Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25093 | 75502;75503;75504 | chr2:178570855;178570854;178570853 | chr2:179435582;179435581;179435580 |
| N2AB | 23452 | 70579;70580;70581 | chr2:178570855;178570854;178570853 | chr2:179435582;179435581;179435580 |
| N2A | 22525 | 67798;67799;67800 | chr2:178570855;178570854;178570853 | chr2:179435582;179435581;179435580 |
| N2B | 16028 | 48307;48308;48309 | chr2:178570855;178570854;178570853 | chr2:179435582;179435581;179435580 |
| Novex-1 | 16153 | 48682;48683;48684 | chr2:178570855;178570854;178570853 | chr2:179435582;179435581;179435580 |
| Novex-2 | 16220 | 48883;48884;48885 | chr2:178570855;178570854;178570853 | chr2:179435582;179435581;179435580 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | rs748359400  |
None | 0.919 | N | 0.578 | 0.252 | 0.159798565429 | gnomAD-4.0.0 | 6.84296E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99564E-07 | 0 | 0 |
| P/S | rs748359400 |
-1.324 | 0.414 | N | 0.427 | 0.316 | 0.143124449307 | 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 |
| P/S | rs748359400 |
-1.324 | 0.414 | N | 0.427 | 0.316 | 0.143124449307 | gnomAD-4.0.0 | 1.30016E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.61921E-05 | 1.15939E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.1391 | likely_benign | 0.1349 | benign | -1.362 | Destabilizing | 0.919 | D | 0.578 | neutral | N | 0.48007702 | None | None | N |
| P/C | 0.828 | likely_pathogenic | 0.8105 | pathogenic | -0.914 | Destabilizing | 1.0 | D | 0.862 | deleterious | None | None | None | None | N |
| P/D | 0.9468 | likely_pathogenic | 0.9449 | pathogenic | -0.979 | Destabilizing | 0.991 | D | 0.681 | prob.neutral | None | None | None | None | N |
| P/E | 0.8386 | likely_pathogenic | 0.8387 | pathogenic | -1.039 | Destabilizing | 0.991 | D | 0.685 | prob.neutral | None | None | None | None | N |
| P/F | 0.8568 | likely_pathogenic | 0.8448 | pathogenic | -1.243 | Destabilizing | 0.999 | D | 0.871 | deleterious | None | None | None | None | N |
| P/G | 0.5929 | likely_pathogenic | 0.5675 | pathogenic | -1.601 | Destabilizing | 0.938 | D | 0.697 | prob.neutral | None | None | None | None | N |
| P/H | 0.7004 | likely_pathogenic | 0.6864 | pathogenic | -1.029 | Destabilizing | 0.999 | D | 0.838 | deleterious | N | 0.521035697 | None | None | N |
| P/I | 0.78 | likely_pathogenic | 0.7755 | pathogenic | -0.836 | Destabilizing | 0.995 | D | 0.855 | deleterious | None | None | None | None | N |
| P/K | 0.8541 | likely_pathogenic | 0.8527 | pathogenic | -1.002 | Destabilizing | 0.991 | D | 0.677 | prob.neutral | None | None | None | None | N |
| P/L | 0.5247 | ambiguous | 0.5191 | ambiguous | -0.836 | Destabilizing | 0.988 | D | 0.784 | deleterious | N | 0.518754292 | None | None | N |
| P/M | 0.7728 | likely_pathogenic | 0.7523 | pathogenic | -0.604 | Destabilizing | 1.0 | D | 0.839 | deleterious | None | None | None | None | N |
| P/N | 0.8853 | likely_pathogenic | 0.8777 | pathogenic | -0.72 | Destabilizing | 0.991 | D | 0.769 | deleterious | None | None | None | None | N |
| P/Q | 0.7047 | likely_pathogenic | 0.6933 | pathogenic | -0.992 | Destabilizing | 0.991 | D | 0.785 | deleterious | None | None | None | None | N |
| P/R | 0.7615 | likely_pathogenic | 0.7607 | pathogenic | -0.402 | Destabilizing | 0.988 | D | 0.823 | deleterious | N | 0.497562618 | None | None | N |
| P/S | 0.4416 | ambiguous | 0.4168 | ambiguous | -1.219 | Destabilizing | 0.414 | N | 0.427 | neutral | N | 0.504791093 | None | None | N |
| P/T | 0.4919 | ambiguous | 0.4767 | ambiguous | -1.18 | Destabilizing | 0.976 | D | 0.691 | prob.neutral | N | 0.513691863 | None | None | N |
| P/V | 0.623 | likely_pathogenic | 0.6122 | pathogenic | -0.976 | Destabilizing | 0.991 | D | 0.759 | deleterious | None | None | None | None | N |
| P/W | 0.9376 | likely_pathogenic | 0.929 | pathogenic | -1.3 | Destabilizing | 1.0 | D | 0.837 | deleterious | None | None | None | None | N |
| P/Y | 0.836 | likely_pathogenic | 0.8219 | pathogenic | -1.042 | Destabilizing | 1.0 | D | 0.871 | 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.