Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18700 | 56323;56324;56325 | chr2:178599803;178599802;178599801 | chr2:179464530;179464529;179464528 |
| N2AB | 17059 | 51400;51401;51402 | chr2:178599803;178599802;178599801 | chr2:179464530;179464529;179464528 |
| N2A | 16132 | 48619;48620;48621 | chr2:178599803;178599802;178599801 | chr2:179464530;179464529;179464528 |
| N2B | 9635 | 29128;29129;29130 | chr2:178599803;178599802;178599801 | chr2:179464530;179464529;179464528 |
| Novex-1 | 9760 | 29503;29504;29505 | chr2:178599803;178599802;178599801 | chr2:179464530;179464529;179464528 |
| Novex-2 | 9827 | 29704;29705;29706 | chr2:178599803;178599802;178599801 | chr2:179464530;179464529;179464528 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/N | None | None | 0.996 | N | 0.365 | 0.183 | 0.192905019026 | gnomAD-4.0.0 | 6.8795E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.18413E-05 | 0 |
| T/S | rs1265206285  |
-0.573 | 0.959 | N | 0.391 | 0.177 | 0.0716867268079 | gnomAD-2.1.1 | 4.12E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.04E-06 | 0 |
| T/S | rs1265206285 |
-0.573 | 0.959 | N | 0.391 | 0.177 | 0.0716867268079 | gnomAD-4.0.0 | 2.06385E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.80382E-06 | 0 | 1.66633E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0849 | likely_benign | 0.0886 | benign | -0.77 | Destabilizing | 0.826 | D | 0.366 | neutral | N | 0.42013303 | None | None | N |
| T/C | 0.3376 | likely_benign | 0.3552 | ambiguous | -0.518 | Destabilizing | 0.046 | N | 0.235 | neutral | None | None | None | None | N |
| T/D | 0.2921 | likely_benign | 0.3029 | benign | -0.464 | Destabilizing | 0.997 | D | 0.339 | neutral | None | None | None | None | N |
| T/E | 0.2133 | likely_benign | 0.2297 | benign | -0.502 | Destabilizing | 0.997 | D | 0.353 | neutral | None | None | None | None | N |
| T/F | 0.2859 | likely_benign | 0.2989 | benign | -1.181 | Destabilizing | 0.046 | N | 0.312 | neutral | None | None | None | None | N |
| T/G | 0.2153 | likely_benign | 0.2301 | benign | -0.951 | Destabilizing | 0.969 | D | 0.463 | neutral | None | None | None | None | N |
| T/H | 0.2499 | likely_benign | 0.2467 | benign | -1.376 | Destabilizing | 0.999 | D | 0.437 | neutral | None | None | None | None | N |
| T/I | 0.2393 | likely_benign | 0.2566 | benign | -0.391 | Destabilizing | 0.852 | D | 0.354 | neutral | N | 0.460794222 | None | None | N |
| T/K | 0.1609 | likely_benign | 0.17 | benign | -0.585 | Destabilizing | 0.969 | D | 0.381 | neutral | None | None | None | None | N |
| T/L | 0.1356 | likely_benign | 0.1472 | benign | -0.391 | Destabilizing | 0.759 | D | 0.397 | neutral | None | None | None | None | N |
| T/M | 0.1038 | likely_benign | 0.107 | benign | 0.093 | Stabilizing | 0.579 | D | 0.349 | neutral | None | None | None | None | N |
| T/N | 0.1136 | likely_benign | 0.1152 | benign | -0.517 | Destabilizing | 0.996 | D | 0.365 | neutral | N | 0.431464745 | None | None | N |
| T/P | 0.5772 | likely_pathogenic | 0.6589 | pathogenic | -0.488 | Destabilizing | 0.996 | D | 0.369 | neutral | N | 0.481701564 | None | None | N |
| T/Q | 0.1735 | likely_benign | 0.183 | benign | -0.836 | Destabilizing | 0.991 | D | 0.359 | neutral | None | None | None | None | N |
| T/R | 0.1568 | likely_benign | 0.1661 | benign | -0.289 | Destabilizing | 0.991 | D | 0.371 | neutral | None | None | None | None | N |
| T/S | 0.0993 | likely_benign | 0.0985 | benign | -0.747 | Destabilizing | 0.959 | D | 0.391 | neutral | N | 0.394157151 | None | None | N |
| T/V | 0.1699 | likely_benign | 0.1795 | benign | -0.488 | Destabilizing | 0.759 | D | 0.371 | neutral | None | None | None | None | N |
| T/W | 0.5973 | likely_pathogenic | 0.6192 | pathogenic | -1.098 | Destabilizing | 0.999 | D | 0.447 | neutral | None | None | None | None | N |
| T/Y | 0.3026 | likely_benign | 0.3207 | benign | -0.829 | Destabilizing | 0.964 | D | 0.443 | 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.