Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 7270 | 22033;22034;22035 | chr2:178723199;178723198;178723197 | chr2:179587926;179587925;179587924 |
| N2AB | 6953 | 21082;21083;21084 | chr2:178723199;178723198;178723197 | chr2:179587926;179587925;179587924 |
| N2A | 6026 | 18301;18302;18303 | chr2:178723199;178723198;178723197 | chr2:179587926;179587925;179587924 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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/K | None | None | 0.896 | D | 0.571 | 0.512 | 0.860919632765 | gnomAD-4.0.0 | 6.84338E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.9957E-07 | 0 | 0 |
| I/T | rs771364084  |
-1.931 | 0.549 | N | 0.456 | 0.38 | 0.6951284854 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.93E-06 | 0 |
| I/T | rs771364084 |
-1.931 | 0.549 | N | 0.456 | 0.38 | 0.6951284854 | 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 |
| I/T | rs771364084 |
-1.931 | 0.549 | N | 0.456 | 0.38 | 0.6951284854 | gnomAD-4.0.0 | 2.47909E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.39091E-06 | 0 | 0 |
| I/V | rs774554379 |
-1.07 | 0.002 | N | 0.149 | 0.071 | 0.36453787251 | gnomAD-4.0.0 | 1.59197E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.88374E-05 | 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 | 0.6221 | likely_pathogenic | 0.6692 | pathogenic | -1.987 | Destabilizing | 0.25 | N | 0.417 | neutral | None | None | None | None | N |
| I/C | 0.8161 | likely_pathogenic | 0.8151 | pathogenic | -1.348 | Destabilizing | 0.992 | D | 0.498 | neutral | None | None | None | None | N |
| I/D | 0.9394 | likely_pathogenic | 0.9467 | pathogenic | -1.424 | Destabilizing | 0.972 | D | 0.573 | neutral | None | None | None | None | N |
| I/E | 0.8709 | likely_pathogenic | 0.8877 | pathogenic | -1.318 | Destabilizing | 0.92 | D | 0.566 | neutral | None | None | None | None | N |
| I/F | 0.2109 | likely_benign | 0.2273 | benign | -1.244 | Destabilizing | 0.002 | N | 0.125 | neutral | None | None | None | None | N |
| I/G | 0.8803 | likely_pathogenic | 0.8981 | pathogenic | -2.408 | Highly Destabilizing | 0.92 | D | 0.557 | neutral | None | None | None | None | N |
| I/H | 0.8222 | likely_pathogenic | 0.8337 | pathogenic | -1.501 | Destabilizing | 0.992 | D | 0.566 | neutral | None | None | None | None | N |
| I/K | 0.7538 | likely_pathogenic | 0.7766 | pathogenic | -1.424 | Destabilizing | 0.896 | D | 0.571 | neutral | D | 0.535480233 | None | None | N |
| I/L | 0.0926 | likely_benign | 0.1031 | benign | -0.848 | Destabilizing | 0.001 | N | 0.09 | neutral | N | 0.440047809 | None | None | N |
| I/M | 0.1268 | likely_benign | 0.1413 | benign | -0.77 | Destabilizing | 0.81 | D | 0.506 | neutral | N | 0.513893258 | None | None | N |
| I/N | 0.6903 | likely_pathogenic | 0.707 | pathogenic | -1.472 | Destabilizing | 0.972 | D | 0.581 | neutral | None | None | None | None | N |
| I/P | 0.9205 | likely_pathogenic | 0.928 | pathogenic | -1.2 | Destabilizing | 0.972 | D | 0.578 | neutral | None | None | None | None | N |
| I/Q | 0.7825 | likely_pathogenic | 0.8037 | pathogenic | -1.487 | Destabilizing | 0.972 | D | 0.588 | neutral | None | None | None | None | N |
| I/R | 0.6687 | likely_pathogenic | 0.6928 | pathogenic | -0.957 | Destabilizing | 0.896 | D | 0.576 | neutral | D | 0.535480233 | None | None | N |
| I/S | 0.7143 | likely_pathogenic | 0.7409 | pathogenic | -2.173 | Highly Destabilizing | 0.617 | D | 0.488 | neutral | None | None | None | None | N |
| I/T | 0.5447 | ambiguous | 0.5907 | pathogenic | -1.921 | Destabilizing | 0.549 | D | 0.456 | neutral | N | 0.517461203 | None | None | N |
| I/V | 0.0833 | likely_benign | 0.0863 | benign | -1.2 | Destabilizing | 0.002 | N | 0.149 | neutral | N | 0.489615411 | None | None | N |
| I/W | 0.8806 | likely_pathogenic | 0.8899 | pathogenic | -1.369 | Destabilizing | 0.992 | D | 0.569 | neutral | None | None | None | None | N |
| I/Y | 0.6823 | likely_pathogenic | 0.6872 | pathogenic | -1.13 | Destabilizing | 0.447 | N | 0.483 | 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.