Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29505 | 88738;88739;88740 | chr2:178554946;178554945;178554944 | chr2:179419673;179419672;179419671 |
| N2AB | 27864 | 83815;83816;83817 | chr2:178554946;178554945;178554944 | chr2:179419673;179419672;179419671 |
| N2A | 26937 | 81034;81035;81036 | chr2:178554946;178554945;178554944 | chr2:179419673;179419672;179419671 |
| N2B | 20440 | 61543;61544;61545 | chr2:178554946;178554945;178554944 | chr2:179419673;179419672;179419671 |
| Novex-1 | 20565 | 61918;61919;61920 | chr2:178554946;178554945;178554944 | chr2:179419673;179419672;179419671 |
| Novex-2 | 20632 | 62119;62120;62121 | chr2:178554946;178554945;178554944 | chr2:179419673;179419672;179419671 |
| 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/C | rs372360369  |
0.005 | 1.0 | N | 0.749 | 0.367 | None | gnomAD-2.1.1 | 2.5E-05 | None | None | None | None | N | None | 2.06594E-04 | 0 | None | 0 | 5.15E-05 | None | 0 | None | 0 | 7.82E-06 | 0 |
| R/C | rs372360369 |
0.005 | 1.0 | N | 0.749 | 0.367 | None | gnomAD-3.1.2 | 4.6E-05 | None | None | None | None | N | None | 1.44767E-04 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/C | rs372360369 |
0.005 | 1.0 | N | 0.749 | 0.367 | None | gnomAD-4.0.0 | 2.10706E-05 | None | None | None | None | N | None | 2.93631E-04 | 5.00133E-05 | None | 0 | 0 | None | 0 | 0 | 7.62833E-06 | 0 | 0 |
| R/G | None | None | 1.0 | N | 0.58 | 0.341 | 0.436239592564 | gnomAD-4.0.0 | 6.84236E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99449E-07 | 0 | 0 |
| R/H | rs143193258 |
-0.631 | 1.0 | N | 0.75 | 0.368 | None | gnomAD-2.1.1 | 8.93E-05 | None | None | None | None | N | None | 0 | 6.22912E-04 | None | 0 | 0 | None | 0 | None | 0 | 2.35E-05 | 0 |
| R/H | rs143193258 |
-0.631 | 1.0 | N | 0.75 | 0.368 | None | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 0 | 1.96464E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07211E-04 | 0 |
| R/H | rs143193258 |
-0.631 | 1.0 | N | 0.75 | 0.368 | None | 1000 genomes | 3.99361E-04 | None | None | None | None | N | None | 0 | 2.9E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/H | rs143193258 |
-0.631 | 1.0 | N | 0.75 | 0.368 | None | gnomAD-4.0.0 | 4.39959E-05 | None | None | None | None | N | None | 2.66475E-05 | 4.16597E-04 | None | 0 | 0 | None | 0 | 0 | 3.39036E-05 | 4.39194E-05 | 0 |
| R/S | None | None | 1.0 | N | 0.631 | 0.343 | 0.275641507738 | gnomAD-4.0.0 | 6.84236E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65678E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9598 | likely_pathogenic | 0.9619 | pathogenic | -0.502 | Destabilizing | 0.999 | D | 0.586 | neutral | None | None | None | None | N |
| R/C | 0.6776 | likely_pathogenic | 0.6939 | pathogenic | -0.548 | Destabilizing | 1.0 | D | 0.749 | deleterious | N | 0.475165949 | None | None | N |
| R/D | 0.9865 | likely_pathogenic | 0.9887 | pathogenic | 0.009 | Stabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | N |
| R/E | 0.9177 | likely_pathogenic | 0.9277 | pathogenic | 0.112 | Stabilizing | 0.999 | D | 0.625 | neutral | None | None | None | None | N |
| R/F | 0.973 | likely_pathogenic | 0.9725 | pathogenic | -0.492 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | N |
| R/G | 0.9323 | likely_pathogenic | 0.9348 | pathogenic | -0.773 | Destabilizing | 1.0 | D | 0.58 | neutral | N | 0.47465897 | None | None | N |
| R/H | 0.5178 | ambiguous | 0.4925 | ambiguous | -1.136 | Destabilizing | 1.0 | D | 0.75 | deleterious | N | 0.514334058 | None | None | N |
| R/I | 0.8693 | likely_pathogenic | 0.8792 | pathogenic | 0.206 | Stabilizing | 1.0 | D | 0.726 | prob.delet. | None | None | None | None | N |
| R/K | 0.4555 | ambiguous | 0.418 | ambiguous | -0.547 | Destabilizing | 0.998 | D | 0.512 | neutral | None | None | None | None | N |
| R/L | 0.8142 | likely_pathogenic | 0.8118 | pathogenic | 0.206 | Stabilizing | 1.0 | D | 0.58 | neutral | N | 0.486952668 | None | None | N |
| R/M | 0.9288 | likely_pathogenic | 0.9273 | pathogenic | -0.179 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | N |
| R/N | 0.9756 | likely_pathogenic | 0.9772 | pathogenic | -0.131 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | N |
| R/P | 0.9526 | likely_pathogenic | 0.9587 | pathogenic | -0.009 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | N | 0.461787652 | None | None | N |
| R/Q | 0.4968 | ambiguous | 0.5034 | ambiguous | -0.277 | Destabilizing | 1.0 | D | 0.692 | prob.neutral | None | None | None | None | N |
| R/S | 0.9724 | likely_pathogenic | 0.9758 | pathogenic | -0.769 | Destabilizing | 1.0 | D | 0.631 | neutral | N | 0.483837792 | None | None | N |
| R/T | 0.9449 | likely_pathogenic | 0.9493 | pathogenic | -0.498 | Destabilizing | 1.0 | D | 0.627 | neutral | None | None | None | None | N |
| R/V | 0.9234 | likely_pathogenic | 0.9285 | pathogenic | -0.009 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | N |
| R/W | 0.7674 | likely_pathogenic | 0.7762 | pathogenic | -0.285 | Destabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | N |
| R/Y | 0.9291 | likely_pathogenic | 0.9253 | pathogenic | 0.049 | Stabilizing | 1.0 | D | 0.711 | prob.delet. | 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.