Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14914 | 44965;44966;44967 | chr2:178624540;178624539;178624538 | chr2:179489267;179489266;179489265 |
| N2AB | 13273 | 40042;40043;40044 | chr2:178624540;178624539;178624538 | chr2:179489267;179489266;179489265 |
| N2A | 12346 | 37261;37262;37263 | chr2:178624540;178624539;178624538 | chr2:179489267;179489266;179489265 |
| N2B | 5849 | 17770;17771;17772 | chr2:178624540;178624539;178624538 | chr2:179489267;179489266;179489265 |
| Novex-1 | 5974 | 18145;18146;18147 | chr2:178624540;178624539;178624538 | chr2:179489267;179489266;179489265 |
| Novex-2 | 6041 | 18346;18347;18348 | chr2:178624540;178624539;178624538 | chr2:179489267;179489266;179489265 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/Y | rs773211286  |
-1.242 | 0.89 | D | 0.697 | 0.488 | 0.798853050747 | gnomAD-2.1.1 | 2.82E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 3.367E-04 | None | 0 | None | 0 | 8.92E-06 | 0 |
| C/Y | rs773211286 |
-1.242 | 0.89 | D | 0.697 | 0.488 | 0.798853050747 | gnomAD-4.0.0 | 2.66997E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 9.35099E-04 | None | 0 | 0 | 1.79973E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/A | 0.6464 | likely_pathogenic | 0.6155 | pathogenic | -0.717 | Destabilizing | 0.837 | D | 0.484 | neutral | None | None | None | None | N |
| C/D | 0.9914 | likely_pathogenic | 0.9897 | pathogenic | -1.624 | Destabilizing | 0.993 | D | 0.737 | prob.delet. | None | None | None | None | N |
| C/E | 0.9962 | likely_pathogenic | 0.9957 | pathogenic | -1.504 | Destabilizing | 0.978 | D | 0.744 | deleterious | None | None | None | None | N |
| C/F | 0.8966 | likely_pathogenic | 0.8628 | pathogenic | -0.758 | Destabilizing | 0.89 | D | 0.699 | prob.neutral | D | 0.579227593 | None | None | N |
| C/G | 0.6692 | likely_pathogenic | 0.5964 | pathogenic | -0.967 | Destabilizing | 0.97 | D | 0.697 | prob.neutral | D | 0.682198794 | None | None | N |
| C/H | 0.9883 | likely_pathogenic | 0.9857 | pathogenic | -1.622 | Destabilizing | 0.998 | D | 0.721 | prob.delet. | None | None | None | None | N |
| C/I | 0.7422 | likely_pathogenic | 0.7012 | pathogenic | -0.109 | Destabilizing | 0.978 | D | 0.674 | neutral | None | None | None | None | N |
| C/K | 0.9975 | likely_pathogenic | 0.9972 | pathogenic | -0.563 | Destabilizing | 0.978 | D | 0.739 | prob.delet. | None | None | None | None | N |
| C/L | 0.7457 | likely_pathogenic | 0.7373 | pathogenic | -0.109 | Destabilizing | 0.754 | D | 0.548 | neutral | None | None | None | None | N |
| C/M | 0.9102 | likely_pathogenic | 0.9015 | pathogenic | 0.444 | Stabilizing | 0.998 | D | 0.651 | neutral | None | None | None | None | N |
| C/N | 0.9576 | likely_pathogenic | 0.9475 | pathogenic | -0.947 | Destabilizing | 0.993 | D | 0.75 | deleterious | None | None | None | None | N |
| C/P | 0.9841 | likely_pathogenic | 0.9825 | pathogenic | -0.285 | Destabilizing | 0.993 | D | 0.751 | deleterious | None | None | None | None | N |
| C/Q | 0.9909 | likely_pathogenic | 0.9898 | pathogenic | -0.857 | Destabilizing | 0.993 | D | 0.752 | deleterious | None | None | None | None | N |
| C/R | 0.9798 | likely_pathogenic | 0.9771 | pathogenic | -0.768 | Destabilizing | 0.97 | D | 0.751 | deleterious | D | 0.682198794 | None | None | N |
| C/S | 0.6723 | likely_pathogenic | 0.601 | pathogenic | -1.037 | Destabilizing | 0.97 | D | 0.655 | neutral | N | 0.509603973 | None | None | N |
| C/T | 0.6634 | likely_pathogenic | 0.636 | pathogenic | -0.776 | Destabilizing | 0.978 | D | 0.652 | neutral | None | None | None | None | N |
| C/V | 0.5531 | ambiguous | 0.5118 | ambiguous | -0.285 | Destabilizing | 0.926 | D | 0.629 | neutral | None | None | None | None | N |
| C/W | 0.9882 | likely_pathogenic | 0.9834 | pathogenic | -1.206 | Destabilizing | 0.032 | N | 0.443 | neutral | D | 0.683383697 | None | None | N |
| C/Y | 0.97 | likely_pathogenic | 0.9594 | pathogenic | -0.811 | Destabilizing | 0.89 | D | 0.697 | prob.neutral | D | 0.682198794 | 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.