Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15108 | 45547;45548;45549 | chr2:178621502;178621501;178621500 | chr2:179486229;179486228;179486227 |
| N2AB | 13467 | 40624;40625;40626 | chr2:178621502;178621501;178621500 | chr2:179486229;179486228;179486227 |
| N2A | 12540 | 37843;37844;37845 | chr2:178621502;178621501;178621500 | chr2:179486229;179486228;179486227 |
| N2B | 6043 | 18352;18353;18354 | chr2:178621502;178621501;178621500 | chr2:179486229;179486228;179486227 |
| Novex-1 | 6168 | 18727;18728;18729 | chr2:178621502;178621501;178621500 | chr2:179486229;179486228;179486227 |
| Novex-2 | 6235 | 18928;18929;18930 | chr2:178621502;178621501;178621500 | chr2:179486229;179486228;179486227 |
| 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/P | rs781435431  |
-0.177 | 0.232 | D | 0.547 | 0.253 | 0.343101102393 | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| R/P | rs781435431 |
-0.177 | 0.232 | D | 0.547 | 0.253 | 0.343101102393 | gnomAD-4.0.0 | 2.46512E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.23983E-05 | 0 | 0 |
| R/Q | rs781435431 |
-0.027 | None | N | 0.181 | 0.061 | 0.115124310173 | gnomAD-2.1.1 | 2.02E-05 | None | None | None | None | N | None | 0 | 2.91E-05 | None | 0 | 0 | None | 6.54E-05 | None | 0 | 8.92E-06 | 1.66778E-04 |
| R/Q | rs781435431 |
-0.027 | None | N | 0.181 | 0.061 | 0.115124310173 | gnomAD-4.0.0 | 2.53359E-05 | None | None | None | None | N | None | 0 | 4.48451E-05 | None | 0 | 0 | None | 0 | 1.73853E-04 | 2.33988E-05 | 2.32013E-05 | 9.95454E-05 |
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 | 0.2516 | likely_benign | 0.2088 | benign | -0.574 | Destabilizing | 0.016 | N | 0.399 | neutral | None | None | None | None | N |
| R/C | 0.157 | likely_benign | 0.1487 | benign | -0.49 | Destabilizing | 0.864 | D | 0.477 | neutral | None | None | None | None | N |
| R/D | 0.5811 | likely_pathogenic | 0.4994 | ambiguous | -0.082 | Destabilizing | 0.072 | N | 0.533 | neutral | None | None | None | None | N |
| R/E | 0.2415 | likely_benign | 0.1946 | benign | -0.002 | Destabilizing | 0.016 | N | 0.439 | neutral | None | None | None | None | N |
| R/F | 0.4141 | ambiguous | 0.3775 | ambiguous | -0.671 | Destabilizing | 0.628 | D | 0.509 | neutral | None | None | None | None | N |
| R/G | 0.1765 | likely_benign | 0.1484 | benign | -0.822 | Destabilizing | 0.03 | N | 0.497 | neutral | N | 0.500441921 | None | None | N |
| R/H | 0.0927 | likely_benign | 0.0904 | benign | -1.205 | Destabilizing | 0.214 | N | 0.552 | neutral | None | None | None | None | N |
| R/I | 0.1936 | likely_benign | 0.1613 | benign | 0.07 | Stabilizing | 0.356 | N | 0.528 | neutral | None | None | None | None | N |
| R/K | 0.089 | likely_benign | 0.081 | benign | -0.588 | Destabilizing | None | N | 0.176 | neutral | None | None | None | None | N |
| R/L | 0.2048 | likely_benign | 0.1726 | benign | 0.07 | Stabilizing | 0.13 | N | 0.527 | neutral | N | 0.485403037 | None | None | N |
| R/M | 0.204 | likely_benign | 0.1801 | benign | -0.141 | Destabilizing | 0.356 | N | 0.545 | neutral | None | None | None | None | N |
| R/N | 0.425 | ambiguous | 0.3503 | ambiguous | -0.042 | Destabilizing | 0.072 | N | 0.511 | neutral | None | None | None | None | N |
| R/P | 0.758 | likely_pathogenic | 0.6488 | pathogenic | -0.124 | Destabilizing | 0.232 | N | 0.547 | neutral | D | 0.528698587 | None | None | N |
| R/Q | 0.0764 | likely_benign | 0.0694 | benign | -0.281 | Destabilizing | None | N | 0.181 | neutral | N | 0.482922858 | None | None | N |
| R/S | 0.2887 | likely_benign | 0.244 | benign | -0.704 | Destabilizing | 0.001 | N | 0.239 | neutral | None | None | None | None | N |
| R/T | 0.1534 | likely_benign | 0.1276 | benign | -0.469 | Destabilizing | 0.038 | N | 0.548 | neutral | None | None | None | None | N |
| R/V | 0.2478 | likely_benign | 0.2158 | benign | -0.124 | Destabilizing | 0.072 | N | 0.542 | neutral | None | None | None | None | N |
| R/W | 0.167 | likely_benign | 0.1525 | benign | -0.462 | Destabilizing | 0.864 | D | 0.49 | neutral | None | None | None | None | N |
| R/Y | 0.318 | likely_benign | 0.2853 | benign | -0.119 | Destabilizing | 0.356 | N | 0.529 | 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.