Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22107 | 66544;66545;66546 | chr2:178582050;178582049;178582048 | chr2:179446777;179446776;179446775 |
| N2AB | 20466 | 61621;61622;61623 | chr2:178582050;178582049;178582048 | chr2:179446777;179446776;179446775 |
| N2A | 19539 | 58840;58841;58842 | chr2:178582050;178582049;178582048 | chr2:179446777;179446776;179446775 |
| N2B | 13042 | 39349;39350;39351 | chr2:178582050;178582049;178582048 | chr2:179446777;179446776;179446775 |
| Novex-1 | 13167 | 39724;39725;39726 | chr2:178582050;178582049;178582048 | chr2:179446777;179446776;179446775 |
| Novex-2 | 13234 | 39925;39926;39927 | chr2:178582050;178582049;178582048 | chr2:179446777;179446776;179446775 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/K | rs548035555  |
0.22 | 0.025 | N | 0.37 | 0.185 | 0.190952846119 | gnomAD-2.1.1 | 7.15E-06 | None | None | None | None | I | None | 8.28E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/K | rs548035555 |
0.22 | 0.025 | N | 0.37 | 0.185 | 0.190952846119 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 7.24E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/K | rs548035555 |
0.22 | 0.025 | N | 0.37 | 0.185 | 0.190952846119 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/K | rs548035555 |
0.22 | 0.025 | N | 0.37 | 0.185 | 0.190952846119 | gnomAD-4.0.0 | 5.12673E-06 | None | None | None | None | I | None | 5.06825E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.39462E-06 | 0 | 0 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9276 | likely_pathogenic | 0.8379 | pathogenic | 0.156 | Stabilizing | 0.845 | D | 0.57 | neutral | None | None | None | None | I |
| R/C | 0.7357 | likely_pathogenic | 0.5691 | pathogenic | -0.057 | Destabilizing | 0.999 | D | 0.617 | neutral | None | None | None | None | I |
| R/D | 0.9605 | likely_pathogenic | 0.9244 | pathogenic | -0.202 | Destabilizing | 0.975 | D | 0.526 | neutral | None | None | None | None | I |
| R/E | 0.9043 | likely_pathogenic | 0.8071 | pathogenic | -0.152 | Destabilizing | 0.845 | D | 0.571 | neutral | None | None | None | None | I |
| R/F | 0.9609 | likely_pathogenic | 0.9149 | pathogenic | -0.123 | Destabilizing | 0.996 | D | 0.582 | neutral | None | None | None | None | I |
| R/G | 0.8041 | likely_pathogenic | 0.6349 | pathogenic | -0.002 | Destabilizing | 0.892 | D | 0.449 | neutral | N | 0.507456519 | None | None | I |
| R/H | 0.399 | ambiguous | 0.2707 | benign | -0.55 | Destabilizing | 0.987 | D | 0.568 | neutral | None | None | None | None | I |
| R/I | 0.8785 | likely_pathogenic | 0.7577 | pathogenic | 0.528 | Stabilizing | 0.983 | D | 0.586 | neutral | N | 0.496679378 | None | None | I |
| R/K | 0.2331 | likely_benign | 0.1785 | benign | 0.032 | Stabilizing | 0.025 | N | 0.37 | neutral | N | 0.409967257 | None | None | I |
| R/L | 0.8312 | likely_pathogenic | 0.7004 | pathogenic | 0.528 | Stabilizing | 0.916 | D | 0.449 | neutral | None | None | None | None | I |
| R/M | 0.8945 | likely_pathogenic | 0.7577 | pathogenic | 0.041 | Stabilizing | 0.999 | D | 0.53 | neutral | None | None | None | None | I |
| R/N | 0.9444 | likely_pathogenic | 0.8906 | pathogenic | 0.173 | Stabilizing | 0.975 | D | 0.55 | neutral | None | None | None | None | I |
| R/P | 0.9051 | likely_pathogenic | 0.8251 | pathogenic | 0.423 | Stabilizing | 0.987 | D | 0.529 | neutral | None | None | None | None | I |
| R/Q | 0.3994 | ambiguous | 0.256 | benign | 0.126 | Stabilizing | 0.975 | D | 0.569 | neutral | None | None | None | None | I |
| R/S | 0.9377 | likely_pathogenic | 0.8683 | pathogenic | -0.013 | Destabilizing | 0.892 | D | 0.531 | neutral | N | 0.463665669 | None | None | I |
| R/T | 0.8757 | likely_pathogenic | 0.7227 | pathogenic | 0.149 | Stabilizing | 0.967 | D | 0.514 | neutral | N | 0.436209709 | None | None | I |
| R/V | 0.9064 | likely_pathogenic | 0.8156 | pathogenic | 0.423 | Stabilizing | 0.975 | D | 0.587 | neutral | None | None | None | None | I |
| R/W | 0.661 | likely_pathogenic | 0.4619 | ambiguous | -0.295 | Destabilizing | 0.999 | D | 0.645 | neutral | None | None | None | None | I |
| R/Y | 0.8616 | likely_pathogenic | 0.7595 | pathogenic | 0.121 | Stabilizing | 0.996 | D | 0.533 | neutral | None | None | None | None | I |
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.