Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21197 | 63814;63815;63816 | chr2:178587720;178587719;178587718 | chr2:179452447;179452446;179452445 |
| N2AB | 19556 | 58891;58892;58893 | chr2:178587720;178587719;178587718 | chr2:179452447;179452446;179452445 |
| N2A | 18629 | 56110;56111;56112 | chr2:178587720;178587719;178587718 | chr2:179452447;179452446;179452445 |
| N2B | 12132 | 36619;36620;36621 | chr2:178587720;178587719;178587718 | chr2:179452447;179452446;179452445 |
| Novex-1 | 12257 | 36994;36995;36996 | chr2:178587720;178587719;178587718 | chr2:179452447;179452446;179452445 |
| Novex-2 | 12324 | 37195;37196;37197 | chr2:178587720;178587719;178587718 | chr2:179452447;179452446;179452445 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs1473107263  |
None | 0.002 | N | 0.24 | 0.088 | 0.59202398213 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/T | rs1473107263 |
None | 0.002 | N | 0.24 | 0.088 | 0.59202398213 | gnomAD-4.0.0 | 7.69578E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.19771E-05 | 0 | 2.84787E-05 |
| I/V | rs72646855 |
-0.902 | 0.002 | N | 0.146 | 0.082 | None | gnomAD-2.1.1 | 6.05522E-04 | None | None | None | None | I | None | 1.65494E-04 | 1.70174E-04 | None | 0 | 0 | None | 7.52322E-04 | None | 3.60808E-04 | 9.88359E-04 | 1.41203E-04 |
| I/V | rs72646855 |
-0.902 | 0.002 | N | 0.146 | 0.082 | None | gnomAD-3.1.2 | 5.45866E-04 | None | None | None | None | I | None | 2.65457E-04 | 1.96773E-04 | 0 | 0 | 0 | None | 1.88253E-04 | 0 | 9.70874E-04 | 2.06954E-04 | 0 |
| I/V | rs72646855 |
-0.902 | 0.002 | N | 0.146 | 0.082 | None | gnomAD-4.0.0 | 7.41523E-04 | None | None | None | None | I | None | 2.00048E-04 | 2.0018E-04 | None | 0 | 4.48009E-05 | None | 3.90747E-04 | 0 | 8.83527E-04 | 6.81154E-04 | 6.08623E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.2727 | likely_benign | 0.2558 | benign | -0.839 | Destabilizing | 0.25 | N | 0.489 | neutral | None | None | None | None | I |
| I/C | 0.6823 | likely_pathogenic | 0.6669 | pathogenic | -0.587 | Destabilizing | 0.992 | D | 0.543 | neutral | None | None | None | None | I |
| I/D | 0.754 | likely_pathogenic | 0.7612 | pathogenic | -0.459 | Destabilizing | 0.85 | D | 0.629 | neutral | None | None | None | None | I |
| I/E | 0.6303 | likely_pathogenic | 0.6154 | pathogenic | -0.529 | Destabilizing | 0.85 | D | 0.628 | neutral | None | None | None | None | I |
| I/F | 0.2265 | likely_benign | 0.2206 | benign | -0.713 | Destabilizing | 0.92 | D | 0.507 | neutral | None | None | None | None | I |
| I/G | 0.6299 | likely_pathogenic | 0.6177 | pathogenic | -1.041 | Destabilizing | 0.617 | D | 0.619 | neutral | None | None | None | None | I |
| I/H | 0.5433 | ambiguous | 0.5161 | ambiguous | -0.28 | Destabilizing | 0.992 | D | 0.626 | neutral | None | None | None | None | I |
| I/K | 0.436 | ambiguous | 0.4117 | ambiguous | -0.552 | Destabilizing | 0.81 | D | 0.626 | neutral | N | 0.385061317 | None | None | I |
| I/L | 0.1309 | likely_benign | 0.1013 | benign | -0.407 | Destabilizing | 0.099 | N | 0.31 | neutral | N | 0.451326382 | None | None | I |
| I/M | 0.1076 | likely_benign | 0.1017 | benign | -0.453 | Destabilizing | 0.896 | D | 0.519 | neutral | N | 0.463794247 | None | None | I |
| I/N | 0.3123 | likely_benign | 0.308 | benign | -0.314 | Destabilizing | 0.85 | D | 0.627 | neutral | None | None | None | None | I |
| I/P | 0.7143 | likely_pathogenic | 0.6964 | pathogenic | -0.518 | Destabilizing | 0.92 | D | 0.625 | neutral | None | None | None | None | I |
| I/Q | 0.4791 | ambiguous | 0.4517 | ambiguous | -0.535 | Destabilizing | 0.92 | D | 0.649 | neutral | None | None | None | None | I |
| I/R | 0.356 | ambiguous | 0.3323 | benign | 0.034 | Stabilizing | 0.81 | D | 0.637 | neutral | N | 0.41805917 | None | None | I |
| I/S | 0.285 | likely_benign | 0.2867 | benign | -0.761 | Destabilizing | 0.447 | N | 0.597 | neutral | None | None | None | None | I |
| I/T | 0.1525 | likely_benign | 0.1595 | benign | -0.723 | Destabilizing | 0.002 | N | 0.24 | neutral | N | 0.353026257 | None | None | I |
| I/V | 0.0687 | likely_benign | 0.0705 | benign | -0.518 | Destabilizing | 0.002 | N | 0.146 | neutral | N | 0.40957576 | None | None | I |
| I/W | 0.8008 | likely_pathogenic | 0.7796 | pathogenic | -0.743 | Destabilizing | 0.992 | D | 0.644 | neutral | None | None | None | None | I |
| I/Y | 0.5522 | ambiguous | 0.5091 | ambiguous | -0.508 | Destabilizing | 0.972 | D | 0.574 | neutral | 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.