Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2192 | 6799;6800;6801 | chr2:178775137;178775136;178775135 | chr2:179639864;179639863;179639862 |
| N2AB | 2192 | 6799;6800;6801 | chr2:178775137;178775136;178775135 | chr2:179639864;179639863;179639862 |
| N2A | 2192 | 6799;6800;6801 | chr2:178775137;178775136;178775135 | chr2:179639864;179639863;179639862 |
| N2B | 2146 | 6661;6662;6663 | chr2:178775137;178775136;178775135 | chr2:179639864;179639863;179639862 |
| Novex-1 | 2146 | 6661;6662;6663 | chr2:178775137;178775136;178775135 | chr2:179639864;179639863;179639862 |
| Novex-2 | 2146 | 6661;6662;6663 | chr2:178775137;178775136;178775135 | chr2:179639864;179639863;179639862 |
| Novex-3 | 2192 | 6799;6800;6801 | chr2:178775137;178775136;178775135 | chr2:179639864;179639863;179639862 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/E | None | None | 0.995 | N | 0.839 | 0.287 | 0.27855597813 | gnomAD-4.0.0 | 1.20033E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.31251E-06 | 0 | 0 |
| A/T | rs774574739  |
-1.516 | 0.905 | N | 0.69 | 0.217 | 0.132336055621 | gnomAD-2.1.1 | 2.79E-05 | None | None | None | None | N | None | 0 | 2.02511E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| A/T | rs774574739 |
-1.516 | 0.905 | N | 0.69 | 0.217 | 0.132336055621 | gnomAD-3.1.2 | 9.21E-05 | None | None | None | None | N | None | 0 | 9.17551E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/T | rs774574739 |
-1.516 | 0.905 | N | 0.69 | 0.217 | 0.132336055621 | gnomAD-4.0.0 | 2.43371E-05 | None | None | None | None | N | None | 0 | 3.22056E-04 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.7594 | likely_pathogenic | 0.7733 | pathogenic | -0.964 | Destabilizing | 0.999 | D | 0.723 | prob.delet. | None | None | None | None | N |
| A/D | 0.9812 | likely_pathogenic | 0.9837 | pathogenic | -1.114 | Destabilizing | 0.996 | D | 0.833 | deleterious | None | None | None | None | N |
| A/E | 0.9484 | likely_pathogenic | 0.9525 | pathogenic | -1.02 | Destabilizing | 0.995 | D | 0.839 | deleterious | N | 0.486887614 | None | None | N |
| A/F | 0.8705 | likely_pathogenic | 0.8854 | pathogenic | -0.722 | Destabilizing | 0.978 | D | 0.836 | deleterious | None | None | None | None | N |
| A/G | 0.4149 | ambiguous | 0.4277 | ambiguous | -1.287 | Destabilizing | 0.951 | D | 0.691 | prob.neutral | N | 0.392961642 | None | None | N |
| A/H | 0.9768 | likely_pathogenic | 0.9787 | pathogenic | -1.559 | Destabilizing | 0.999 | D | 0.795 | deleterious | None | None | None | None | N |
| A/I | 0.5104 | ambiguous | 0.5241 | ambiguous | 0.12 | Stabilizing | 0.864 | D | 0.727 | prob.delet. | None | None | None | None | N |
| A/K | 0.9769 | likely_pathogenic | 0.9797 | pathogenic | -1.049 | Destabilizing | 0.989 | D | 0.835 | deleterious | None | None | None | None | N |
| A/L | 0.508 | ambiguous | 0.5161 | ambiguous | 0.12 | Stabilizing | 0.724 | D | 0.604 | neutral | None | None | None | None | N |
| A/M | 0.6139 | likely_pathogenic | 0.6219 | pathogenic | -0.031 | Destabilizing | 0.724 | D | 0.551 | neutral | None | None | None | None | N |
| A/N | 0.9526 | likely_pathogenic | 0.9578 | pathogenic | -1.002 | Destabilizing | 0.996 | D | 0.825 | deleterious | None | None | None | None | N |
| A/P | 0.9924 | likely_pathogenic | 0.9927 | pathogenic | -0.169 | Destabilizing | 0.995 | D | 0.839 | deleterious | N | 0.486887614 | None | None | N |
| A/Q | 0.9318 | likely_pathogenic | 0.9373 | pathogenic | -0.941 | Destabilizing | 0.989 | D | 0.84 | deleterious | None | None | None | None | N |
| A/R | 0.9555 | likely_pathogenic | 0.9596 | pathogenic | -1.01 | Destabilizing | 0.989 | D | 0.839 | deleterious | None | None | None | None | N |
| A/S | 0.3487 | ambiguous | 0.3651 | ambiguous | -1.51 | Destabilizing | 0.951 | D | 0.679 | prob.neutral | N | 0.37004279 | None | None | N |
| A/T | 0.2889 | likely_benign | 0.2928 | benign | -1.28 | Destabilizing | 0.905 | D | 0.69 | prob.neutral | N | 0.391477519 | None | None | N |
| A/V | 0.2039 | likely_benign | 0.2076 | benign | -0.169 | Destabilizing | 0.051 | N | 0.311 | neutral | N | 0.347633442 | None | None | N |
| A/W | 0.9926 | likely_pathogenic | 0.9935 | pathogenic | -1.258 | Destabilizing | 0.999 | D | 0.815 | deleterious | None | None | None | None | N |
| A/Y | 0.9592 | likely_pathogenic | 0.9632 | pathogenic | -0.734 | Destabilizing | 0.996 | D | 0.812 | 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.