Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21203 | 63832;63833;63834 | chr2:178587702;178587701;178587700 | chr2:179452429;179452428;179452427 |
| N2AB | 19562 | 58909;58910;58911 | chr2:178587702;178587701;178587700 | chr2:179452429;179452428;179452427 |
| N2A | 18635 | 56128;56129;56130 | chr2:178587702;178587701;178587700 | chr2:179452429;179452428;179452427 |
| N2B | 12138 | 36637;36638;36639 | chr2:178587702;178587701;178587700 | chr2:179452429;179452428;179452427 |
| Novex-1 | 12263 | 37012;37013;37014 | chr2:178587702;178587701;178587700 | chr2:179452429;179452428;179452427 |
| Novex-2 | 12330 | 37213;37214;37215 | chr2:178587702;178587701;178587700 | chr2:179452429;179452428;179452427 |
| 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/D | rs544707116  |
-0.757 | 0.901 | N | 0.631 | 0.402 | 0.575814496085 | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | I | None | 1.294E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| A/D | rs544707116 |
-0.757 | 0.901 | N | 0.631 | 0.402 | 0.575814496085 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 7.25E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/D | rs544707116 |
-0.757 | 0.901 | N | 0.631 | 0.402 | 0.575814496085 | 1000 genomes | 5.99042E-04 | None | None | None | None | I | None | 2.3E-03 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| A/D | rs544707116 |
-0.757 | 0.901 | N | 0.631 | 0.402 | 0.575814496085 | gnomAD-4.0.0 | 1.31527E-05 | None | None | None | None | I | None | 4.81835E-05 | 0 | None | 0 | 0 | None | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.3827 | ambiguous | 0.3815 | ambiguous | -0.715 | Destabilizing | 0.996 | D | 0.497 | neutral | None | None | None | None | I |
| A/D | 0.3462 | ambiguous | 0.2933 | benign | -0.797 | Destabilizing | 0.901 | D | 0.631 | neutral | N | 0.487463529 | None | None | I |
| A/E | 0.2657 | likely_benign | 0.215 | benign | -0.954 | Destabilizing | 0.923 | D | 0.481 | neutral | None | None | None | None | I |
| A/F | 0.3248 | likely_benign | 0.2794 | benign | -0.997 | Destabilizing | 0.923 | D | 0.689 | prob.neutral | None | None | None | None | I |
| A/G | 0.1694 | likely_benign | 0.171 | benign | -0.447 | Destabilizing | 0.565 | D | 0.485 | neutral | N | 0.513218014 | None | None | I |
| A/H | 0.4191 | ambiguous | 0.3723 | ambiguous | -0.554 | Destabilizing | 0.996 | D | 0.699 | prob.neutral | None | None | None | None | I |
| A/I | 0.1795 | likely_benign | 0.1613 | benign | -0.424 | Destabilizing | 0.858 | D | 0.492 | neutral | None | None | None | None | I |
| A/K | 0.4092 | ambiguous | 0.3333 | benign | -0.87 | Destabilizing | 0.775 | D | 0.485 | neutral | None | None | None | None | I |
| A/L | 0.1365 | likely_benign | 0.1208 | benign | -0.424 | Destabilizing | 0.633 | D | 0.495 | neutral | None | None | None | None | I |
| A/M | 0.1796 | likely_benign | 0.1672 | benign | -0.414 | Destabilizing | 0.415 | N | 0.473 | neutral | None | None | None | None | I |
| A/N | 0.2354 | likely_benign | 0.2203 | benign | -0.457 | Destabilizing | 0.923 | D | 0.655 | neutral | None | None | None | None | I |
| A/P | 0.0975 | likely_benign | 0.0852 | benign | -0.379 | Destabilizing | 0.949 | D | 0.534 | neutral | N | 0.457425635 | None | None | I |
| A/Q | 0.2604 | likely_benign | 0.2339 | benign | -0.766 | Destabilizing | 0.923 | D | 0.527 | neutral | None | None | None | None | I |
| A/R | 0.396 | ambiguous | 0.3256 | benign | -0.351 | Destabilizing | 0.923 | D | 0.529 | neutral | None | None | None | None | I |
| A/S | 0.0913 | likely_benign | 0.0904 | benign | -0.603 | Destabilizing | 0.034 | N | 0.215 | neutral | D | 0.534462267 | None | None | I |
| A/T | 0.0833 | likely_benign | 0.076 | benign | -0.692 | Destabilizing | 0.008 | N | 0.232 | neutral | N | 0.444880412 | None | None | I |
| A/V | 0.1012 | likely_benign | 0.0922 | benign | -0.379 | Destabilizing | 0.565 | D | 0.475 | neutral | D | 0.524746705 | None | None | I |
| A/W | 0.6805 | likely_pathogenic | 0.6426 | pathogenic | -1.15 | Destabilizing | 0.996 | D | 0.751 | deleterious | None | None | None | None | I |
| A/Y | 0.4104 | ambiguous | 0.3825 | ambiguous | -0.819 | Destabilizing | 0.987 | D | 0.693 | prob.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.