Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32456 | 97591;97592;97593 | chr2:178542390;178542389;178542388 | chr2:179407117;179407116;179407115 |
| N2AB | 30815 | 92668;92669;92670 | chr2:178542390;178542389;178542388 | chr2:179407117;179407116;179407115 |
| N2A | 29888 | 89887;89888;89889 | chr2:178542390;178542389;178542388 | chr2:179407117;179407116;179407115 |
| N2B | 23391 | 70396;70397;70398 | chr2:178542390;178542389;178542388 | chr2:179407117;179407116;179407115 |
| Novex-1 | 23516 | 70771;70772;70773 | chr2:178542390;178542389;178542388 | chr2:179407117;179407116;179407115 |
| Novex-2 | 23583 | 70972;70973;70974 | chr2:178542390;178542389;178542388 | chr2:179407117;179407116;179407115 |
| 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/G | None | None | 1.0 | N | 0.645 | 0.286 | 0.470484629704 | gnomAD-4.0.0 | 7.52681E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.89463E-06 | 0 | 0 |
| R/K | rs879169496  |
None | 0.997 | N | 0.523 | 0.346 | None | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 6.33473E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/S | rs771232040 |
-0.118 | 1.0 | N | 0.723 | 0.372 | 0.242825505644 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| R/S | rs771232040 |
-0.118 | 1.0 | N | 0.723 | 0.372 | 0.242825505644 | gnomAD-4.0.0 | 1.36852E-06 | None | None | None | None | N | None | 2.98846E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15934E-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 | 0.8224 | likely_pathogenic | 0.7927 | pathogenic | 0.014 | Stabilizing | 0.999 | D | 0.657 | neutral | None | None | None | None | N |
| R/C | 0.5048 | ambiguous | 0.44 | ambiguous | -0.241 | Destabilizing | 1.0 | D | 0.744 | deleterious | None | None | None | None | N |
| R/D | 0.9195 | likely_pathogenic | 0.9014 | pathogenic | -0.146 | Destabilizing | 1.0 | D | 0.716 | prob.delet. | None | None | None | None | N |
| R/E | 0.8 | likely_pathogenic | 0.7627 | pathogenic | -0.09 | Destabilizing | 0.999 | D | 0.66 | neutral | None | None | None | None | N |
| R/F | 0.8919 | likely_pathogenic | 0.8683 | pathogenic | -0.249 | Destabilizing | 1.0 | D | 0.718 | prob.delet. | None | None | None | None | N |
| R/G | 0.6508 | likely_pathogenic | 0.5694 | pathogenic | -0.159 | Destabilizing | 1.0 | D | 0.645 | neutral | N | 0.51213162 | None | None | N |
| R/H | 0.3052 | likely_benign | 0.2646 | benign | -0.608 | Destabilizing | 1.0 | D | 0.767 | deleterious | None | None | None | None | N |
| R/I | 0.7719 | likely_pathogenic | 0.7519 | pathogenic | 0.426 | Stabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | N |
| R/K | 0.3012 | likely_benign | 0.2711 | benign | -0.109 | Destabilizing | 0.997 | D | 0.523 | neutral | N | 0.466378354 | None | None | N |
| R/L | 0.6897 | likely_pathogenic | 0.644 | pathogenic | 0.426 | Stabilizing | 1.0 | D | 0.645 | neutral | None | None | None | None | N |
| R/M | 0.788 | likely_pathogenic | 0.7598 | pathogenic | -0.026 | Destabilizing | 1.0 | D | 0.757 | deleterious | N | 0.517225307 | None | None | N |
| R/N | 0.8914 | likely_pathogenic | 0.8722 | pathogenic | 0.016 | Stabilizing | 1.0 | D | 0.744 | deleterious | None | None | None | None | N |
| R/P | 0.9439 | likely_pathogenic | 0.9309 | pathogenic | 0.308 | Stabilizing | 1.0 | D | 0.716 | prob.delet. | None | None | None | None | N |
| R/Q | 0.3231 | likely_benign | 0.285 | benign | -0.048 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | N |
| R/S | 0.8507 | likely_pathogenic | 0.8175 | pathogenic | -0.273 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | N | 0.513803701 | None | None | N |
| R/T | 0.7516 | likely_pathogenic | 0.7159 | pathogenic | -0.092 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | N | 0.460752359 | None | None | N |
| R/V | 0.7971 | likely_pathogenic | 0.7757 | pathogenic | 0.308 | Stabilizing | 1.0 | D | 0.734 | prob.delet. | None | None | None | None | N |
| R/W | 0.5703 | likely_pathogenic | 0.4887 | ambiguous | -0.359 | Destabilizing | 1.0 | D | 0.757 | deleterious | D | 0.528581612 | None | None | N |
| R/Y | 0.7736 | likely_pathogenic | 0.7244 | pathogenic | 0.056 | Stabilizing | 1.0 | D | 0.734 | 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.