Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17212 | 51859;51860;51861 | chr2:178609789;178609788;178609787 | chr2:179474516;179474515;179474514 |
| N2AB | 15571 | 46936;46937;46938 | chr2:178609789;178609788;178609787 | chr2:179474516;179474515;179474514 |
| N2A | 14644 | 44155;44156;44157 | chr2:178609789;178609788;178609787 | chr2:179474516;179474515;179474514 |
| N2B | 8147 | 24664;24665;24666 | chr2:178609789;178609788;178609787 | chr2:179474516;179474515;179474514 |
| Novex-1 | 8272 | 25039;25040;25041 | chr2:178609789;178609788;178609787 | chr2:179474516;179474515;179474514 |
| Novex-2 | 8339 | 25240;25241;25242 | chr2:178609789;178609788;178609787 | chr2:179474516;179474515;179474514 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/F | rs1473716049  |
-2.131 | 1.0 | D | 0.836 | 0.742 | 0.848487722327 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.57E-05 | None | 0 | None | 0 | 0 | 0 |
| L/F | rs1473716049 |
-2.131 | 1.0 | D | 0.836 | 0.742 | 0.848487722327 | gnomAD-4.0.0 | 4.77864E-06 | None | None | None | None | N | None | 0 | 4.57373E-05 | None | 0 | 2.77393E-05 | None | 0 | 0 | 0 | 0 | 0 |
| L/V | rs1473716049 |
-1.876 | 0.999 | D | 0.821 | 0.687 | 0.812864289982 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.65508E-04 |
| L/V | rs1473716049 |
-1.876 | 0.999 | D | 0.821 | 0.687 | 0.812864289982 | gnomAD-4.0.0 | 1.59288E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.0281E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.9665 | likely_pathogenic | 0.9577 | pathogenic | -2.734 | Highly Destabilizing | 0.999 | D | 0.797 | deleterious | None | None | None | None | N |
| L/C | 0.9412 | likely_pathogenic | 0.9373 | pathogenic | -1.985 | Destabilizing | 1.0 | D | 0.762 | deleterious | None | None | None | None | N |
| L/D | 0.9992 | likely_pathogenic | 0.9989 | pathogenic | -2.83 | Highly Destabilizing | 1.0 | D | 0.83 | deleterious | None | None | None | None | N |
| L/E | 0.9953 | likely_pathogenic | 0.9934 | pathogenic | -2.695 | Highly Destabilizing | 1.0 | D | 0.825 | deleterious | None | None | None | None | N |
| L/F | 0.8096 | likely_pathogenic | 0.7554 | pathogenic | -1.853 | Destabilizing | 1.0 | D | 0.836 | deleterious | D | 0.636419989 | None | None | N |
| L/G | 0.9916 | likely_pathogenic | 0.9886 | pathogenic | -3.218 | Highly Destabilizing | 1.0 | D | 0.809 | deleterious | None | None | None | None | N |
| L/H | 0.9911 | likely_pathogenic | 0.9879 | pathogenic | -2.465 | Highly Destabilizing | 1.0 | D | 0.779 | deleterious | D | 0.669498093 | None | None | N |
| L/I | 0.4712 | ambiguous | 0.4309 | ambiguous | -1.369 | Destabilizing | 0.999 | D | 0.813 | deleterious | D | 0.622409748 | None | None | N |
| L/K | 0.9906 | likely_pathogenic | 0.9869 | pathogenic | -2.106 | Highly Destabilizing | 1.0 | D | 0.807 | deleterious | None | None | None | None | N |
| L/M | 0.4436 | ambiguous | 0.4155 | ambiguous | -1.112 | Destabilizing | 1.0 | D | 0.819 | deleterious | None | None | None | None | N |
| L/N | 0.9931 | likely_pathogenic | 0.9911 | pathogenic | -2.217 | Highly Destabilizing | 1.0 | D | 0.835 | deleterious | None | None | None | None | N |
| L/P | 0.9949 | likely_pathogenic | 0.9933 | pathogenic | -1.802 | Destabilizing | 1.0 | D | 0.828 | deleterious | D | 0.669498093 | None | None | N |
| L/Q | 0.9807 | likely_pathogenic | 0.9746 | pathogenic | -2.251 | Highly Destabilizing | 1.0 | D | 0.827 | deleterious | None | None | None | None | N |
| L/R | 0.9827 | likely_pathogenic | 0.9767 | pathogenic | -1.544 | Destabilizing | 1.0 | D | 0.822 | deleterious | D | 0.653478732 | None | None | N |
| L/S | 0.9949 | likely_pathogenic | 0.9931 | pathogenic | -2.923 | Highly Destabilizing | 1.0 | D | 0.806 | deleterious | None | None | None | None | N |
| L/T | 0.9683 | likely_pathogenic | 0.9609 | pathogenic | -2.651 | Highly Destabilizing | 1.0 | D | 0.79 | deleterious | None | None | None | None | N |
| L/V | 0.5724 | likely_pathogenic | 0.544 | ambiguous | -1.802 | Destabilizing | 0.999 | D | 0.821 | deleterious | D | 0.590249584 | None | None | N |
| L/W | 0.9694 | likely_pathogenic | 0.9568 | pathogenic | -2.12 | Highly Destabilizing | 1.0 | D | 0.736 | prob.delet. | None | None | None | None | N |
| L/Y | 0.9843 | likely_pathogenic | 0.9767 | pathogenic | -1.911 | Destabilizing | 1.0 | D | 0.799 | 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.