Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35618 | 107077;107078;107079 | chr2:178528899;178528898;178528897 | chr2:179393626;179393625;179393624 |
| N2AB | 33977 | 102154;102155;102156 | chr2:178528899;178528898;178528897 | chr2:179393626;179393625;179393624 |
| N2A | 33050 | 99373;99374;99375 | chr2:178528899;178528898;178528897 | chr2:179393626;179393625;179393624 |
| N2B | 26553 | 79882;79883;79884 | chr2:178528899;178528898;178528897 | chr2:179393626;179393625;179393624 |
| Novex-1 | 26678 | 80257;80258;80259 | chr2:178528899;178528898;178528897 | chr2:179393626;179393625;179393624 |
| Novex-2 | 26745 | 80458;80459;80460 | chr2:178528899;178528898;178528897 | chr2:179393626;179393625;179393624 |
| 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 | rs1687755639  |
None | 0.81 | N | 0.606 | 0.22 | 0.512366387742 | gnomAD-4.0.0 | 3.18176E-06 | None | None | None | None | N | None | 0 | 4.57247E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/R | None | None | 0.896 | N | 0.684 | 0.598 | 0.814266610154 | gnomAD-4.0.0 | 6.84139E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99399E-07 | 0 | 0 |
| I/T | rs1575194805 |
None | 0.016 | N | 0.392 | 0.368 | 0.673447929508 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/T | rs1575194805 |
None | 0.016 | N | 0.392 | 0.368 | 0.673447929508 | gnomAD-4.0.0 | 2.47842E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.39015E-06 | 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 | 0.4836 | ambiguous | 0.4547 | ambiguous | -2.214 | Highly Destabilizing | 0.25 | N | 0.511 | neutral | None | None | None | None | N |
| I/C | 0.8423 | likely_pathogenic | 0.8037 | pathogenic | -1.833 | Destabilizing | 0.977 | D | 0.616 | neutral | None | None | None | None | N |
| I/D | 0.8929 | likely_pathogenic | 0.879 | pathogenic | -2.066 | Highly Destabilizing | 0.92 | D | 0.664 | neutral | None | None | None | None | N |
| I/E | 0.8105 | likely_pathogenic | 0.7945 | pathogenic | -2.011 | Highly Destabilizing | 0.92 | D | 0.667 | neutral | None | None | None | None | N |
| I/F | 0.2287 | likely_benign | 0.2047 | benign | -1.653 | Destabilizing | 0.005 | N | 0.387 | neutral | None | None | None | None | N |
| I/G | 0.7941 | likely_pathogenic | 0.7645 | pathogenic | -2.604 | Highly Destabilizing | 0.766 | D | 0.618 | neutral | None | None | None | None | N |
| I/H | 0.7869 | likely_pathogenic | 0.7562 | pathogenic | -1.762 | Destabilizing | 0.992 | D | 0.647 | neutral | None | None | None | None | N |
| I/K | 0.6289 | likely_pathogenic | 0.5977 | pathogenic | -1.567 | Destabilizing | 0.896 | D | 0.666 | neutral | N | 0.481652076 | None | None | N |
| I/L | 0.1503 | likely_benign | 0.1375 | benign | -1.169 | Destabilizing | 0.099 | N | 0.378 | neutral | N | 0.479571776 | None | None | N |
| I/M | 0.1415 | likely_benign | 0.1258 | benign | -1.044 | Destabilizing | 0.81 | D | 0.606 | neutral | N | 0.481305359 | None | None | N |
| I/N | 0.5324 | ambiguous | 0.4961 | ambiguous | -1.543 | Destabilizing | 0.92 | D | 0.669 | neutral | None | None | None | None | N |
| I/P | 0.891 | likely_pathogenic | 0.8728 | pathogenic | -1.49 | Destabilizing | 0.972 | D | 0.667 | neutral | None | None | None | None | N |
| I/Q | 0.69 | likely_pathogenic | 0.6568 | pathogenic | -1.712 | Destabilizing | 0.972 | D | 0.685 | prob.neutral | None | None | None | None | N |
| I/R | 0.5238 | ambiguous | 0.4867 | ambiguous | -0.967 | Destabilizing | 0.896 | D | 0.684 | prob.neutral | N | 0.481478718 | None | None | N |
| I/S | 0.4801 | ambiguous | 0.453 | ambiguous | -2.252 | Highly Destabilizing | 0.447 | N | 0.566 | neutral | None | None | None | None | N |
| I/T | 0.4251 | ambiguous | 0.3945 | ambiguous | -2.068 | Highly Destabilizing | 0.016 | N | 0.392 | neutral | N | 0.480611926 | None | None | N |
| I/V | 0.0949 | likely_benign | 0.0907 | benign | -1.49 | Destabilizing | 0.002 | N | 0.15 | neutral | N | 0.455611907 | None | None | N |
| I/W | 0.8399 | likely_pathogenic | 0.8099 | pathogenic | -1.745 | Destabilizing | 0.992 | D | 0.639 | neutral | None | None | None | None | N |
| I/Y | 0.6768 | likely_pathogenic | 0.6404 | pathogenic | -1.52 | Destabilizing | 0.739 | D | 0.649 | 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.