Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2291 | 7096;7097;7098 | chr2:178774393;178774392;178774391 | chr2:179639120;179639119;179639118 |
| N2AB | 2291 | 7096;7097;7098 | chr2:178774393;178774392;178774391 | chr2:179639120;179639119;179639118 |
| N2A | 2291 | 7096;7097;7098 | chr2:178774393;178774392;178774391 | chr2:179639120;179639119;179639118 |
| N2B | 2245 | 6958;6959;6960 | chr2:178774393;178774392;178774391 | chr2:179639120;179639119;179639118 |
| Novex-1 | 2245 | 6958;6959;6960 | chr2:178774393;178774392;178774391 | chr2:179639120;179639119;179639118 |
| Novex-2 | 2245 | 6958;6959;6960 | chr2:178774393;178774392;178774391 | chr2:179639120;179639119;179639118 |
| Novex-3 | 2291 | 7096;7097;7098 | chr2:178774393;178774392;178774391 | chr2:179639120;179639119;179639118 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/P | rs1199263112  |
0.055 | 0.667 | D | 0.47 | 0.4 | 0.444202592202 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 4.63E-05 | 0 | 0 |
| S/P | rs1199263112 |
0.055 | 0.667 | D | 0.47 | 0.4 | 0.444202592202 | gnomAD-4.0.0 | 1.59084E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.88359E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1119 | likely_benign | 0.1015 | benign | -0.431 | Destabilizing | 0.055 | N | 0.404 | neutral | D | 0.645897906 | None | None | N |
| S/C | 0.2223 | likely_benign | 0.1941 | benign | -0.356 | Destabilizing | 0.883 | D | 0.505 | neutral | D | 0.689762853 | None | None | N |
| S/D | 0.536 | ambiguous | 0.4889 | ambiguous | 0.261 | Stabilizing | 0.272 | N | 0.382 | neutral | None | None | None | None | N |
| S/E | 0.6141 | likely_pathogenic | 0.5558 | ambiguous | 0.222 | Stabilizing | 0.272 | N | 0.381 | neutral | None | None | None | None | N |
| S/F | 0.1924 | likely_benign | 0.1411 | benign | -0.732 | Destabilizing | 0.002 | N | 0.306 | neutral | D | 0.596803449 | None | None | N |
| S/G | 0.1776 | likely_benign | 0.1741 | benign | -0.632 | Destabilizing | 0.272 | N | 0.357 | neutral | None | None | None | None | N |
| S/H | 0.3846 | ambiguous | 0.3232 | benign | -1.097 | Destabilizing | 0.968 | D | 0.486 | neutral | None | None | None | None | N |
| S/I | 0.1636 | likely_benign | 0.1387 | benign | -0.02 | Destabilizing | 0.396 | N | 0.509 | neutral | None | None | None | None | N |
| S/K | 0.6688 | likely_pathogenic | 0.6095 | pathogenic | -0.52 | Destabilizing | 0.272 | N | 0.38 | neutral | None | None | None | None | N |
| S/L | 0.088 | likely_benign | 0.0824 | benign | -0.02 | Destabilizing | 0.157 | N | 0.439 | neutral | None | None | None | None | N |
| S/M | 0.1884 | likely_benign | 0.1644 | benign | 0.092 | Stabilizing | 0.909 | D | 0.481 | neutral | None | None | None | None | N |
| S/N | 0.1688 | likely_benign | 0.1582 | benign | -0.36 | Destabilizing | 0.272 | N | 0.435 | neutral | None | None | None | None | N |
| S/P | 0.8079 | likely_pathogenic | 0.8051 | pathogenic | -0.124 | Destabilizing | 0.667 | D | 0.47 | neutral | D | 0.688023416 | None | None | N |
| S/Q | 0.5348 | ambiguous | 0.4793 | ambiguous | -0.514 | Destabilizing | 0.726 | D | 0.429 | neutral | None | None | None | None | N |
| S/R | 0.628 | likely_pathogenic | 0.5664 | pathogenic | -0.407 | Destabilizing | 0.567 | D | 0.467 | neutral | None | None | None | None | N |
| S/T | 0.0731 | likely_benign | 0.071 | benign | -0.429 | Destabilizing | None | N | 0.123 | neutral | D | 0.561787885 | None | None | N |
| S/V | 0.1838 | likely_benign | 0.1561 | benign | -0.124 | Destabilizing | 0.157 | N | 0.473 | neutral | None | None | None | None | N |
| S/W | 0.4456 | ambiguous | 0.3643 | ambiguous | -0.729 | Destabilizing | 0.968 | D | 0.631 | neutral | None | None | None | None | N |
| S/Y | 0.1875 | likely_benign | 0.1482 | benign | -0.452 | Destabilizing | 0.331 | N | 0.571 | neutral | D | 0.585472214 | 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.