Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32491 | 97696;97697;97698 | chr2:178542285;178542284;178542283 | chr2:179407012;179407011;179407010 |
| N2AB | 30850 | 92773;92774;92775 | chr2:178542285;178542284;178542283 | chr2:179407012;179407011;179407010 |
| N2A | 29923 | 89992;89993;89994 | chr2:178542285;178542284;178542283 | chr2:179407012;179407011;179407010 |
| N2B | 23426 | 70501;70502;70503 | chr2:178542285;178542284;178542283 | chr2:179407012;179407011;179407010 |
| Novex-1 | 23551 | 70876;70877;70878 | chr2:178542285;178542284;178542283 | chr2:179407012;179407011;179407010 |
| Novex-2 | 23618 | 71077;71078;71079 | chr2:178542285;178542284;178542283 | chr2:179407012;179407011;179407010 |
| 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/K | None | None | 0.895 | N | 0.687 | 0.434 | 0.728806067291 | gnomAD-4.0.0 | 6.8563E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.00612E-07 | 0 | 0 |
| I/L | rs1178554764  |
None | 0.098 | N | 0.294 | 0.045 | 0.281780670237 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/L | rs1178554764 |
None | 0.098 | N | 0.294 | 0.045 | 0.281780670237 | gnomAD-4.0.0 | 6.57272E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47029E-05 | 0 | 0 |
| I/T | rs781572378 |
-0.351 | 0.546 | N | 0.491 | 0.303 | 0.462982567029 | gnomAD-2.1.1 | 3.27E-05 | None | None | None | None | I | None | 4.23E-05 | 1.43308E-04 | None | 0 | 0 | None | 6.69E-05 | None | 0 | 7.97E-06 | 0 |
| I/T | rs781572378 |
-0.351 | 0.546 | N | 0.491 | 0.303 | 0.462982567029 | gnomAD-3.1.2 | 4.6E-05 | None | None | None | None | I | None | 9.65E-05 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| I/T | rs781572378 |
-0.351 | 0.546 | N | 0.491 | 0.303 | 0.462982567029 | gnomAD-4.0.0 | 2.29723E-05 | None | None | None | None | I | None | 5.34402E-05 | 1.17296E-04 | None | 0 | 0 | None | 0 | 0 | 1.86699E-05 | 2.21004E-05 | 3.20832E-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 | 0.2248 | likely_benign | 0.1722 | benign | -2.22 | Highly Destabilizing | 0.248 | N | 0.504 | neutral | None | None | None | None | I |
| I/C | 0.6253 | likely_pathogenic | 0.5625 | ambiguous | -1.417 | Destabilizing | 0.977 | D | 0.557 | neutral | None | None | None | None | I |
| I/D | 0.8689 | likely_pathogenic | 0.7895 | pathogenic | -2.701 | Highly Destabilizing | 0.972 | D | 0.732 | deleterious | None | None | None | None | I |
| I/E | 0.6284 | likely_pathogenic | 0.5362 | ambiguous | -2.43 | Highly Destabilizing | 0.919 | D | 0.685 | prob.delet. | None | None | None | None | I |
| I/F | 0.1954 | likely_benign | 0.1626 | benign | -1.311 | Destabilizing | 0.848 | D | 0.541 | neutral | None | None | None | None | I |
| I/G | 0.751 | likely_pathogenic | 0.6445 | pathogenic | -2.786 | Highly Destabilizing | 0.919 | D | 0.622 | neutral | None | None | None | None | I |
| I/H | 0.5781 | likely_pathogenic | 0.4876 | ambiguous | -2.301 | Highly Destabilizing | 0.992 | D | 0.71 | prob.delet. | None | None | None | None | I |
| I/K | 0.4411 | ambiguous | 0.3367 | benign | -1.751 | Destabilizing | 0.895 | D | 0.687 | prob.delet. | N | 0.468022698 | None | None | I |
| I/L | 0.1427 | likely_benign | 0.1219 | benign | -0.571 | Destabilizing | 0.098 | N | 0.294 | neutral | N | 0.462651657 | None | None | I |
| I/M | 0.0997 | likely_benign | 0.0865 | benign | -0.508 | Destabilizing | 0.808 | D | 0.599 | neutral | N | 0.478103899 | None | None | I |
| I/N | 0.5208 | ambiguous | 0.4322 | ambiguous | -2.278 | Highly Destabilizing | 0.972 | D | 0.715 | prob.delet. | None | None | None | None | I |
| I/P | 0.949 | likely_pathogenic | 0.9071 | pathogenic | -1.104 | Destabilizing | 0.972 | D | 0.726 | deleterious | None | None | None | None | I |
| I/Q | 0.469 | ambiguous | 0.366 | ambiguous | -2.043 | Highly Destabilizing | 0.972 | D | 0.727 | deleterious | None | None | None | None | I |
| I/R | 0.3551 | ambiguous | 0.2509 | benign | -1.652 | Destabilizing | 0.895 | D | 0.721 | deleterious | N | 0.468022698 | None | None | I |
| I/S | 0.3382 | likely_benign | 0.2702 | benign | -2.915 | Highly Destabilizing | 0.848 | D | 0.641 | neutral | None | None | None | None | I |
| I/T | 0.0957 | likely_benign | 0.0808 | benign | -2.483 | Highly Destabilizing | 0.546 | D | 0.491 | neutral | N | 0.489358255 | None | None | I |
| I/V | 0.062 | likely_benign | 0.0596 | benign | -1.104 | Destabilizing | 0.001 | N | 0.141 | neutral | N | 0.370778859 | None | None | I |
| I/W | 0.785 | likely_pathogenic | 0.7181 | pathogenic | -1.728 | Destabilizing | 0.992 | D | 0.776 | deleterious | None | None | None | None | I |
| I/Y | 0.6022 | likely_pathogenic | 0.5455 | ambiguous | -1.367 | Destabilizing | 0.919 | D | 0.613 | neutral | None | None | None | None | I |
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.