Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3310 | 10153;10154;10155 | chr2:178764587;178764586;178764585 | chr2:179629314;179629313;179629312 |
| N2AB | 3310 | 10153;10154;10155 | chr2:178764587;178764586;178764585 | chr2:179629314;179629313;179629312 |
| N2A | 3310 | 10153;10154;10155 | chr2:178764587;178764586;178764585 | chr2:179629314;179629313;179629312 |
| N2B | 3264 | 10015;10016;10017 | chr2:178764587;178764586;178764585 | chr2:179629314;179629313;179629312 |
| Novex-1 | 3264 | 10015;10016;10017 | chr2:178764587;178764586;178764585 | chr2:179629314;179629313;179629312 |
| Novex-2 | 3264 | 10015;10016;10017 | chr2:178764587;178764586;178764585 | chr2:179629314;179629313;179629312 |
| Novex-3 | 3310 | 10153;10154;10155 | chr2:178764587;178764586;178764585 | chr2:179629314;179629313;179629312 |
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 | rs1433903188  |
None | 0.988 | D | 0.574 | 0.476 | 0.718529551479 | 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/I | rs1433903188 |
None | 0.988 | D | 0.574 | 0.476 | 0.718529551479 | gnomAD-4.0.0 | 4.337E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.23726E-06 | 1.09786E-05 | 1.60036E-05 |
| T/N | None | -0.427 | 0.061 | D | 0.22 | 0.306 | 0.494366844524 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| T/N | None | -0.427 | 0.061 | D | 0.22 | 0.306 | 0.494366844524 | gnomAD-4.0.0 | 4.337E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.93216E-06 | 0 | 0 |
| T/S | rs1433903188 |
-0.799 | 0.31 | N | 0.251 | 0.316 | 0.288352970974 | gnomAD-2.1.1 | 3.18E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 2.87687E-04 | 0 | 0 |
| T/S | rs1433903188 |
-0.799 | 0.31 | N | 0.251 | 0.316 | 0.288352970974 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 1.88466E-04 | 0 | 0 | 0 | 0 |
| T/S | rs1433903188 |
-0.799 | 0.31 | N | 0.251 | 0.316 | 0.288352970974 | gnomAD-4.0.0 | 1.31413E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.88466E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1629 | likely_benign | 0.1365 | benign | -1.47 | Destabilizing | 0.704 | D | 0.478 | neutral | D | 0.58115893 | None | None | N |
| T/C | 0.6417 | likely_pathogenic | 0.5785 | pathogenic | -0.857 | Destabilizing | 0.999 | D | 0.569 | neutral | None | None | None | None | N |
| T/D | 0.7895 | likely_pathogenic | 0.7295 | pathogenic | -1.112 | Destabilizing | 0.884 | D | 0.52 | neutral | None | None | None | None | N |
| T/E | 0.6134 | likely_pathogenic | 0.5369 | ambiguous | -0.892 | Destabilizing | 0.863 | D | 0.506 | neutral | None | None | None | None | N |
| T/F | 0.4171 | ambiguous | 0.3172 | benign | -1.207 | Destabilizing | 0.991 | D | 0.597 | neutral | None | None | None | None | N |
| T/G | 0.5916 | likely_pathogenic | 0.483 | ambiguous | -1.866 | Destabilizing | 0.863 | D | 0.517 | neutral | None | None | None | None | N |
| T/H | 0.3022 | likely_benign | 0.2383 | benign | -1.731 | Destabilizing | 0.1 | N | 0.525 | neutral | None | None | None | None | N |
| T/I | 0.2556 | likely_benign | 0.2321 | benign | -0.412 | Destabilizing | 0.988 | D | 0.574 | neutral | D | 0.542169322 | None | None | N |
| T/K | 0.3146 | likely_benign | 0.2389 | benign | -0.056 | Destabilizing | 0.17 | N | 0.322 | neutral | None | None | None | None | N |
| T/L | 0.1978 | likely_benign | 0.1665 | benign | -0.412 | Destabilizing | 0.969 | D | 0.531 | neutral | None | None | None | None | N |
| T/M | 0.1539 | likely_benign | 0.1318 | benign | -0.448 | Destabilizing | 0.997 | D | 0.572 | neutral | None | None | None | None | N |
| T/N | 0.2899 | likely_benign | 0.251 | benign | -0.703 | Destabilizing | 0.061 | N | 0.22 | neutral | D | 0.593778743 | None | None | N |
| T/P | 0.9141 | likely_pathogenic | 0.8849 | pathogenic | -0.738 | Destabilizing | 0.988 | D | 0.565 | neutral | D | 0.724769076 | None | None | N |
| T/Q | 0.3336 | likely_benign | 0.2627 | benign | -0.523 | Destabilizing | 0.939 | D | 0.559 | neutral | None | None | None | None | N |
| T/R | 0.1972 | likely_benign | 0.1509 | benign | -0.309 | Destabilizing | 0.884 | D | 0.515 | neutral | None | None | None | None | N |
| T/S | 0.1914 | likely_benign | 0.1488 | benign | -1.096 | Destabilizing | 0.31 | N | 0.251 | neutral | N | 0.505484524 | None | None | N |
| T/V | 0.2283 | likely_benign | 0.2005 | benign | -0.738 | Destabilizing | 0.969 | D | 0.511 | neutral | None | None | None | None | N |
| T/W | 0.8062 | likely_pathogenic | 0.714 | pathogenic | -1.186 | Destabilizing | 0.999 | D | 0.656 | neutral | None | None | None | None | N |
| T/Y | 0.4585 | ambiguous | 0.3817 | ambiguous | -0.848 | Destabilizing | 0.982 | D | 0.603 | neutral | 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.