Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16095 | 48508;48509;48510 | chr2:178616508;178616507;178616506 | chr2:179481235;179481234;179481233 |
| N2AB | 14454 | 43585;43586;43587 | chr2:178616508;178616507;178616506 | chr2:179481235;179481234;179481233 |
| N2A | 13527 | 40804;40805;40806 | chr2:178616508;178616507;178616506 | chr2:179481235;179481234;179481233 |
| N2B | 7030 | 21313;21314;21315 | chr2:178616508;178616507;178616506 | chr2:179481235;179481234;179481233 |
| Novex-1 | 7155 | 21688;21689;21690 | chr2:178616508;178616507;178616506 | chr2:179481235;179481234;179481233 |
| Novex-2 | 7222 | 21889;21890;21891 | chr2:178616508;178616507;178616506 | chr2:179481235;179481234;179481233 |
| 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 | rs369453963  |
-1.039 | 0.999 | N | 0.511 | 0.324 | None | gnomAD-2.1.1 | 2.87E-05 | None | None | None | None | N | None | 8.29E-05 | 0 | None | 0 | 0 | None | 0 | None | 1.9984E-04 | 7.86E-06 | 0 |
| R/Q | rs369453963 |
-1.039 | 0.999 | N | 0.511 | 0.324 | None | gnomAD-3.1.2 | 1.98E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 1.88644E-04 | 0 | 1.47E-05 | 0 | 0 |
| R/Q | rs369453963 |
-1.039 | 0.999 | N | 0.511 | 0.324 | None | gnomAD-4.0.0 | 8.68408E-06 | None | None | None | None | N | None | 2.67465E-05 | 0 | None | 0 | 0 | None | 7.81348E-05 | 0 | 5.93796E-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 | 0.9809 | likely_pathogenic | 0.9724 | pathogenic | -2.248 | Highly Destabilizing | 0.91 | D | 0.535 | neutral | None | None | None | None | N |
| R/C | 0.6997 | likely_pathogenic | 0.6189 | pathogenic | -2.056 | Highly Destabilizing | 0.128 | N | 0.486 | neutral | None | None | None | None | N |
| R/D | 0.997 | likely_pathogenic | 0.9968 | pathogenic | -0.846 | Destabilizing | 0.998 | D | 0.742 | deleterious | None | None | None | None | N |
| R/E | 0.9648 | likely_pathogenic | 0.953 | pathogenic | -0.638 | Destabilizing | 0.992 | D | 0.481 | neutral | None | None | None | None | N |
| R/F | 0.9827 | likely_pathogenic | 0.9785 | pathogenic | -1.58 | Destabilizing | 0.998 | D | 0.795 | deleterious | None | None | None | None | N |
| R/G | 0.9639 | likely_pathogenic | 0.9543 | pathogenic | -2.58 | Highly Destabilizing | 0.987 | D | 0.643 | neutral | D | 0.641484036 | None | None | N |
| R/H | 0.6304 | likely_pathogenic | 0.5806 | pathogenic | -2.362 | Highly Destabilizing | 0.999 | D | 0.535 | neutral | None | None | None | None | N |
| R/I | 0.9692 | likely_pathogenic | 0.9518 | pathogenic | -1.28 | Destabilizing | 0.986 | D | 0.789 | deleterious | None | None | None | None | N |
| R/K | 0.362 | ambiguous | 0.3269 | benign | -1.415 | Destabilizing | 0.992 | D | 0.479 | neutral | None | None | None | None | N |
| R/L | 0.913 | likely_pathogenic | 0.8914 | pathogenic | -1.28 | Destabilizing | 0.951 | D | 0.621 | neutral | D | 0.586664594 | None | None | N |
| R/M | 0.9087 | likely_pathogenic | 0.8576 | pathogenic | -1.7 | Destabilizing | 0.999 | D | 0.676 | prob.neutral | None | None | None | None | N |
| R/N | 0.9865 | likely_pathogenic | 0.9847 | pathogenic | -1.278 | Destabilizing | 0.998 | D | 0.5 | neutral | None | None | None | None | N |
| R/P | 0.9991 | likely_pathogenic | 0.9991 | pathogenic | -1.593 | Destabilizing | 0.999 | D | 0.755 | deleterious | D | 0.738109088 | None | None | N |
| R/Q | 0.47 | ambiguous | 0.3638 | ambiguous | -1.251 | Destabilizing | 0.999 | D | 0.511 | neutral | N | 0.472508372 | None | None | N |
| R/S | 0.991 | likely_pathogenic | 0.9876 | pathogenic | -2.315 | Highly Destabilizing | 0.953 | D | 0.581 | neutral | None | None | None | None | N |
| R/T | 0.983 | likely_pathogenic | 0.9743 | pathogenic | -1.894 | Destabilizing | 0.953 | D | 0.592 | neutral | None | None | None | None | N |
| R/V | 0.9695 | likely_pathogenic | 0.9568 | pathogenic | -1.593 | Destabilizing | 0.986 | D | 0.727 | prob.delet. | None | None | None | None | N |
| R/W | 0.8293 | likely_pathogenic | 0.7941 | pathogenic | -1.002 | Destabilizing | 0.999 | D | 0.747 | deleterious | None | None | None | None | N |
| R/Y | 0.9325 | likely_pathogenic | 0.9225 | pathogenic | -0.892 | Destabilizing | 0.998 | D | 0.763 | deleterious | 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.