Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25430 | 76513;76514;76515 | chr2:178569844;178569843;178569842 | chr2:179434571;179434570;179434569 |
| N2AB | 23789 | 71590;71591;71592 | chr2:178569844;178569843;178569842 | chr2:179434571;179434570;179434569 |
| N2A | 22862 | 68809;68810;68811 | chr2:178569844;178569843;178569842 | chr2:179434571;179434570;179434569 |
| N2B | 16365 | 49318;49319;49320 | chr2:178569844;178569843;178569842 | chr2:179434571;179434570;179434569 |
| Novex-1 | 16490 | 49693;49694;49695 | chr2:178569844;178569843;178569842 | chr2:179434571;179434570;179434569 |
| Novex-2 | 16557 | 49894;49895;49896 | chr2:178569844;178569843;178569842 | chr2:179434571;179434570;179434569 |
| 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/M | None | None | 0.864 | N | 0.568 | 0.186 | 0.326345978581 | gnomAD-4.0.0 | 1.59184E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85917E-06 | 0 | 0 |
| I/T | rs2154168088  |
None | 0.645 | N | 0.545 | 0.185 | 0.552781577438 | gnomAD-4.0.0 | 4.8013E-06 | None | None | None | None | I | None | 1.26695E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 2.625E-06 | 0 | 0 |
| I/V | rs756888687 |
-0.032 | 0.002 | N | 0.235 | 0.053 | 0.373173300195 | gnomAD-2.1.1 | 1.07E-05 | None | None | None | None | I | None | 8.27E-05 | 2.83E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/V | rs756888687 |
-0.032 | 0.002 | N | 0.235 | 0.053 | 0.373173300195 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs756888687 |
-0.032 | 0.002 | N | 0.235 | 0.053 | 0.373173300195 | gnomAD-4.0.0 | 5.12638E-06 | None | None | None | None | I | None | 5.07631E-05 | 1.69555E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.4965 | ambiguous | 0.4356 | ambiguous | -0.592 | Destabilizing | 0.547 | D | 0.545 | neutral | None | None | None | None | I |
| I/C | 0.8275 | likely_pathogenic | 0.7929 | pathogenic | -0.615 | Destabilizing | 0.985 | D | 0.575 | neutral | None | None | None | None | I |
| I/D | 0.9093 | likely_pathogenic | 0.8766 | pathogenic | -0.443 | Destabilizing | 0.945 | D | 0.667 | neutral | None | None | None | None | I |
| I/E | 0.8727 | likely_pathogenic | 0.8409 | pathogenic | -0.533 | Destabilizing | 0.945 | D | 0.671 | neutral | None | None | None | None | I |
| I/F | 0.3364 | likely_benign | 0.2905 | benign | -0.601 | Destabilizing | 0.894 | D | 0.583 | neutral | None | None | None | None | I |
| I/G | 0.8314 | likely_pathogenic | 0.7865 | pathogenic | -0.747 | Destabilizing | 0.945 | D | 0.684 | prob.neutral | None | None | None | None | I |
| I/H | 0.783 | likely_pathogenic | 0.7428 | pathogenic | -0.019 | Destabilizing | 0.995 | D | 0.665 | neutral | None | None | None | None | I |
| I/K | 0.7507 | likely_pathogenic | 0.7326 | pathogenic | -0.424 | Destabilizing | 0.928 | D | 0.671 | neutral | N | 0.469799421 | None | None | I |
| I/L | 0.1376 | likely_benign | 0.1176 | benign | -0.301 | Destabilizing | 0.141 | N | 0.317 | neutral | N | 0.446655989 | None | None | I |
| I/M | 0.1696 | likely_benign | 0.1544 | benign | -0.465 | Destabilizing | 0.864 | D | 0.568 | neutral | N | 0.507224445 | None | None | I |
| I/N | 0.5725 | likely_pathogenic | 0.526 | ambiguous | -0.217 | Destabilizing | 0.981 | D | 0.667 | neutral | None | None | None | None | I |
| I/P | 0.8301 | likely_pathogenic | 0.8119 | pathogenic | -0.366 | Destabilizing | 0.981 | D | 0.674 | neutral | None | None | None | None | I |
| I/Q | 0.757 | likely_pathogenic | 0.721 | pathogenic | -0.449 | Destabilizing | 0.981 | D | 0.657 | neutral | None | None | None | None | I |
| I/R | 0.6248 | likely_pathogenic | 0.5943 | pathogenic | 0.152 | Stabilizing | 0.928 | D | 0.663 | neutral | N | 0.505490862 | None | None | I |
| I/S | 0.5361 | ambiguous | 0.4906 | ambiguous | -0.601 | Destabilizing | 0.894 | D | 0.617 | neutral | None | None | None | None | I |
| I/T | 0.5248 | ambiguous | 0.4818 | ambiguous | -0.588 | Destabilizing | 0.645 | D | 0.545 | neutral | N | 0.47568803 | None | None | I |
| I/V | 0.0855 | likely_benign | 0.078 | benign | -0.366 | Destabilizing | 0.002 | N | 0.235 | neutral | N | 0.467377978 | None | None | I |
| I/W | 0.9125 | likely_pathogenic | 0.897 | pathogenic | -0.62 | Destabilizing | 0.995 | D | 0.725 | prob.delet. | None | None | None | None | I |
| I/Y | 0.7471 | likely_pathogenic | 0.7042 | pathogenic | -0.385 | Destabilizing | 0.945 | D | 0.565 | 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.