutral | None | None | None | None | I |
| E/V | 0.4201 | ambiguous | 0.3895 | ambiguous | -0.152 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | N | 0.46496403 | None | None | I |
| E/W | 0.99 | likely_pathogenic | 0.9867 | pathogenic | -0.455 | Destabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | I |
| E/Y | 0.9364 | likely_pathogenic | 0.92 | pathogenic | -0.356 | Destabilizing | 1.0 | D | 0.74 | deleterious | 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.