Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28209 | 84850;84851;84852 | chr2:178561507;178561506;178561505 | chr2:179426234;179426233;179426232 |
| N2AB | 26568 | 79927;79928;79929 | chr2:178561507;178561506;178561505 | chr2:179426234;179426233;179426232 |
| N2A | 25641 | 77146;77147;77148 | chr2:178561507;178561506;178561505 | chr2:179426234;179426233;179426232 |
| N2B | 19144 | 57655;57656;57657 | chr2:178561507;178561506;178561505 | chr2:179426234;179426233;179426232 |
| Novex-1 | 19269 | 58030;58031;58032 | chr2:178561507;178561506;178561505 | chr2:179426234;179426233;179426232 |
| Novex-2 | 19336 | 58231;58232;58233 | chr2:178561507;178561506;178561505 | chr2:179426234;179426233;179426232 |
| 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/L | rs753472730  |
-0.946 | 0.061 | N | 0.201 | 0.111 | 0.365703291355 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/L | rs753472730 |
-0.946 | 0.061 | N | 0.201 | 0.111 | 0.365703291355 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/L | rs753472730 |
-0.946 | 0.061 | N | 0.201 | 0.111 | 0.365703291355 | gnomAD-4.0.0 | 1.23956E-06 | None | None | None | None | N | None | 0 | 3.33444E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs1703653060 |
None | 0.99 | N | 0.631 | 0.389 | 0.645699082809 | gnomAD-4.0.0 | 1.36862E-06 | None | None | None | None | N | None | 0 | 0 | None | 3.8276E-05 | 0 | None | 0 | 0 | 0 | 1.15953E-05 | 0 |
| I/V | rs753472730 |
-1.451 | 0.817 | N | 0.367 | 0.078 | 0.48505662038 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.59E-05 | None | 3.27E-05 | None | 0 | 0 | 0 |
| I/V | rs753472730 |
-1.451 | 0.817 | N | 0.367 | 0.078 | 0.48505662038 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.92976E-04 | None | 0 | 0 | 0 | 2.07211E-04 | 0 |
| I/V | rs753472730 |
-1.451 | 0.817 | N | 0.367 | 0.078 | 0.48505662038 | gnomAD-4.0.0 | 5.57801E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 6.69254E-05 | None | 0 | 0 | 0 | 3.29431E-05 | 4.804E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.6527 | likely_pathogenic | 0.6475 | pathogenic | -2.619 | Highly Destabilizing | 0.993 | D | 0.517 | neutral | None | None | None | None | N |
| I/C | 0.8672 | likely_pathogenic | 0.8669 | pathogenic | -1.6 | Destabilizing | 1.0 | D | 0.672 | neutral | None | None | None | None | N |
| I/D | 0.9875 | likely_pathogenic | 0.9891 | pathogenic | -3.053 | Highly Destabilizing | 0.999 | D | 0.783 | deleterious | None | None | None | None | N |
| I/E | 0.9677 | likely_pathogenic | 0.9701 | pathogenic | -2.852 | Highly Destabilizing | 0.999 | D | 0.773 | deleterious | None | None | None | None | N |
| I/F | 0.5879 | likely_pathogenic | 0.5596 | ambiguous | -1.62 | Destabilizing | 0.994 | D | 0.6 | neutral | N | 0.490914617 | None | None | N |
| I/G | 0.9544 | likely_pathogenic | 0.9556 | pathogenic | -3.13 | Highly Destabilizing | 0.999 | D | 0.757 | deleterious | None | None | None | None | N |
| I/H | 0.9446 | likely_pathogenic | 0.9478 | pathogenic | -2.606 | Highly Destabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | N |
| I/K | 0.932 | likely_pathogenic | 0.9404 | pathogenic | -2.028 | Highly Destabilizing | 0.999 | D | 0.757 | deleterious | None | None | None | None | N |
| I/L | 0.1646 | likely_benign | 0.1524 | benign | -1.138 | Destabilizing | 0.061 | N | 0.201 | neutral | N | 0.513977059 | None | None | N |
| I/M | 0.2259 | likely_benign | 0.2022 | benign | -0.855 | Destabilizing | 0.994 | D | 0.607 | neutral | N | 0.499815387 | None | None | N |
| I/N | 0.8495 | likely_pathogenic | 0.8468 | pathogenic | -2.282 | Highly Destabilizing | 0.999 | D | 0.783 | deleterious | N | 0.482672183 | None | None | N |
| I/P | 0.937 | likely_pathogenic | 0.9495 | pathogenic | -1.615 | Destabilizing | 0.999 | D | 0.783 | deleterious | None | None | None | None | N |
| I/Q | 0.9112 | likely_pathogenic | 0.9168 | pathogenic | -2.2 | Highly Destabilizing | 0.999 | D | 0.773 | deleterious | None | None | None | None | N |
| I/R | 0.8925 | likely_pathogenic | 0.9054 | pathogenic | -1.649 | Destabilizing | 0.999 | D | 0.786 | deleterious | None | None | None | None | N |
| I/S | 0.7768 | likely_pathogenic | 0.7723 | pathogenic | -2.906 | Highly Destabilizing | 0.999 | D | 0.667 | neutral | N | 0.463474611 | None | None | N |
| I/T | 0.5186 | ambiguous | 0.5198 | ambiguous | -2.578 | Highly Destabilizing | 0.99 | D | 0.631 | neutral | N | 0.520748316 | None | None | N |
| I/V | 0.1251 | likely_benign | 0.1229 | benign | -1.615 | Destabilizing | 0.817 | D | 0.367 | neutral | N | 0.443519683 | None | None | N |
| I/W | 0.9768 | likely_pathogenic | 0.9777 | pathogenic | -2.077 | Highly Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | N |
| I/Y | 0.9329 | likely_pathogenic | 0.9328 | pathogenic | -1.797 | Destabilizing | 0.999 | D | 0.714 | prob.delet. | 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.