Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15550 | 46873;46874;46875 | chr2:178619669;178619668;178619667 | chr2:179484396;179484395;179484394 |
| N2AB | 13909 | 41950;41951;41952 | chr2:178619669;178619668;178619667 | chr2:179484396;179484395;179484394 |
| N2A | 12982 | 39169;39170;39171 | chr2:178619669;178619668;178619667 | chr2:179484396;179484395;179484394 |
| N2B | 6485 | 19678;19679;19680 | chr2:178619669;178619668;178619667 | chr2:179484396;179484395;179484394 |
| Novex-1 | 6610 | 20053;20054;20055 | chr2:178619669;178619668;178619667 | chr2:179484396;179484395;179484394 |
| Novex-2 | 6677 | 20254;20255;20256 | chr2:178619669;178619668;178619667 | chr2:179484396;179484395;179484394 |
| 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/I | rs1229831088  |
-0.463 | 0.999 | D | 0.753 | 0.528 | 0.771231716895 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 6.48E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/I | rs1229831088 |
-0.463 | 0.999 | D | 0.753 | 0.528 | 0.771231716895 | gnomAD-4.0.0 | 6.84868E-07 | None | None | None | None | N | None | 2.99742E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/T | None | None | 0.998 | N | 0.638 | 0.504 | 0.623027447215 | gnomAD-4.0.0 | 6.84868E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.00132E-07 | 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 | 0.798 | likely_pathogenic | 0.7458 | pathogenic | -1.504 | Destabilizing | 0.992 | D | 0.517 | neutral | None | None | None | None | N |
| R/C | 0.2842 | likely_benign | 0.2682 | benign | -1.579 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | N |
| R/D | 0.9676 | likely_pathogenic | 0.9631 | pathogenic | -0.62 | Destabilizing | 0.999 | D | 0.675 | prob.neutral | None | None | None | None | N |
| R/E | 0.802 | likely_pathogenic | 0.7795 | pathogenic | -0.449 | Destabilizing | 0.992 | D | 0.46 | neutral | None | None | None | None | N |
| R/F | 0.8238 | likely_pathogenic | 0.8024 | pathogenic | -1.025 | Destabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | N |
| R/G | 0.7771 | likely_pathogenic | 0.7382 | pathogenic | -1.849 | Destabilizing | 0.994 | D | 0.599 | neutral | D | 0.548412043 | None | None | N |
| R/H | 0.1772 | likely_benign | 0.1757 | benign | -1.791 | Destabilizing | 1.0 | D | 0.577 | neutral | None | None | None | None | N |
| R/I | 0.4173 | ambiguous | 0.3475 | ambiguous | -0.536 | Destabilizing | 0.999 | D | 0.753 | deleterious | D | 0.530277867 | None | None | N |
| R/K | 0.1549 | likely_benign | 0.1604 | benign | -1.424 | Destabilizing | 0.543 | D | 0.259 | neutral | N | 0.516626666 | None | None | N |
| R/L | 0.4543 | ambiguous | 0.4057 | ambiguous | -0.536 | Destabilizing | 0.996 | D | 0.599 | neutral | None | None | None | None | N |
| R/M | 0.5705 | likely_pathogenic | 0.5184 | ambiguous | -0.91 | Destabilizing | 1.0 | D | 0.639 | neutral | None | None | None | None | N |
| R/N | 0.8911 | likely_pathogenic | 0.8788 | pathogenic | -1.058 | Destabilizing | 0.999 | D | 0.543 | neutral | None | None | None | None | N |
| R/P | 0.9924 | likely_pathogenic | 0.9913 | pathogenic | -0.842 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | None | None | None | None | N |
| R/Q | 0.2119 | likely_benign | 0.203 | benign | -1.099 | Destabilizing | 0.998 | D | 0.544 | neutral | None | None | None | None | N |
| R/S | 0.8145 | likely_pathogenic | 0.778 | pathogenic | -1.938 | Destabilizing | 0.989 | D | 0.558 | neutral | N | 0.486465938 | None | None | N |
| R/T | 0.4808 | ambiguous | 0.4069 | ambiguous | -1.564 | Destabilizing | 0.998 | D | 0.638 | neutral | N | 0.434909707 | None | None | N |
| R/V | 0.5185 | ambiguous | 0.4588 | ambiguous | -0.842 | Destabilizing | 0.999 | D | 0.723 | prob.delet. | None | None | None | None | N |
| R/W | 0.4352 | ambiguous | 0.445 | ambiguous | -0.552 | Destabilizing | 1.0 | D | 0.671 | neutral | None | None | None | None | N |
| R/Y | 0.6769 | likely_pathogenic | 0.6819 | pathogenic | -0.32 | Destabilizing | 1.0 | D | 0.715 | 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.