Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20580 | 61963;61964;61965 | chr2:178589987;178589986;178589985 | chr2:179454714;179454713;179454712 |
| N2AB | 18939 | 57040;57041;57042 | chr2:178589987;178589986;178589985 | chr2:179454714;179454713;179454712 |
| N2A | 18012 | 54259;54260;54261 | chr2:178589987;178589986;178589985 | chr2:179454714;179454713;179454712 |
| N2B | 11515 | 34768;34769;34770 | chr2:178589987;178589986;178589985 | chr2:179454714;179454713;179454712 |
| Novex-1 | 11640 | 35143;35144;35145 | chr2:178589987;178589986;178589985 | chr2:179454714;179454713;179454712 |
| Novex-2 | 11707 | 35344;35345;35346 | chr2:178589987;178589986;178589985 | chr2:179454714;179454713;179454712 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/H | rs2049862820  |
None | 0.001 | N | 0.085 | 0.121 | 0.165133752707 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| N/H | rs2049862820 |
None | 0.001 | N | 0.085 | 0.121 | 0.165133752707 | gnomAD-4.0.0 | 6.57523E-06 | None | None | None | None | N | None | 2.41255E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| N/S | rs1470758075 |
0.232 | None | N | 0.045 | 0.119 | 0.117506650769 | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.63E-05 | None | 3.27E-05 | None | 0 | 0 | 0 |
| N/S | rs1470758075 |
0.232 | None | N | 0.045 | 0.119 | 0.117506650769 | gnomAD-4.0.0 | 1.36893E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99664E-07 | 1.15964E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.2061 | likely_benign | 0.2348 | benign | -0.294 | Destabilizing | 0.055 | N | 0.307 | neutral | None | None | None | None | N |
| N/C | 0.3329 | likely_benign | 0.3174 | benign | 0.48 | Stabilizing | 0.883 | D | 0.323 | neutral | None | None | None | None | N |
| N/D | 0.1877 | likely_benign | 0.2348 | benign | -0.059 | Destabilizing | 0.081 | N | 0.234 | neutral | N | 0.36069323 | None | None | N |
| N/E | 0.4959 | ambiguous | 0.5458 | ambiguous | -0.106 | Destabilizing | 0.055 | N | 0.2 | neutral | None | None | None | None | N |
| N/F | 0.5607 | ambiguous | 0.5885 | pathogenic | -0.702 | Destabilizing | 0.124 | N | 0.393 | neutral | None | None | None | None | N |
| N/G | 0.2623 | likely_benign | 0.317 | benign | -0.454 | Destabilizing | 0.055 | N | 0.221 | neutral | None | None | None | None | N |
| N/H | 0.1315 | likely_benign | 0.1407 | benign | -0.558 | Destabilizing | 0.001 | N | 0.085 | neutral | N | 0.477867117 | None | None | N |
| N/I | 0.4376 | ambiguous | 0.4297 | ambiguous | 0.042 | Stabilizing | 0.175 | N | 0.428 | neutral | N | 0.483062293 | None | None | N |
| N/K | 0.5213 | ambiguous | 0.5571 | ambiguous | 0.126 | Stabilizing | 0.042 | N | 0.201 | neutral | N | 0.458587923 | None | None | N |
| N/L | 0.3341 | likely_benign | 0.3452 | ambiguous | 0.042 | Stabilizing | 0.055 | N | 0.35 | neutral | None | None | None | None | N |
| N/M | 0.4066 | ambiguous | 0.4366 | ambiguous | 0.504 | Stabilizing | 0.859 | D | 0.333 | neutral | None | None | None | None | N |
| N/P | 0.8728 | likely_pathogenic | 0.855 | pathogenic | -0.044 | Destabilizing | 0.667 | D | 0.388 | neutral | None | None | None | None | N |
| N/Q | 0.4062 | ambiguous | 0.4361 | ambiguous | -0.299 | Destabilizing | 0.22 | N | 0.279 | neutral | None | None | None | None | N |
| N/R | 0.5195 | ambiguous | 0.5242 | ambiguous | 0.205 | Stabilizing | 0.22 | N | 0.189 | neutral | None | None | None | None | N |
| N/S | 0.0853 | likely_benign | 0.095 | benign | -0.015 | Destabilizing | None | N | 0.045 | neutral | N | 0.43538299 | None | None | N |
| N/T | 0.1578 | likely_benign | 0.181 | benign | 0.068 | Stabilizing | 0.042 | N | 0.203 | neutral | N | 0.465956613 | None | None | N |
| N/V | 0.3458 | ambiguous | 0.356 | ambiguous | -0.044 | Destabilizing | 0.22 | N | 0.392 | neutral | None | None | None | None | N |
| N/W | 0.8266 | likely_pathogenic | 0.84 | pathogenic | -0.703 | Destabilizing | 0.667 | D | 0.33 | neutral | None | None | None | None | N |
| N/Y | 0.1638 | likely_benign | 0.1865 | benign | -0.432 | Destabilizing | None | N | 0.114 | neutral | N | 0.426688935 | 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.