Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16099 | 48520;48521;48522 | chr2:178616496;178616495;178616494 | chr2:179481223;179481222;179481221 |
| N2AB | 14458 | 43597;43598;43599 | chr2:178616496;178616495;178616494 | chr2:179481223;179481222;179481221 |
| N2A | 13531 | 40816;40817;40818 | chr2:178616496;178616495;178616494 | chr2:179481223;179481222;179481221 |
| N2B | 7034 | 21325;21326;21327 | chr2:178616496;178616495;178616494 | chr2:179481223;179481222;179481221 |
| Novex-1 | 7159 | 21700;21701;21702 | chr2:178616496;178616495;178616494 | chr2:179481223;179481222;179481221 |
| Novex-2 | 7226 | 21901;21902;21903 | chr2:178616496;178616495;178616494 | chr2:179481223;179481222;179481221 |
| 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/Q | rs376747673  |
-0.14 | 1.0 | N | 0.645 | 0.3 | None | gnomAD-2.1.1 | 3.23E-05 | None | None | None | None | N | None | 1.24492E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 4.73E-05 | 0 |
| R/Q | rs376747673 |
-0.14 | 1.0 | N | 0.645 | 0.3 | None | gnomAD-3.1.2 | 4.61E-05 | None | None | None | None | N | None | 7.25E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 5.89E-05 | 0 | 0 |
| R/Q | rs376747673 |
-0.14 | 1.0 | N | 0.645 | 0.3 | None | gnomAD-4.0.0 | 6.82414E-05 | None | None | None | None | N | None | 8.0274E-05 | 0 | None | 3.38593E-05 | 0 | None | 0 | 0 | 7.97467E-05 | 2.19814E-05 | 1.12266E-04 |
| R/W | rs765526529 |
-0.576 | 1.0 | D | 0.743 | 0.419 | 0.353125101423 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 1.79E-05 | 0 |
| R/W | rs765526529 |
-0.576 | 1.0 | D | 0.743 | 0.419 | 0.353125101423 | gnomAD-3.1.2 | 6.59E-06 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/W | rs765526529 |
-0.576 | 1.0 | D | 0.743 | 0.419 | 0.353125101423 | gnomAD-4.0.0 | 1.61313E-05 | None | None | None | None | N | None | 1.33894E-05 | 1.67051E-05 | None | 0 | 0 | None | 0 | 3.29815E-04 | 1.61196E-05 | 3.29801E-05 | 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 | 0.9103 | likely_pathogenic | 0.8641 | pathogenic | -0.713 | Destabilizing | 0.999 | D | 0.483 | neutral | None | None | None | None | N |
| R/C | 0.6048 | likely_pathogenic | 0.4643 | ambiguous | -0.681 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | N |
| R/D | 0.9738 | likely_pathogenic | 0.9628 | pathogenic | -0.092 | Destabilizing | 1.0 | D | 0.614 | neutral | None | None | None | None | N |
| R/E | 0.8888 | likely_pathogenic | 0.8436 | pathogenic | -0.015 | Destabilizing | 0.999 | D | 0.533 | neutral | None | None | None | None | N |
| R/F | 0.9493 | likely_pathogenic | 0.924 | pathogenic | -0.829 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | N |
| R/G | 0.8232 | likely_pathogenic | 0.7156 | pathogenic | -0.954 | Destabilizing | 1.0 | D | 0.523 | neutral | N | 0.468954579 | None | None | N |
| R/H | 0.4051 | ambiguous | 0.3278 | benign | -1.219 | Destabilizing | 1.0 | D | 0.69 | prob.neutral | None | None | None | None | N |
| R/I | 0.9057 | likely_pathogenic | 0.8483 | pathogenic | -0.088 | Destabilizing | 1.0 | D | 0.692 | prob.neutral | None | None | None | None | N |
| R/K | 0.3203 | likely_benign | 0.2491 | benign | -0.723 | Destabilizing | 0.998 | D | 0.427 | neutral | None | None | None | None | N |
| R/L | 0.7871 | likely_pathogenic | 0.6939 | pathogenic | -0.088 | Destabilizing | 1.0 | D | 0.523 | neutral | D | 0.562808417 | None | None | N |
| R/M | 0.8739 | likely_pathogenic | 0.7871 | pathogenic | -0.269 | Destabilizing | 1.0 | D | 0.663 | neutral | None | None | None | None | N |
| R/N | 0.9559 | likely_pathogenic | 0.9362 | pathogenic | -0.154 | Destabilizing | 1.0 | D | 0.648 | neutral | None | None | None | None | N |
| R/P | 0.981 | likely_pathogenic | 0.9672 | pathogenic | -0.277 | Destabilizing | 1.0 | D | 0.619 | neutral | D | 0.539097618 | None | None | N |
| R/Q | 0.3944 | ambiguous | 0.2848 | benign | -0.431 | Destabilizing | 1.0 | D | 0.645 | neutral | N | 0.504031601 | None | None | N |
| R/S | 0.9348 | likely_pathogenic | 0.9018 | pathogenic | -0.885 | Destabilizing | 1.0 | D | 0.587 | neutral | None | None | None | None | N |
| R/T | 0.8784 | likely_pathogenic | 0.8088 | pathogenic | -0.656 | Destabilizing | 1.0 | D | 0.587 | neutral | None | None | None | None | N |
| R/V | 0.9051 | likely_pathogenic | 0.858 | pathogenic | -0.277 | Destabilizing | 1.0 | D | 0.659 | neutral | None | None | None | None | N |
| R/W | 0.6568 | likely_pathogenic | 0.52 | ambiguous | -0.574 | Destabilizing | 1.0 | D | 0.743 | deleterious | D | 0.535751051 | None | None | N |
| R/Y | 0.8854 | likely_pathogenic | 0.8439 | pathogenic | -0.242 | Destabilizing | 1.0 | D | 0.661 | 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.