Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1913 | 5962;5963;5964 | chr2:178776127;178776126;178776125 | chr2:179640854;179640853;179640852 |
| N2AB | 1913 | 5962;5963;5964 | chr2:178776127;178776126;178776125 | chr2:179640854;179640853;179640852 |
| N2A | 1913 | 5962;5963;5964 | chr2:178776127;178776126;178776125 | chr2:179640854;179640853;179640852 |
| N2B | 1867 | 5824;5825;5826 | chr2:178776127;178776126;178776125 | chr2:179640854;179640853;179640852 |
| Novex-1 | 1867 | 5824;5825;5826 | chr2:178776127;178776126;178776125 | chr2:179640854;179640853;179640852 |
| Novex-2 | 1867 | 5824;5825;5826 | chr2:178776127;178776126;178776125 | chr2:179640854;179640853;179640852 |
| Novex-3 | 1913 | 5962;5963;5964 | chr2:178776127;178776126;178776125 | chr2:179640854;179640853;179640852 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | None | None | 0.454 | N | 0.673 | 0.396 | 0.387689773709 | gnomAD-4.0.0 | 1.59052E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85657E-06 | 0 | 0 |
| T/N | rs1306092689  |
-1.318 | 0.934 | N | 0.707 | 0.235 | 0.440810947182 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-05 | 0 |
| T/N | rs1306092689 |
-1.318 | 0.934 | N | 0.707 | 0.235 | 0.440810947182 | 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 |
| T/N | rs1306092689 |
-1.318 | 0.934 | N | 0.707 | 0.235 | 0.440810947182 | gnomAD-4.0.0 | 6.57333E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.46985E-05 | 0 | 0 |
| T/S | rs1306092689 |
None | 0.051 | N | 0.289 | 0.195 | 0.185906805712 | 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 |
| T/S | rs1306092689 |
None | 0.051 | N | 0.289 | 0.195 | 0.185906805712 | gnomAD-4.0.0 | 6.57333E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.46985E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1409 | likely_benign | 0.1564 | benign | -1.186 | Destabilizing | 0.454 | N | 0.474 | neutral | N | 0.500149132 | None | None | N |
| T/C | 0.5768 | likely_pathogenic | 0.5684 | pathogenic | -0.933 | Destabilizing | 0.998 | D | 0.706 | prob.neutral | None | None | None | None | N |
| T/D | 0.8559 | likely_pathogenic | 0.8788 | pathogenic | -1.849 | Destabilizing | 0.842 | D | 0.729 | prob.delet. | None | None | None | None | N |
| T/E | 0.6285 | likely_pathogenic | 0.6879 | pathogenic | -1.628 | Destabilizing | 0.842 | D | 0.717 | prob.delet. | None | None | None | None | N |
| T/F | 0.4604 | ambiguous | 0.5029 | ambiguous | -0.616 | Destabilizing | 0.949 | D | 0.743 | deleterious | None | None | None | None | N |
| T/G | 0.5998 | likely_pathogenic | 0.6063 | pathogenic | -1.603 | Destabilizing | 0.728 | D | 0.709 | prob.delet. | None | None | None | None | N |
| T/H | 0.5271 | ambiguous | 0.5824 | pathogenic | -1.675 | Destabilizing | 0.998 | D | 0.709 | prob.delet. | None | None | None | None | N |
| T/I | 0.1997 | likely_benign | 0.2082 | benign | -0.079 | Destabilizing | 0.454 | N | 0.673 | neutral | N | 0.441845383 | None | None | N |
| T/K | 0.4846 | ambiguous | 0.5543 | ambiguous | -0.781 | Destabilizing | 0.842 | D | 0.707 | prob.neutral | None | None | None | None | N |
| T/L | 0.1647 | likely_benign | 0.1751 | benign | -0.079 | Destabilizing | 0.007 | N | 0.411 | neutral | None | None | None | None | N |
| T/M | 0.1018 | likely_benign | 0.1109 | benign | -0.26 | Destabilizing | 0.949 | D | 0.743 | deleterious | None | None | None | None | N |
| T/N | 0.376 | ambiguous | 0.3845 | ambiguous | -1.499 | Destabilizing | 0.934 | D | 0.707 | prob.neutral | N | 0.495659986 | None | None | N |
| T/P | 0.9602 | likely_pathogenic | 0.9631 | pathogenic | -0.419 | Destabilizing | 0.966 | D | 0.738 | prob.delet. | D | 0.575157868 | None | None | N |
| T/Q | 0.4098 | ambiguous | 0.4544 | ambiguous | -1.175 | Destabilizing | 0.974 | D | 0.74 | deleterious | None | None | None | None | N |
| T/R | 0.4425 | ambiguous | 0.5137 | ambiguous | -1.045 | Destabilizing | 0.949 | D | 0.737 | prob.delet. | None | None | None | None | N |
| T/S | 0.1998 | likely_benign | 0.211 | benign | -1.65 | Destabilizing | 0.051 | N | 0.289 | neutral | N | 0.468777809 | None | None | N |
| T/V | 0.1535 | likely_benign | 0.153 | benign | -0.419 | Destabilizing | 0.029 | N | 0.241 | neutral | None | None | None | None | N |
| T/W | 0.8474 | likely_pathogenic | 0.868 | pathogenic | -0.903 | Destabilizing | 0.998 | D | 0.712 | prob.delet. | None | None | None | None | N |
| T/Y | 0.625 | likely_pathogenic | 0.6581 | pathogenic | -0.515 | Destabilizing | 0.991 | D | 0.751 | 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.