Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32828 | 98707;98708;98709 | chr2:178539583;178539582;178539581 | chr2:179404310;179404309;179404308 |
| N2AB | 31187 | 93784;93785;93786 | chr2:178539583;178539582;178539581 | chr2:179404310;179404309;179404308 |
| N2A | 30260 | 91003;91004;91005 | chr2:178539583;178539582;178539581 | chr2:179404310;179404309;179404308 |
| N2B | 23763 | 71512;71513;71514 | chr2:178539583;178539582;178539581 | chr2:179404310;179404309;179404308 |
| Novex-1 | 23888 | 71887;71888;71889 | chr2:178539583;178539582;178539581 | chr2:179404310;179404309;179404308 |
| Novex-2 | 23955 | 72088;72089;72090 | chr2:178539583;178539582;178539581 | chr2:179404310;179404309;179404308 |
| 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/V | rs199689554  |
-1.349 | 0.003 | N | 0.229 | 0.139 | 0.471778926243 | gnomAD-2.1.1 | 4.28E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 6.14502E-04 | None | 0 | None | 0 | 0 | 0 |
| I/V | rs199689554 |
-1.349 | 0.003 | N | 0.229 | 0.139 | 0.471778926243 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 3.86698E-04 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs199689554 |
-1.349 | 0.003 | N | 0.229 | 0.139 | 0.471778926243 | gnomAD-4.0.0 | 1.67304E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.12706E-04 | None | 0 | 0 | 0 | 2.19582E-05 | 3.20102E-05 |
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 | 0.9571 | likely_pathogenic | 0.9349 | pathogenic | -2.261 | Highly Destabilizing | 0.404 | N | 0.718 | prob.delet. | None | None | None | None | N |
| I/C | 0.9453 | likely_pathogenic | 0.929 | pathogenic | -1.271 | Destabilizing | 0.973 | D | 0.755 | deleterious | None | None | None | None | N |
| I/D | 0.992 | likely_pathogenic | 0.9879 | pathogenic | -1.922 | Destabilizing | 0.906 | D | 0.86 | deleterious | None | None | None | None | N |
| I/E | 0.9876 | likely_pathogenic | 0.981 | pathogenic | -1.85 | Destabilizing | 0.906 | D | 0.861 | deleterious | None | None | None | None | N |
| I/F | 0.7338 | likely_pathogenic | 0.6938 | pathogenic | -1.545 | Destabilizing | 0.782 | D | 0.689 | prob.neutral | D | 0.542147325 | None | None | N |
| I/G | 0.9893 | likely_pathogenic | 0.9827 | pathogenic | -2.671 | Highly Destabilizing | 0.906 | D | 0.857 | deleterious | None | None | None | None | N |
| I/H | 0.9805 | likely_pathogenic | 0.9725 | pathogenic | -1.874 | Destabilizing | 0.991 | D | 0.826 | deleterious | None | None | None | None | N |
| I/K | 0.9734 | likely_pathogenic | 0.9603 | pathogenic | -1.625 | Destabilizing | 0.906 | D | 0.859 | deleterious | None | None | None | None | N |
| I/L | 0.3422 | ambiguous | 0.2937 | benign | -1.15 | Destabilizing | 0.001 | N | 0.214 | neutral | N | 0.484200483 | None | None | N |
| I/M | 0.4567 | ambiguous | 0.4134 | ambiguous | -0.783 | Destabilizing | 0.782 | D | 0.672 | neutral | D | 0.544682221 | None | None | N |
| I/N | 0.9018 | likely_pathogenic | 0.8547 | pathogenic | -1.522 | Destabilizing | 0.957 | D | 0.859 | deleterious | D | 0.530719022 | None | None | N |
| I/P | 0.9583 | likely_pathogenic | 0.9296 | pathogenic | -1.494 | Destabilizing | 0.967 | D | 0.864 | deleterious | None | None | None | None | N |
| I/Q | 0.9798 | likely_pathogenic | 0.9708 | pathogenic | -1.637 | Destabilizing | 0.967 | D | 0.855 | deleterious | None | None | None | None | N |
| I/R | 0.958 | likely_pathogenic | 0.9391 | pathogenic | -1.019 | Destabilizing | 0.906 | D | 0.862 | deleterious | None | None | None | None | N |
| I/S | 0.9305 | likely_pathogenic | 0.8956 | pathogenic | -2.188 | Highly Destabilizing | 0.782 | D | 0.828 | deleterious | D | 0.54493571 | None | None | N |
| I/T | 0.8938 | likely_pathogenic | 0.8455 | pathogenic | -1.993 | Destabilizing | 0.505 | D | 0.791 | deleterious | D | 0.526996039 | None | None | N |
| I/V | 0.1529 | likely_benign | 0.1381 | benign | -1.494 | Destabilizing | 0.003 | N | 0.229 | neutral | N | 0.472070482 | None | None | N |
| I/W | 0.9905 | likely_pathogenic | 0.9894 | pathogenic | -1.715 | Destabilizing | 0.991 | D | 0.809 | deleterious | None | None | None | None | N |
| I/Y | 0.9533 | likely_pathogenic | 0.9381 | pathogenic | -1.503 | Destabilizing | 0.906 | D | 0.781 | 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.