Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27390 | 82393;82394;82395 | chr2:178563964;178563963;178563962 | chr2:179428691;179428690;179428689 |
| N2AB | 25749 | 77470;77471;77472 | chr2:178563964;178563963;178563962 | chr2:179428691;179428690;179428689 |
| N2A | 24822 | 74689;74690;74691 | chr2:178563964;178563963;178563962 | chr2:179428691;179428690;179428689 |
| N2B | 18325 | 55198;55199;55200 | chr2:178563964;178563963;178563962 | chr2:179428691;179428690;179428689 |
| Novex-1 | 18450 | 55573;55574;55575 | chr2:178563964;178563963;178563962 | chr2:179428691;179428690;179428689 |
| Novex-2 | 18517 | 55774;55775;55776 | chr2:178563964;178563963;178563962 | chr2:179428691;179428690;179428689 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/T | rs1249245369  |
-1.465 | 0.028 | N | 0.433 | 0.215 | 0.390687800842 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.58E-05 | None | 0 | None | 0 | 0 | 0 |
| A/T | rs1249245369 |
-1.465 | 0.028 | N | 0.433 | 0.215 | 0.390687800842 | gnomAD-4.0.0 | 1.36848E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.52067E-05 | None | 0 | 0 | 8.99505E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.3148 | likely_benign | 0.3436 | ambiguous | -0.915 | Destabilizing | 0.996 | D | 0.616 | neutral | None | None | None | None | N |
| A/D | 0.3344 | likely_benign | 0.38 | ambiguous | -2.082 | Highly Destabilizing | 0.742 | D | 0.669 | neutral | None | None | None | None | N |
| A/E | 0.2678 | likely_benign | 0.2963 | benign | -1.965 | Destabilizing | 0.684 | D | 0.623 | neutral | N | 0.45375532 | None | None | N |
| A/F | 0.2247 | likely_benign | 0.2605 | benign | -0.846 | Destabilizing | 0.91 | D | 0.682 | prob.neutral | None | None | None | None | N |
| A/G | 0.1316 | likely_benign | 0.1446 | benign | -1.424 | Destabilizing | 0.521 | D | 0.509 | neutral | N | 0.512862338 | None | None | N |
| A/H | 0.3584 | ambiguous | 0.3981 | ambiguous | -1.943 | Destabilizing | 0.009 | N | 0.554 | neutral | None | None | None | None | N |
| A/I | 0.186 | likely_benign | 0.2079 | benign | 0.036 | Stabilizing | 0.59 | D | 0.653 | neutral | None | None | None | None | N |
| A/K | 0.4732 | ambiguous | 0.5268 | ambiguous | -1.374 | Destabilizing | 0.742 | D | 0.647 | neutral | None | None | None | None | N |
| A/L | 0.1315 | likely_benign | 0.1421 | benign | 0.036 | Stabilizing | 0.59 | D | 0.582 | neutral | None | None | None | None | N |
| A/M | 0.1698 | likely_benign | 0.1876 | benign | 0.028 | Stabilizing | 0.953 | D | 0.626 | neutral | None | None | None | None | N |
| A/N | 0.2232 | likely_benign | 0.2484 | benign | -1.389 | Destabilizing | 0.742 | D | 0.669 | neutral | None | None | None | None | N |
| A/P | 0.862 | likely_pathogenic | 0.8808 | pathogenic | -0.269 | Destabilizing | 0.939 | D | 0.678 | prob.neutral | N | 0.491385597 | None | None | N |
| A/Q | 0.2937 | likely_benign | 0.3192 | benign | -1.328 | Destabilizing | 0.953 | D | 0.659 | neutral | None | None | None | None | N |
| A/R | 0.4118 | ambiguous | 0.4605 | ambiguous | -1.293 | Destabilizing | 0.91 | D | 0.682 | prob.neutral | None | None | None | None | N |
| A/S | 0.0769 | likely_benign | 0.0798 | benign | -1.741 | Destabilizing | 0.028 | N | 0.415 | neutral | N | 0.366440192 | None | None | N |
| A/T | 0.0771 | likely_benign | 0.0806 | benign | -1.514 | Destabilizing | 0.028 | N | 0.433 | neutral | N | 0.435900278 | None | None | N |
| A/V | 0.1126 | likely_benign | 0.1224 | benign | -0.269 | Destabilizing | 0.007 | N | 0.398 | neutral | N | 0.491025629 | None | None | N |
| A/W | 0.591 | likely_pathogenic | 0.6644 | pathogenic | -1.558 | Destabilizing | 0.996 | D | 0.714 | prob.delet. | None | None | None | None | N |
| A/Y | 0.3109 | likely_benign | 0.3589 | ambiguous | -1.005 | Destabilizing | 0.91 | D | 0.671 | neutral | None | None | 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.