Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31185 | 93778;93779;93780 | chr2:178548073;178548072;178548071 | chr2:179412800;179412799;179412798 |
| N2AB | 29544 | 88855;88856;88857 | chr2:178548073;178548072;178548071 | chr2:179412800;179412799;179412798 |
| N2A | 28617 | 86074;86075;86076 | chr2:178548073;178548072;178548071 | chr2:179412800;179412799;179412798 |
| N2B | 22120 | 66583;66584;66585 | chr2:178548073;178548072;178548071 | chr2:179412800;179412799;179412798 |
| Novex-1 | 22245 | 66958;66959;66960 | chr2:178548073;178548072;178548071 | chr2:179412800;179412799;179412798 |
| Novex-2 | 22312 | 67159;67160;67161 | chr2:178548073;178548072;178548071 | chr2:179412800;179412799;179412798 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/C | rs768852545  |
-1.415 | 1.0 | N | 0.803 | 0.587 | 0.534767221616 | gnomAD-2.1.1 | 1.43E-05 | None | None | None | None | N | None | 8.27E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.56E-05 | 0 |
| R/C | rs768852545 |
-1.415 | 1.0 | N | 0.803 | 0.587 | 0.534767221616 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/C | rs768852545 |
-1.415 | 1.0 | N | 0.803 | 0.587 | 0.534767221616 | gnomAD-4.0.0 | 1.11549E-05 | None | None | None | None | N | None | 8.01539E-05 | 0 | None | 0 | 0 | None | 0 | 1.64366E-04 | 5.08562E-06 | 0 | 8.00512E-05 |
| R/H | rs771533925 |
-1.899 | 1.0 | D | 0.823 | 0.611 | 0.547935346631 | gnomAD-2.1.1 | 2.81E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.57E-05 | None | 1.30727E-04 | None | 0 | 1.77E-05 | 0 |
| R/H | rs771533925 |
-1.899 | 1.0 | D | 0.823 | 0.611 | 0.547935346631 | gnomAD-3.1.2 | 3.94E-05 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 5.76037E-04 | 1.92901E-04 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/H | rs771533925 |
-1.899 | 1.0 | D | 0.823 | 0.611 | 0.547935346631 | gnomAD-4.0.0 | 2.16889E-05 | None | None | None | None | N | None | 2.67115E-05 | 0 | None | 1.01331E-04 | 4.45633E-05 | None | 0 | 0 | 1.4409E-05 | 1.09786E-04 | 1.60092E-05 |
| R/L | rs771533925 |
-0.452 | 1.0 | N | 0.731 | 0.614 | 0.524114710501 | 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 |
| R/L | rs771533925 |
-0.452 | 1.0 | N | 0.731 | 0.614 | 0.524114710501 | gnomAD-4.0.0 | 6.84174E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.51915E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.905 | likely_pathogenic | 0.8798 | pathogenic | -1.864 | Destabilizing | 0.999 | D | 0.636 | neutral | None | None | None | None | N |
| R/C | 0.4464 | ambiguous | 0.3395 | benign | -1.778 | Destabilizing | 1.0 | D | 0.803 | deleterious | N | 0.520991651 | None | None | N |
| R/D | 0.9948 | likely_pathogenic | 0.9926 | pathogenic | -1.176 | Destabilizing | 1.0 | D | 0.77 | deleterious | None | None | None | None | N |
| R/E | 0.913 | likely_pathogenic | 0.8897 | pathogenic | -0.966 | Destabilizing | 0.999 | D | 0.685 | prob.neutral | None | None | None | None | N |
| R/F | 0.9596 | likely_pathogenic | 0.9308 | pathogenic | -0.912 | Destabilizing | 1.0 | D | 0.83 | deleterious | None | None | None | None | N |
| R/G | 0.9278 | likely_pathogenic | 0.8851 | pathogenic | -2.172 | Highly Destabilizing | 1.0 | D | 0.731 | prob.delet. | D | 0.543450772 | None | None | N |
| R/H | 0.4109 | ambiguous | 0.2892 | benign | -2.114 | Highly Destabilizing | 1.0 | D | 0.823 | deleterious | D | 0.532347956 | None | None | N |
| R/I | 0.8484 | likely_pathogenic | 0.8157 | pathogenic | -0.962 | Destabilizing | 1.0 | D | 0.811 | deleterious | None | None | None | None | N |
| R/K | 0.4174 | ambiguous | 0.4176 | ambiguous | -1.35 | Destabilizing | 0.998 | D | 0.651 | neutral | None | None | None | None | N |
| R/L | 0.8058 | likely_pathogenic | 0.729 | pathogenic | -0.962 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | N | 0.507660335 | None | None | N |
| R/M | 0.8613 | likely_pathogenic | 0.8148 | pathogenic | -1.526 | Destabilizing | 1.0 | D | 0.813 | deleterious | None | None | None | None | N |
| R/N | 0.977 | likely_pathogenic | 0.9706 | pathogenic | -1.462 | Destabilizing | 1.0 | D | 0.778 | deleterious | None | None | None | None | N |
| R/P | 0.9986 | likely_pathogenic | 0.9979 | pathogenic | -1.255 | Destabilizing | 1.0 | D | 0.787 | deleterious | D | 0.543957751 | None | None | N |
| R/Q | 0.2513 | likely_benign | 0.2045 | benign | -1.167 | Destabilizing | 1.0 | D | 0.778 | deleterious | None | None | None | None | N |
| R/S | 0.9406 | likely_pathogenic | 0.9198 | pathogenic | -2.128 | Highly Destabilizing | 1.0 | D | 0.741 | deleterious | N | 0.498021869 | None | None | N |
| R/T | 0.887 | likely_pathogenic | 0.8625 | pathogenic | -1.732 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | N |
| R/V | 0.8698 | likely_pathogenic | 0.8429 | pathogenic | -1.255 | Destabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | N |
| R/W | 0.7071 | likely_pathogenic | 0.5525 | ambiguous | -0.605 | Destabilizing | 1.0 | D | 0.77 | deleterious | None | None | None | None | N |
| R/Y | 0.9205 | likely_pathogenic | 0.8644 | pathogenic | -0.491 | Destabilizing | 1.0 | D | 0.823 | 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.