Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25228 | 75907;75908;75909 | chr2:178570450;178570449;178570448 | chr2:179435177;179435176;179435175 |
| N2AB | 23587 | 70984;70985;70986 | chr2:178570450;178570449;178570448 | chr2:179435177;179435176;179435175 |
| N2A | 22660 | 68203;68204;68205 | chr2:178570450;178570449;178570448 | chr2:179435177;179435176;179435175 |
| N2B | 16163 | 48712;48713;48714 | chr2:178570450;178570449;178570448 | chr2:179435177;179435176;179435175 |
| Novex-1 | 16288 | 49087;49088;49089 | chr2:178570450;178570449;178570448 | chr2:179435177;179435176;179435175 |
| Novex-2 | 16355 | 49288;49289;49290 | chr2:178570450;178570449;178570448 | chr2:179435177;179435176;179435175 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/S | rs377226540  |
-2.621 | 0.31 | N | 0.284 | 0.29 | None | gnomAD-2.1.1 | 1.0753E-04 | None | None | None | None | N | None | 1.20013E-03 | 0 | None | 0 | 0 | None | 0 | None | 0 | 7.86E-06 | 0 |
| P/S | rs377226540 |
-2.621 | 0.31 | N | 0.284 | 0.29 | None | gnomAD-3.1.2 | 2.69691E-04 | None | None | None | None | N | None | 9.89812E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/S | rs377226540 |
-2.621 | 0.31 | N | 0.284 | 0.29 | None | 1000 genomes | 5.99042E-04 | None | None | None | None | N | None | 2.3E-03 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| P/S | rs377226540 |
-2.621 | 0.31 | N | 0.284 | 0.29 | None | gnomAD-4.0.0 | 4.95903E-05 | None | None | None | None | N | None | 1.02678E-03 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 4.80492E-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 | 0.0872 | likely_benign | 0.087 | benign | -1.981 | Destabilizing | 0.061 | N | 0.254 | neutral | N | 0.473120439 | None | None | N |
| P/C | 0.5575 | ambiguous | 0.5572 | ambiguous | -1.312 | Destabilizing | 0.999 | D | 0.603 | neutral | None | None | None | None | N |
| P/D | 0.6899 | likely_pathogenic | 0.713 | pathogenic | -2.463 | Highly Destabilizing | 0.939 | D | 0.459 | neutral | None | None | None | None | N |
| P/E | 0.3541 | ambiguous | 0.3613 | ambiguous | -2.312 | Highly Destabilizing | 0.939 | D | 0.445 | neutral | None | None | None | None | N |
| P/F | 0.6003 | likely_pathogenic | 0.6074 | pathogenic | -1.366 | Destabilizing | 0.997 | D | 0.607 | neutral | None | None | None | None | N |
| P/G | 0.4374 | ambiguous | 0.4611 | ambiguous | -2.399 | Highly Destabilizing | 0.939 | D | 0.494 | neutral | None | None | None | None | N |
| P/H | 0.2721 | likely_benign | 0.2827 | benign | -1.863 | Destabilizing | 0.999 | D | 0.569 | neutral | N | 0.500876387 | None | None | N |
| P/I | 0.3382 | likely_benign | 0.329 | benign | -0.846 | Destabilizing | 0.982 | D | 0.603 | neutral | None | None | None | None | N |
| P/K | 0.2736 | likely_benign | 0.2969 | benign | -1.752 | Destabilizing | 0.939 | D | 0.456 | neutral | None | None | None | None | N |
| P/L | 0.1321 | likely_benign | 0.1333 | benign | -0.846 | Destabilizing | 0.92 | D | 0.517 | neutral | N | 0.502179833 | None | None | N |
| P/M | 0.2989 | likely_benign | 0.2927 | benign | -0.72 | Destabilizing | 0.999 | D | 0.571 | neutral | None | None | None | None | N |
| P/N | 0.5034 | ambiguous | 0.5214 | ambiguous | -1.885 | Destabilizing | 0.982 | D | 0.571 | neutral | None | None | None | None | N |
| P/Q | 0.1773 | likely_benign | 0.1835 | benign | -1.882 | Destabilizing | 0.991 | D | 0.547 | neutral | None | None | None | None | N |
| P/R | 0.203 | likely_benign | 0.2193 | benign | -1.367 | Destabilizing | 0.988 | D | 0.579 | neutral | N | 0.497811741 | None | None | N |
| P/S | 0.202 | likely_benign | 0.204 | benign | -2.391 | Highly Destabilizing | 0.31 | N | 0.284 | neutral | N | 0.499039508 | None | None | N |
| P/T | 0.1704 | likely_benign | 0.1642 | benign | -2.115 | Highly Destabilizing | 0.134 | N | 0.285 | neutral | N | 0.498634661 | None | None | N |
| P/V | 0.2202 | likely_benign | 0.216 | benign | -1.198 | Destabilizing | 0.939 | D | 0.479 | neutral | None | None | None | None | N |
| P/W | 0.7735 | likely_pathogenic | 0.7651 | pathogenic | -1.702 | Destabilizing | 0.999 | D | 0.651 | neutral | None | None | None | None | N |
| P/Y | 0.5149 | ambiguous | 0.5348 | ambiguous | -1.358 | Destabilizing | 0.997 | D | 0.607 | 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.