Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22522 | 67789;67790;67791 | chr2:178579633;178579632;178579631 | chr2:179444360;179444359;179444358 |
| N2AB | 20881 | 62866;62867;62868 | chr2:178579633;178579632;178579631 | chr2:179444360;179444359;179444358 |
| N2A | 19954 | 60085;60086;60087 | chr2:178579633;178579632;178579631 | chr2:179444360;179444359;179444358 |
| N2B | 13457 | 40594;40595;40596 | chr2:178579633;178579632;178579631 | chr2:179444360;179444359;179444358 |
| Novex-1 | 13582 | 40969;40970;40971 | chr2:178579633;178579632;178579631 | chr2:179444360;179444359;179444358 |
| Novex-2 | 13649 | 41170;41171;41172 | chr2:178579633;178579632;178579631 | chr2:179444360;179444359;179444358 |
| 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/K | None | None | 0.997 | N | 0.665 | 0.393 | 0.396645960531 | gnomAD-4.0.0 | 4.79053E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.29754E-06 | 0 | 0 |
| R/T | rs1221271318  |
-1.61 | 1.0 | N | 0.749 | 0.441 | 0.76439726516 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/T | rs1221271318 |
-1.61 | 1.0 | N | 0.749 | 0.441 | 0.76439726516 | gnomAD-4.0.0 | 1.36872E-06 | None | None | None | None | N | None | 0 | 2.23664E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15945E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.8633 | likely_pathogenic | 0.8716 | pathogenic | -1.791 | Destabilizing | 0.999 | D | 0.645 | neutral | None | None | None | None | N |
| R/C | 0.293 | likely_benign | 0.3204 | benign | -1.816 | Destabilizing | 1.0 | D | 0.806 | deleterious | None | None | None | None | N |
| R/D | 0.9892 | likely_pathogenic | 0.9899 | pathogenic | -0.946 | Destabilizing | 1.0 | D | 0.79 | deleterious | None | None | None | None | N |
| R/E | 0.8519 | likely_pathogenic | 0.8651 | pathogenic | -0.742 | Destabilizing | 0.999 | D | 0.715 | prob.delet. | None | None | None | None | N |
| R/F | 0.9092 | likely_pathogenic | 0.9178 | pathogenic | -1.111 | Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | N |
| R/G | 0.8412 | likely_pathogenic | 0.8717 | pathogenic | -2.127 | Highly Destabilizing | 1.0 | D | 0.739 | prob.delet. | D | 0.541146594 | None | None | N |
| R/H | 0.2173 | likely_benign | 0.2213 | benign | -2.045 | Highly Destabilizing | 1.0 | D | 0.835 | deleterious | None | None | None | None | N |
| R/I | 0.7345 | likely_pathogenic | 0.7503 | pathogenic | -0.826 | Destabilizing | 1.0 | D | 0.823 | deleterious | N | 0.511686033 | None | None | N |
| R/K | 0.263 | likely_benign | 0.2453 | benign | -1.316 | Destabilizing | 0.997 | D | 0.665 | neutral | N | 0.490793394 | None | None | N |
| R/L | 0.6834 | likely_pathogenic | 0.707 | pathogenic | -0.826 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | N |
| R/M | 0.7401 | likely_pathogenic | 0.7523 | pathogenic | -1.329 | Destabilizing | 1.0 | D | 0.82 | deleterious | None | None | None | None | N |
| R/N | 0.9546 | likely_pathogenic | 0.9565 | pathogenic | -1.246 | Destabilizing | 1.0 | D | 0.799 | deleterious | None | None | None | None | N |
| R/P | 0.9971 | likely_pathogenic | 0.998 | pathogenic | -1.135 | Destabilizing | 1.0 | D | 0.803 | deleterious | None | None | None | None | N |
| R/Q | 0.1904 | likely_benign | 0.1973 | benign | -1.126 | Destabilizing | 1.0 | D | 0.799 | deleterious | None | None | None | None | N |
| R/S | 0.9012 | likely_pathogenic | 0.9111 | pathogenic | -2.088 | Highly Destabilizing | 1.0 | D | 0.754 | deleterious | N | 0.50361773 | None | None | N |
| R/T | 0.7992 | likely_pathogenic | 0.8053 | pathogenic | -1.678 | Destabilizing | 1.0 | D | 0.749 | deleterious | N | 0.499111506 | None | None | N |
| R/V | 0.7929 | likely_pathogenic | 0.791 | pathogenic | -1.135 | Destabilizing | 1.0 | D | 0.792 | deleterious | None | None | None | None | N |
| R/W | 0.5032 | ambiguous | 0.5583 | ambiguous | -0.692 | Destabilizing | 1.0 | D | 0.776 | deleterious | None | None | None | None | N |
| R/Y | 0.8244 | likely_pathogenic | 0.8376 | pathogenic | -0.495 | Destabilizing | 1.0 | D | 0.835 | 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.