Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28377 | 85354;85355;85356 | chr2:178561003;178561002;178561001 | chr2:179425730;179425729;179425728 |
| N2AB | 26736 | 80431;80432;80433 | chr2:178561003;178561002;178561001 | chr2:179425730;179425729;179425728 |
| N2A | 25809 | 77650;77651;77652 | chr2:178561003;178561002;178561001 | chr2:179425730;179425729;179425728 |
| N2B | 19312 | 58159;58160;58161 | chr2:178561003;178561002;178561001 | chr2:179425730;179425729;179425728 |
| Novex-1 | 19437 | 58534;58535;58536 | chr2:178561003;178561002;178561001 | chr2:179425730;179425729;179425728 |
| Novex-2 | 19504 | 58735;58736;58737 | chr2:178561003;178561002;178561001 | chr2:179425730;179425729;179425728 |
| 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/T | rs876658089  |
-2.743 | 0.684 | D | 0.731 | 0.528 | 0.758086412925 | gnomAD-2.1.1 | 7.15E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.02491E-04 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs876658089 |
-2.743 | 0.684 | D | 0.731 | 0.528 | 0.758086412925 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 3.85802E-04 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs876658089 |
-2.743 | 0.684 | D | 0.731 | 0.528 | 0.758086412925 | gnomAD-4.0.0 | 5.12418E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 7.27308E-05 | None | 0 | 0 | 0 | 0 | 2.84414E-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 | 0.9658 | likely_pathogenic | 0.9593 | pathogenic | -2.186 | Highly Destabilizing | 0.59 | D | 0.69 | prob.neutral | None | None | None | None | N |
| I/C | 0.9538 | likely_pathogenic | 0.9495 | pathogenic | -1.46 | Destabilizing | 0.996 | D | 0.763 | deleterious | None | None | None | None | N |
| I/D | 0.9969 | likely_pathogenic | 0.9963 | pathogenic | -2.972 | Highly Destabilizing | 0.984 | D | 0.854 | deleterious | None | None | None | None | N |
| I/E | 0.9921 | likely_pathogenic | 0.9907 | pathogenic | -2.698 | Highly Destabilizing | 0.953 | D | 0.85 | deleterious | None | None | None | None | N |
| I/F | 0.3621 | ambiguous | 0.3717 | ambiguous | -1.482 | Destabilizing | 0.02 | N | 0.403 | neutral | None | None | None | None | N |
| I/G | 0.9895 | likely_pathogenic | 0.9878 | pathogenic | -2.685 | Highly Destabilizing | 0.953 | D | 0.827 | deleterious | None | None | None | None | N |
| I/H | 0.9869 | likely_pathogenic | 0.9838 | pathogenic | -2.395 | Highly Destabilizing | 0.996 | D | 0.847 | deleterious | None | None | None | None | N |
| I/K | 0.981 | likely_pathogenic | 0.9757 | pathogenic | -1.728 | Destabilizing | 0.939 | D | 0.84 | deleterious | D | 0.523524362 | None | None | N |
| I/L | 0.1584 | likely_benign | 0.151 | benign | -0.692 | Destabilizing | 0.003 | N | 0.295 | neutral | N | 0.388591907 | None | None | N |
| I/M | 0.1782 | likely_benign | 0.1661 | benign | -0.779 | Destabilizing | 0.884 | D | 0.665 | neutral | D | 0.52824837 | None | None | N |
| I/N | 0.968 | likely_pathogenic | 0.9604 | pathogenic | -2.367 | Highly Destabilizing | 0.984 | D | 0.856 | deleterious | None | None | None | None | N |
| I/P | 0.995 | likely_pathogenic | 0.9936 | pathogenic | -1.181 | Destabilizing | 0.984 | D | 0.856 | deleterious | None | None | None | None | N |
| I/Q | 0.9832 | likely_pathogenic | 0.9797 | pathogenic | -2.066 | Highly Destabilizing | 0.984 | D | 0.86 | deleterious | None | None | None | None | N |
| I/R | 0.9746 | likely_pathogenic | 0.9676 | pathogenic | -1.864 | Destabilizing | 0.939 | D | 0.856 | deleterious | D | 0.523524362 | None | None | N |
| I/S | 0.9821 | likely_pathogenic | 0.9776 | pathogenic | -2.833 | Highly Destabilizing | 0.953 | D | 0.802 | deleterious | None | None | None | None | N |
| I/T | 0.9842 | likely_pathogenic | 0.9784 | pathogenic | -2.407 | Highly Destabilizing | 0.684 | D | 0.731 | prob.delet. | D | 0.523270873 | None | None | N |
| I/V | 0.2314 | likely_benign | 0.2143 | benign | -1.181 | Destabilizing | 0.007 | N | 0.277 | neutral | D | 0.534174265 | None | None | N |
| I/W | 0.9477 | likely_pathogenic | 0.9451 | pathogenic | -1.815 | Destabilizing | 0.996 | D | 0.839 | deleterious | None | None | None | None | N |
| I/Y | 0.857 | likely_pathogenic | 0.8536 | pathogenic | -1.543 | Destabilizing | 0.835 | D | 0.751 | 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.