Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28454 | 85585;85586;85587 | chr2:178560772;178560771;178560770 | chr2:179425499;179425498;179425497 |
| N2AB | 26813 | 80662;80663;80664 | chr2:178560772;178560771;178560770 | chr2:179425499;179425498;179425497 |
| N2A | 25886 | 77881;77882;77883 | chr2:178560772;178560771;178560770 | chr2:179425499;179425498;179425497 |
| N2B | 19389 | 58390;58391;58392 | chr2:178560772;178560771;178560770 | chr2:179425499;179425498;179425497 |
| Novex-1 | 19514 | 58765;58766;58767 | chr2:178560772;178560771;178560770 | chr2:179425499;179425498;179425497 |
| Novex-2 | 19581 | 58966;58967;58968 | chr2:178560772;178560771;178560770 | chr2:179425499;179425498;179425497 |
| 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/L | rs747983822  |
None | 0.968 | D | 0.875 | 0.623 | 0.868265480663 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 4.82E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/L | rs747983822 |
None | 0.968 | D | 0.875 | 0.623 | 0.868265480663 | gnomAD-4.0.0 | 1.31422E-05 | None | None | None | None | N | None | 4.82416E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/Q | rs747983822 |
-2.079 | 0.984 | D | 0.811 | 0.665 | 0.803054873015 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| P/Q | rs747983822 |
-2.079 | 0.984 | D | 0.811 | 0.665 | 0.803054873015 | gnomAD-4.0.0 | 6.57108E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.4699E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.1791 | likely_benign | 0.1742 | benign | -2.233 | Highly Destabilizing | 0.103 | N | 0.646 | neutral | D | 0.551386123 | None | None | N |
| P/C | 0.6005 | likely_pathogenic | 0.6027 | pathogenic | -1.986 | Destabilizing | 0.999 | D | 0.893 | deleterious | None | None | None | None | N |
| P/D | 0.9807 | likely_pathogenic | 0.9845 | pathogenic | -3.005 | Highly Destabilizing | 0.976 | D | 0.835 | deleterious | None | None | None | None | N |
| P/E | 0.947 | likely_pathogenic | 0.9523 | pathogenic | -2.831 | Highly Destabilizing | 0.919 | D | 0.832 | deleterious | None | None | None | None | N |
| P/F | 0.9631 | likely_pathogenic | 0.9553 | pathogenic | -1.343 | Destabilizing | 0.996 | D | 0.905 | deleterious | None | None | None | None | N |
| P/G | 0.8228 | likely_pathogenic | 0.8267 | pathogenic | -2.729 | Highly Destabilizing | 0.851 | D | 0.835 | deleterious | None | None | None | None | N |
| P/H | 0.9182 | likely_pathogenic | 0.9264 | pathogenic | -2.352 | Highly Destabilizing | 0.999 | D | 0.867 | deleterious | None | None | None | None | N |
| P/I | 0.5987 | likely_pathogenic | 0.5639 | ambiguous | -0.863 | Destabilizing | 0.988 | D | 0.895 | deleterious | None | None | None | None | N |
| P/K | 0.9643 | likely_pathogenic | 0.9689 | pathogenic | -1.923 | Destabilizing | 0.919 | D | 0.83 | deleterious | None | None | None | None | N |
| P/L | 0.4649 | ambiguous | 0.4189 | ambiguous | -0.863 | Destabilizing | 0.968 | D | 0.875 | deleterious | D | 0.56872991 | None | None | N |
| P/M | 0.7636 | likely_pathogenic | 0.7305 | pathogenic | -1.008 | Destabilizing | 0.999 | D | 0.868 | deleterious | None | None | None | None | N |
| P/N | 0.9463 | likely_pathogenic | 0.9534 | pathogenic | -2.179 | Highly Destabilizing | 0.976 | D | 0.871 | deleterious | None | None | None | None | N |
| P/Q | 0.8787 | likely_pathogenic | 0.8813 | pathogenic | -2.114 | Highly Destabilizing | 0.984 | D | 0.811 | deleterious | D | 0.570504336 | None | None | N |
| P/R | 0.9137 | likely_pathogenic | 0.922 | pathogenic | -1.61 | Destabilizing | 0.968 | D | 0.868 | deleterious | D | 0.569997357 | None | None | N |
| P/S | 0.461 | ambiguous | 0.4911 | ambiguous | -2.762 | Highly Destabilizing | 0.103 | N | 0.616 | neutral | D | 0.524661041 | None | None | N |
| P/T | 0.4091 | ambiguous | 0.4075 | ambiguous | -2.457 | Highly Destabilizing | 0.811 | D | 0.815 | deleterious | D | 0.569490378 | None | None | N |
| P/V | 0.3436 | ambiguous | 0.3153 | benign | -1.293 | Destabilizing | 0.976 | D | 0.864 | deleterious | None | None | None | None | N |
| P/W | 0.9895 | likely_pathogenic | 0.9894 | pathogenic | -1.805 | Destabilizing | 0.999 | D | 0.857 | deleterious | None | None | None | None | N |
| P/Y | 0.9738 | likely_pathogenic | 0.9728 | pathogenic | -1.483 | Destabilizing | 0.996 | D | 0.904 | 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.