Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33666 | 101221;101222;101223 | chr2:178535619;178535618;178535617 | chr2:179400346;179400345;179400344 |
| N2AB | 32025 | 96298;96299;96300 | chr2:178535619;178535618;178535617 | chr2:179400346;179400345;179400344 |
| N2A | 31098 | 93517;93518;93519 | chr2:178535619;178535618;178535617 | chr2:179400346;179400345;179400344 |
| N2B | 24601 | 74026;74027;74028 | chr2:178535619;178535618;178535617 | chr2:179400346;179400345;179400344 |
| Novex-1 | 24726 | 74401;74402;74403 | chr2:178535619;178535618;178535617 | chr2:179400346;179400345;179400344 |
| Novex-2 | 24793 | 74602;74603;74604 | chr2:178535619;178535618;178535617 | chr2:179400346;179400345;179400344 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/L | rs752263533  |
-1.024 | 0.983 | N | 0.585 | 0.43 | 0.502691689211 | gnomAD-2.1.1 | 2.82E-05 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 5.34E-05 | 0 |
| F/L | rs752263533 |
-1.024 | 0.983 | N | 0.585 | 0.43 | 0.502691689211 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| F/L | rs752263533 |
-1.024 | 0.983 | N | 0.585 | 0.43 | 0.502691689211 | gnomAD-4.0.0 | 3.90422E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.32285E-05 | 1.09794E-04 | 3.20215E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.8988 | likely_pathogenic | 0.8281 | pathogenic | -1.44 | Destabilizing | 0.997 | D | 0.639 | neutral | None | None | None | None | N |
| F/C | 0.7349 | likely_pathogenic | 0.6156 | pathogenic | -0.479 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | N | 0.494866515 | None | None | N |
| F/D | 0.9546 | likely_pathogenic | 0.9205 | pathogenic | 0.446 | Stabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | N |
| F/E | 0.9623 | likely_pathogenic | 0.925 | pathogenic | 0.464 | Stabilizing | 0.999 | D | 0.742 | deleterious | None | None | None | None | N |
| F/G | 0.9612 | likely_pathogenic | 0.9284 | pathogenic | -1.693 | Destabilizing | 1.0 | D | 0.714 | prob.delet. | None | None | None | None | N |
| F/H | 0.8133 | likely_pathogenic | 0.7492 | pathogenic | -0.07 | Destabilizing | 0.995 | D | 0.723 | prob.delet. | None | None | None | None | N |
| F/I | 0.5823 | likely_pathogenic | 0.4537 | ambiguous | -0.741 | Destabilizing | 0.998 | D | 0.638 | neutral | N | 0.43933852 | None | None | N |
| F/K | 0.961 | likely_pathogenic | 0.9249 | pathogenic | -0.394 | Destabilizing | 0.998 | D | 0.745 | deleterious | None | None | None | None | N |
| F/L | 0.956 | likely_pathogenic | 0.9253 | pathogenic | -0.741 | Destabilizing | 0.983 | D | 0.585 | neutral | N | 0.439858595 | None | None | N |
| F/M | 0.8076 | likely_pathogenic | 0.7184 | pathogenic | -0.535 | Destabilizing | 0.998 | D | 0.652 | neutral | None | None | None | None | N |
| F/N | 0.8272 | likely_pathogenic | 0.7387 | pathogenic | -0.314 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | N |
| F/P | 0.9892 | likely_pathogenic | 0.9823 | pathogenic | -0.958 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | N |
| F/Q | 0.9351 | likely_pathogenic | 0.8845 | pathogenic | -0.389 | Destabilizing | 0.999 | D | 0.732 | prob.delet. | None | None | None | None | N |
| F/R | 0.9159 | likely_pathogenic | 0.8595 | pathogenic | 0.167 | Stabilizing | 0.998 | D | 0.735 | prob.delet. | None | None | None | None | N |
| F/S | 0.8053 | likely_pathogenic | 0.714 | pathogenic | -1.094 | Destabilizing | 0.999 | D | 0.729 | prob.delet. | N | 0.433969985 | None | None | N |
| F/T | 0.8458 | likely_pathogenic | 0.7543 | pathogenic | -0.985 | Destabilizing | 0.999 | D | 0.739 | prob.delet. | None | None | None | None | N |
| F/V | 0.5726 | likely_pathogenic | 0.4565 | ambiguous | -0.958 | Destabilizing | 0.976 | D | 0.657 | neutral | N | 0.425774576 | None | None | N |
| F/W | 0.7502 | likely_pathogenic | 0.6808 | pathogenic | -0.256 | Destabilizing | 1.0 | D | 0.651 | neutral | None | None | None | None | N |
| F/Y | 0.1956 | likely_benign | 0.1665 | benign | -0.349 | Destabilizing | 0.124 | N | 0.273 | neutral | N | 0.465333042 | 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.