Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16107 | 48544;48545;48546 | chr2:178615782;178615781;178615780 | chr2:179480509;179480508;179480507 |
| N2AB | 14466 | 43621;43622;43623 | chr2:178615782;178615781;178615780 | chr2:179480509;179480508;179480507 |
| N2A | 13539 | 40840;40841;40842 | chr2:178615782;178615781;178615780 | chr2:179480509;179480508;179480507 |
| N2B | 7042 | 21349;21350;21351 | chr2:178615782;178615781;178615780 | chr2:179480509;179480508;179480507 |
| Novex-1 | 7167 | 21724;21725;21726 | chr2:178615782;178615781;178615780 | chr2:179480509;179480508;179480507 |
| Novex-2 | 7234 | 21925;21926;21927 | chr2:178615782;178615781;178615780 | chr2:179480509;179480508;179480507 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/G | rs775805942  |
None | 0.801 | N | 0.307 | 0.195 | 0.236278675362 | gnomAD-3.1.2 | 1.98E-05 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.95E-05 | 0 | 0 |
| D/G | rs775805942 |
None | 0.801 | N | 0.307 | 0.195 | 0.236278675362 | gnomAD-4.0.0 | 2.79629E-05 | None | None | None | None | N | None | 1.34027E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 3.48047E-05 | 0 | 4.82021E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.2591 | likely_benign | 0.283 | benign | -0.388 | Destabilizing | 0.454 | N | 0.299 | neutral | N | 0.457904476 | None | None | N |
| D/C | 0.7477 | likely_pathogenic | 0.7963 | pathogenic | -0.193 | Destabilizing | 0.998 | D | 0.387 | neutral | None | None | None | None | N |
| D/E | 0.1953 | likely_benign | 0.2195 | benign | -0.404 | Destabilizing | 0.005 | N | 0.095 | neutral | N | 0.433838367 | None | None | N |
| D/F | 0.8243 | likely_pathogenic | 0.8325 | pathogenic | -0.007 | Destabilizing | 0.991 | D | 0.382 | neutral | None | None | None | None | N |
| D/G | 0.2401 | likely_benign | 0.2712 | benign | -0.673 | Destabilizing | 0.801 | D | 0.307 | neutral | N | 0.476811759 | None | None | N |
| D/H | 0.4418 | ambiguous | 0.4998 | ambiguous | -0.043 | Destabilizing | 0.966 | D | 0.351 | neutral | N | 0.473298071 | None | None | N |
| D/I | 0.6477 | likely_pathogenic | 0.66 | pathogenic | 0.338 | Stabilizing | 0.949 | D | 0.415 | neutral | None | None | None | None | N |
| D/K | 0.5834 | likely_pathogenic | 0.6318 | pathogenic | -0.068 | Destabilizing | 0.728 | D | 0.309 | neutral | None | None | None | None | N |
| D/L | 0.5994 | likely_pathogenic | 0.6241 | pathogenic | 0.338 | Stabilizing | 0.842 | D | 0.369 | neutral | None | None | None | None | N |
| D/M | 0.7895 | likely_pathogenic | 0.8164 | pathogenic | 0.5 | Stabilizing | 0.998 | D | 0.377 | neutral | None | None | None | None | N |
| D/N | 0.1564 | likely_benign | 0.1829 | benign | -0.471 | Destabilizing | 0.801 | D | 0.283 | neutral | N | 0.473422957 | None | None | N |
| D/P | 0.5962 | likely_pathogenic | 0.637 | pathogenic | 0.12 | Stabilizing | 0.974 | D | 0.341 | neutral | None | None | None | None | N |
| D/Q | 0.5001 | ambiguous | 0.5542 | ambiguous | -0.378 | Destabilizing | 0.728 | D | 0.325 | neutral | None | None | None | None | N |
| D/R | 0.603 | likely_pathogenic | 0.6455 | pathogenic | 0.194 | Stabilizing | 0.949 | D | 0.357 | neutral | None | None | None | None | N |
| D/S | 0.1838 | likely_benign | 0.2064 | benign | -0.644 | Destabilizing | 0.172 | N | 0.149 | neutral | None | None | None | None | N |
| D/T | 0.3636 | ambiguous | 0.4004 | ambiguous | -0.417 | Destabilizing | 0.029 | N | 0.162 | neutral | None | None | None | None | N |
| D/V | 0.4066 | ambiguous | 0.4157 | ambiguous | 0.12 | Stabilizing | 0.801 | D | 0.373 | neutral | N | 0.46714609 | None | None | N |
| D/W | 0.9337 | likely_pathogenic | 0.9405 | pathogenic | 0.193 | Stabilizing | 0.998 | D | 0.545 | neutral | None | None | None | None | N |
| D/Y | 0.4055 | ambiguous | 0.4211 | ambiguous | 0.236 | Stabilizing | 0.989 | D | 0.385 | neutral | N | 0.49713706 | 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.