Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 6725 | 20398;20399;20400 | chr2:178727192;178727191;178727190 | chr2:179591919;179591918;179591917 |
| N2AB | 6408 | 19447;19448;19449 | chr2:178727192;178727191;178727190 | chr2:179591919;179591918;179591917 |
| N2A | 5481 | 16666;16667;16668 | chr2:178727192;178727191;178727190 | chr2:179591919;179591918;179591917 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/M | rs146627500  |
-1.275 | 0.001 | N | 0.421 | 0.09 | None | gnomAD-2.1.1 | 3.41552E-03 | None | None | None | None | N | None | 1.2409E-04 | 7.64873E-04 | None | 1.06631E-03 | 0 | None | 2.17135E-02 | None | 4E-05 | 1.77866E-03 | 3.09772E-03 |
| I/M | rs146627500 |
-1.275 | 0.001 | N | 0.421 | 0.09 | None | gnomAD-3.1.2 | 1.74876E-03 | None | None | None | None | N | None | 1.68911E-04 | 1.70447E-03 | 0 | 8.65052E-04 | 0 | None | 0 | 0 | 1.6473E-03 | 2.37997E-02 | 1.43267E-03 |
| I/M | rs146627500 |
-1.275 | 0.001 | N | 0.421 | 0.09 | None | 1000 genomes | 5.99042E-03 | None | None | None | None | N | None | 0 | 1.4E-03 | None | None | 0 | 2E-03 | None | None | None | 2.76E-02 | None |
| I/M | rs146627500 |
-1.275 | 0.001 | N | 0.421 | 0.09 | None | gnomAD-4.0.0 | 2.17133E-03 | None | None | None | None | N | None | 2.40032E-04 | 9.50412E-04 | None | 8.4528E-04 | 4.45991E-05 | None | 6.24863E-05 | 4.1295E-03 | 1.08779E-03 | 2.11368E-02 | 2.64186E-03 |
| I/V | rs1241938140 |
None | 0.002 | N | 0.38 | 0.152 | 0.165133752707 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs1241938140 |
None | 0.002 | N | 0.38 | 0.152 | 0.165133752707 | gnomAD-4.0.0 | 6.57367E-06 | None | None | None | None | N | None | 2.41289E-05 | 0 | None | 0 | 0 | None | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.7426 | likely_pathogenic | 0.7976 | pathogenic | -2.734 | Highly Destabilizing | 0.016 | N | 0.609 | neutral | None | None | None | None | N |
| I/C | 0.8146 | likely_pathogenic | 0.8407 | pathogenic | -2.016 | Highly Destabilizing | 0.628 | D | 0.765 | deleterious | None | None | None | None | N |
| I/D | 0.9925 | likely_pathogenic | 0.9958 | pathogenic | -3.569 | Highly Destabilizing | 0.356 | N | 0.801 | deleterious | None | None | None | None | N |
| I/E | 0.9806 | likely_pathogenic | 0.9889 | pathogenic | -3.286 | Highly Destabilizing | 0.356 | N | 0.79 | deleterious | None | None | None | None | N |
| I/F | 0.2064 | likely_benign | 0.2725 | benign | -1.708 | Destabilizing | 0.038 | N | 0.611 | neutral | None | None | None | None | N |
| I/G | 0.9418 | likely_pathogenic | 0.9629 | pathogenic | -3.306 | Highly Destabilizing | 0.136 | N | 0.768 | deleterious | None | None | None | None | N |
| I/H | 0.9306 | likely_pathogenic | 0.9628 | pathogenic | -2.904 | Highly Destabilizing | 0.864 | D | 0.831 | deleterious | None | None | None | None | N |
| I/K | 0.9532 | likely_pathogenic | 0.9743 | pathogenic | -2.206 | Highly Destabilizing | 0.055 | N | 0.763 | deleterious | N | 0.468151283 | None | None | N |
| I/L | 0.0471 | likely_benign | 0.0535 | benign | -1.027 | Destabilizing | None | N | 0.229 | neutral | N | 0.281822496 | None | None | N |
| I/M | 0.0913 | likely_benign | 0.1113 | benign | -1.027 | Destabilizing | 0.001 | N | 0.421 | neutral | N | 0.465444033 | None | None | N |
| I/N | 0.9109 | likely_pathogenic | 0.9469 | pathogenic | -2.784 | Highly Destabilizing | 0.356 | N | 0.817 | deleterious | None | None | None | None | N |
| I/P | 0.9781 | likely_pathogenic | 0.9865 | pathogenic | -1.585 | Destabilizing | 0.628 | D | 0.811 | deleterious | None | None | None | None | N |
| I/Q | 0.9257 | likely_pathogenic | 0.9568 | pathogenic | -2.554 | Highly Destabilizing | 0.356 | N | 0.817 | deleterious | None | None | None | None | N |
| I/R | 0.9193 | likely_pathogenic | 0.9539 | pathogenic | -2.053 | Highly Destabilizing | 0.171 | N | 0.801 | deleterious | N | 0.468151283 | None | None | N |
| I/S | 0.8555 | likely_pathogenic | 0.9046 | pathogenic | -3.372 | Highly Destabilizing | 0.072 | N | 0.73 | prob.delet. | None | None | None | None | N |
| I/T | 0.8294 | likely_pathogenic | 0.8761 | pathogenic | -2.938 | Highly Destabilizing | 0.055 | N | 0.661 | neutral | N | 0.456630393 | None | None | N |
| I/V | 0.1387 | likely_benign | 0.1413 | benign | -1.585 | Destabilizing | 0.002 | N | 0.38 | neutral | N | 0.475063593 | None | None | N |
| I/W | 0.8902 | likely_pathogenic | 0.9336 | pathogenic | -2.194 | Highly Destabilizing | 0.864 | D | 0.825 | deleterious | None | None | None | None | N |
| I/Y | 0.7009 | likely_pathogenic | 0.8133 | pathogenic | -1.912 | Destabilizing | 0.356 | N | 0.755 | deleterious | 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.