Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31120 | 93583;93584;93585 | chr2:178548268;178548267;178548266 | chr2:179412995;179412994;179412993 |
| N2AB | 29479 | 88660;88661;88662 | chr2:178548268;178548267;178548266 | chr2:179412995;179412994;179412993 |
| N2A | 28552 | 85879;85880;85881 | chr2:178548268;178548267;178548266 | chr2:179412995;179412994;179412993 |
| N2B | 22055 | 66388;66389;66390 | chr2:178548268;178548267;178548266 | chr2:179412995;179412994;179412993 |
| Novex-1 | 22180 | 66763;66764;66765 | chr2:178548268;178548267;178548266 | chr2:179412995;179412994;179412993 |
| Novex-2 | 22247 | 66964;66965;66966 | chr2:178548268;178548267;178548266 | chr2:179412995;179412994;179412993 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/F | rs1698000478  |
None | 1.0 | N | 0.853 | 0.436 | 0.62347134366 | gnomAD-4.0.0 | 2.05255E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.51902E-05 | None | 0 | 1.7343E-04 | 8.99437E-07 | 0 | 0 |
| L/P | rs1310673663 |
-1.975 | 1.0 | N | 0.905 | 0.647 | 0.62428156105 | gnomAD-2.1.1 | 7.15E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.57E-05 | 0 |
| L/P | rs1310673663 |
-1.975 | 1.0 | N | 0.905 | 0.647 | 0.62428156105 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 5.88E-05 | 0 | 0 |
| L/P | rs1310673663 |
-1.975 | 1.0 | N | 0.905 | 0.647 | 0.62428156105 | gnomAD-4.0.0 | 8.96709E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.67499E-05 | 0 | 0 |
| L/R | rs1310673663 |
-1.918 | 1.0 | D | 0.903 | 0.73 | 0.694925966178 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| L/R | rs1310673663 |
-1.918 | 1.0 | D | 0.903 | 0.73 | 0.694925966178 | gnomAD-4.0.0 | 1.5911E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85796E-06 | 0 | 0 |
| L/V | rs1698000478 |
None | 0.999 | N | 0.653 | 0.29 | 0.525102498511 | gnomAD-4.0.0 | 6.84183E-07 | None | None | None | None | N | None | 2.98757E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.8946 | likely_pathogenic | 0.8792 | pathogenic | -2.829 | Highly Destabilizing | 0.999 | D | 0.765 | deleterious | None | None | None | None | N |
| L/C | 0.8602 | likely_pathogenic | 0.8469 | pathogenic | -2.316 | Highly Destabilizing | 1.0 | D | 0.842 | deleterious | None | None | None | None | N |
| L/D | 0.9993 | likely_pathogenic | 0.999 | pathogenic | -3.657 | Highly Destabilizing | 1.0 | D | 0.906 | deleterious | None | None | None | None | N |
| L/E | 0.9959 | likely_pathogenic | 0.9941 | pathogenic | -3.413 | Highly Destabilizing | 1.0 | D | 0.894 | deleterious | None | None | None | None | N |
| L/F | 0.8233 | likely_pathogenic | 0.7879 | pathogenic | -1.595 | Destabilizing | 1.0 | D | 0.853 | deleterious | N | 0.498526665 | None | None | N |
| L/G | 0.986 | likely_pathogenic | 0.9828 | pathogenic | -3.371 | Highly Destabilizing | 1.0 | D | 0.886 | deleterious | None | None | None | None | N |
| L/H | 0.9942 | likely_pathogenic | 0.9918 | pathogenic | -2.908 | Highly Destabilizing | 1.0 | D | 0.855 | deleterious | D | 0.538573516 | None | None | N |
| L/I | 0.1858 | likely_benign | 0.1788 | benign | -1.233 | Destabilizing | 0.999 | D | 0.655 | neutral | N | 0.521991615 | None | None | N |
| L/K | 0.9953 | likely_pathogenic | 0.9925 | pathogenic | -2.352 | Highly Destabilizing | 1.0 | D | 0.883 | deleterious | None | None | None | None | N |
| L/M | 0.3337 | likely_benign | 0.3317 | benign | -1.394 | Destabilizing | 1.0 | D | 0.817 | deleterious | None | None | None | None | N |
| L/N | 0.9946 | likely_pathogenic | 0.993 | pathogenic | -2.81 | Highly Destabilizing | 1.0 | D | 0.908 | deleterious | None | None | None | None | N |
| L/P | 0.9872 | likely_pathogenic | 0.9744 | pathogenic | -1.751 | Destabilizing | 1.0 | D | 0.905 | deleterious | N | 0.480048992 | None | None | N |
| L/Q | 0.9858 | likely_pathogenic | 0.9811 | pathogenic | -2.626 | Highly Destabilizing | 1.0 | D | 0.909 | deleterious | None | None | None | None | N |
| L/R | 0.9897 | likely_pathogenic | 0.9841 | pathogenic | -2.065 | Highly Destabilizing | 1.0 | D | 0.903 | deleterious | D | 0.538573516 | None | None | N |
| L/S | 0.9878 | likely_pathogenic | 0.9851 | pathogenic | -3.397 | Highly Destabilizing | 1.0 | D | 0.874 | deleterious | None | None | None | None | N |
| L/T | 0.8902 | likely_pathogenic | 0.8723 | pathogenic | -3.017 | Highly Destabilizing | 1.0 | D | 0.849 | deleterious | None | None | None | None | N |
| L/V | 0.1474 | likely_benign | 0.1414 | benign | -1.751 | Destabilizing | 0.999 | D | 0.653 | neutral | N | 0.48548931 | None | None | N |
| L/W | 0.9828 | likely_pathogenic | 0.9725 | pathogenic | -2.087 | Highly Destabilizing | 1.0 | D | 0.8 | deleterious | None | None | None | None | N |
| L/Y | 0.9898 | likely_pathogenic | 0.9853 | pathogenic | -1.854 | Destabilizing | 1.0 | D | 0.874 | deleterious | 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.