Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2852 | 8779;8780;8781 | chr2:178770147;178770146;178770145 | chr2:179634874;179634873;179634872 |
| N2AB | 2852 | 8779;8780;8781 | chr2:178770147;178770146;178770145 | chr2:179634874;179634873;179634872 |
| N2A | 2852 | 8779;8780;8781 | chr2:178770147;178770146;178770145 | chr2:179634874;179634873;179634872 |
| N2B | 2806 | 8641;8642;8643 | chr2:178770147;178770146;178770145 | chr2:179634874;179634873;179634872 |
| Novex-1 | 2806 | 8641;8642;8643 | chr2:178770147;178770146;178770145 | chr2:179634874;179634873;179634872 |
| Novex-2 | 2806 | 8641;8642;8643 | chr2:178770147;178770146;178770145 | chr2:179634874;179634873;179634872 |
| Novex-3 | 2852 | 8779;8780;8781 | chr2:178770147;178770146;178770145 | chr2:179634874;179634873;179634872 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/I | rs1464875201  |
-0.979 | 0.001 | N | 0.191 | 0.277 | 0.372446077551 | gnomAD-2.1.1 | 7.96E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 8.8E-06 | 0 |
| M/I | rs1464875201 |
-0.979 | 0.001 | N | 0.191 | 0.277 | 0.372446077551 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07383E-04 | 0 |
| M/I | rs1464875201 |
-0.979 | 0.001 | N | 0.191 | 0.277 | 0.372446077551 | gnomAD-4.0.0 | 2.56108E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.68025E-05 | 0 |
| M/K | None | None | 0.351 | N | 0.454 | 0.411 | 0.583209036909 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.21507E-04 | 0 |
| M/V | rs1382675661 |
-1.454 | 0.001 | N | 0.204 | 0.341 | 0.276898752692 | gnomAD-2.1.1 | 3.18E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-05 | 0 |
| M/V | rs1382675661 |
-1.454 | 0.001 | N | 0.204 | 0.341 | 0.276898752692 | 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 |
| M/V | rs1382675661 |
-1.454 | 0.001 | N | 0.204 | 0.341 | 0.276898752692 | gnomAD-4.0.0 | 2.0298E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.40978E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.5554 | ambiguous | 0.5917 | pathogenic | -2.468 | Highly Destabilizing | 0.061 | N | 0.323 | neutral | None | None | None | None | N |
| M/C | 0.7583 | likely_pathogenic | 0.7948 | pathogenic | -2.04 | Highly Destabilizing | 0.94 | D | 0.447 | neutral | None | None | None | None | N |
| M/D | 0.9388 | likely_pathogenic | 0.9404 | pathogenic | -1.603 | Destabilizing | 0.418 | N | 0.514 | neutral | None | None | None | None | N |
| M/E | 0.7169 | likely_pathogenic | 0.6945 | pathogenic | -1.475 | Destabilizing | 0.418 | N | 0.496 | neutral | None | None | None | None | N |
| M/F | 0.3253 | likely_benign | 0.3413 | ambiguous | -1.009 | Destabilizing | 0.264 | N | 0.405 | neutral | None | None | None | None | N |
| M/G | 0.8259 | likely_pathogenic | 0.8429 | pathogenic | -2.882 | Highly Destabilizing | 0.418 | N | 0.469 | neutral | None | None | None | None | N |
| M/H | 0.5253 | ambiguous | 0.5692 | pathogenic | -2.101 | Highly Destabilizing | 0.94 | D | 0.485 | neutral | None | None | None | None | N |
| M/I | 0.2881 | likely_benign | 0.3192 | benign | -1.318 | Destabilizing | 0.001 | N | 0.191 | neutral | N | 0.351293102 | None | None | N |
| M/K | 0.4136 | ambiguous | 0.374 | ambiguous | -1.469 | Destabilizing | 0.351 | N | 0.454 | neutral | N | 0.413284461 | None | None | N |
| M/L | 0.1077 | likely_benign | 0.1185 | benign | -1.318 | Destabilizing | None | N | 0.195 | neutral | N | 0.443980622 | None | None | N |
| M/N | 0.6074 | likely_pathogenic | 0.6635 | pathogenic | -1.484 | Destabilizing | 0.418 | N | 0.53 | neutral | None | None | None | None | N |
| M/P | 0.9912 | likely_pathogenic | 0.9887 | pathogenic | -1.68 | Destabilizing | 0.593 | D | 0.518 | neutral | None | None | None | None | N |
| M/Q | 0.3508 | ambiguous | 0.356 | ambiguous | -1.403 | Destabilizing | 0.593 | D | 0.433 | neutral | None | None | None | None | N |
| M/R | 0.4443 | ambiguous | 0.3881 | ambiguous | -1.15 | Destabilizing | 0.351 | N | 0.488 | neutral | N | 0.425164042 | None | None | N |
| M/S | 0.4767 | ambiguous | 0.5392 | ambiguous | -2.137 | Highly Destabilizing | 0.129 | N | 0.401 | neutral | None | None | None | None | N |
| M/T | 0.2574 | likely_benign | 0.2774 | benign | -1.896 | Destabilizing | 0.003 | N | 0.241 | neutral | N | 0.398857888 | None | None | N |
| M/V | 0.103 | likely_benign | 0.1141 | benign | -1.68 | Destabilizing | 0.001 | N | 0.204 | neutral | N | 0.382366342 | None | None | N |
| M/W | 0.6997 | likely_pathogenic | 0.7062 | pathogenic | -1.093 | Destabilizing | 0.983 | D | 0.455 | neutral | None | None | None | None | N |
| M/Y | 0.6046 | likely_pathogenic | 0.6288 | pathogenic | -1.179 | Destabilizing | 0.593 | D | 0.507 | 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.