Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1598 | 5017;5018;5019 | chr2:178777171;178777170;178777169 | chr2:179641898;179641897;179641896 |
| N2AB | 1598 | 5017;5018;5019 | chr2:178777171;178777170;178777169 | chr2:179641898;179641897;179641896 |
| N2A | 1598 | 5017;5018;5019 | chr2:178777171;178777170;178777169 | chr2:179641898;179641897;179641896 |
| N2B | 1552 | 4879;4880;4881 | chr2:178777171;178777170;178777169 | chr2:179641898;179641897;179641896 |
| Novex-1 | 1552 | 4879;4880;4881 | chr2:178777171;178777170;178777169 | chr2:179641898;179641897;179641896 |
| Novex-2 | 1552 | 4879;4880;4881 | chr2:178777171;178777170;178777169 | chr2:179641898;179641897;179641896 |
| Novex-3 | 1598 | 5017;5018;5019 | chr2:178777171;178777170;178777169 | chr2:179641898;179641897;179641896 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | None | None | 0.999 | D | 0.751 | 0.479 | 0.814722147942 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| P/S | rs778940810  |
-2.215 | 0.957 | N | 0.338 | 0.398 | 0.497021753114 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.81E-06 | 0 |
| P/S | rs778940810 |
-2.215 | 0.957 | N | 0.338 | 0.398 | 0.497021753114 | gnomAD-4.0.0 | 3.42052E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.59731E-06 | 0 | 1.65585E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.2558 | likely_benign | 0.2239 | benign | -0.83 | Destabilizing | 0.992 | D | 0.513 | neutral | D | 0.531478282 | None | None | N |
| P/C | 0.9518 | likely_pathogenic | 0.9231 | pathogenic | -0.493 | Destabilizing | 1.0 | D | 0.76 | deleterious | None | None | None | None | N |
| P/D | 0.908 | likely_pathogenic | 0.8787 | pathogenic | -0.936 | Destabilizing | 0.999 | D | 0.713 | prob.delet. | None | None | None | None | N |
| P/E | 0.7523 | likely_pathogenic | 0.685 | pathogenic | -1.018 | Destabilizing | 0.999 | D | 0.706 | prob.neutral | None | None | None | None | N |
| P/F | 0.9408 | likely_pathogenic | 0.9119 | pathogenic | -0.874 | Destabilizing | 1.0 | D | 0.785 | deleterious | None | None | None | None | N |
| P/G | 0.7338 | likely_pathogenic | 0.6777 | pathogenic | -1.028 | Destabilizing | 0.997 | D | 0.655 | neutral | None | None | None | None | N |
| P/H | 0.6363 | likely_pathogenic | 0.5768 | pathogenic | -0.661 | Destabilizing | 1.0 | D | 0.747 | deleterious | D | 0.551950384 | None | None | N |
| P/I | 0.8831 | likely_pathogenic | 0.8246 | pathogenic | -0.429 | Destabilizing | 1.0 | D | 0.793 | deleterious | None | None | None | None | N |
| P/K | 0.8258 | likely_pathogenic | 0.7749 | pathogenic | -0.845 | Destabilizing | 0.999 | D | 0.699 | prob.neutral | None | None | None | None | N |
| P/L | 0.5073 | ambiguous | 0.4379 | ambiguous | -0.429 | Destabilizing | 0.999 | D | 0.751 | deleterious | D | 0.531550939 | None | None | N |
| P/M | 0.8451 | likely_pathogenic | 0.7874 | pathogenic | -0.337 | Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | N |
| P/N | 0.827 | likely_pathogenic | 0.7644 | pathogenic | -0.486 | Destabilizing | 0.999 | D | 0.748 | deleterious | None | None | None | None | N |
| P/Q | 0.5222 | ambiguous | 0.4724 | ambiguous | -0.733 | Destabilizing | 1.0 | D | 0.785 | deleterious | None | None | None | None | N |
| P/R | 0.646 | likely_pathogenic | 0.5894 | pathogenic | -0.269 | Destabilizing | 0.999 | D | 0.776 | deleterious | D | 0.603548746 | None | None | N |
| P/S | 0.3966 | ambiguous | 0.3391 | benign | -0.798 | Destabilizing | 0.957 | D | 0.338 | neutral | N | 0.501678412 | None | None | N |
| P/T | 0.4646 | ambiguous | 0.3889 | ambiguous | -0.788 | Destabilizing | 0.998 | D | 0.696 | prob.neutral | N | 0.504674529 | None | None | N |
| P/V | 0.77 | likely_pathogenic | 0.6966 | pathogenic | -0.528 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | N |
| P/W | 0.9661 | likely_pathogenic | 0.95 | pathogenic | -1.017 | Destabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | N |
| P/Y | 0.9217 | likely_pathogenic | 0.8882 | pathogenic | -0.737 | Destabilizing | 1.0 | D | 0.786 | 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.