Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21388 | 64387;64388;64389 | chr2:178586739;178586738;178586737 | chr2:179451466;179451465;179451464 |
| N2AB | 19747 | 59464;59465;59466 | chr2:178586739;178586738;178586737 | chr2:179451466;179451465;179451464 |
| N2A | 18820 | 56683;56684;56685 | chr2:178586739;178586738;178586737 | chr2:179451466;179451465;179451464 |
| N2B | 12323 | 37192;37193;37194 | chr2:178586739;178586738;178586737 | chr2:179451466;179451465;179451464 |
| Novex-1 | 12448 | 37567;37568;37569 | chr2:178586739;178586738;178586737 | chr2:179451466;179451465;179451464 |
| Novex-2 | 12515 | 37768;37769;37770 | chr2:178586739;178586738;178586737 | chr2:179451466;179451465;179451464 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/S | None | None | 1.0 | N | 0.835 | 0.439 | 0.779518707146 | gnomAD-4.0.0 | 1.59276E-06 | None | None | None | None | I | None | 0 | 2.2876E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| L/V | None | None | 0.999 | N | 0.514 | 0.209 | 0.404870348458 | gnomAD-4.0.0 | 6.84484E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15966E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.4932 | ambiguous | 0.3963 | ambiguous | -1.887 | Destabilizing | 0.999 | D | 0.733 | prob.delet. | None | None | None | None | I |
| L/C | 0.7855 | likely_pathogenic | 0.6869 | pathogenic | -0.969 | Destabilizing | 1.0 | D | 0.793 | deleterious | None | None | None | None | I |
| L/D | 0.8374 | likely_pathogenic | 0.7347 | pathogenic | -1.62 | Destabilizing | 1.0 | D | 0.848 | deleterious | None | None | None | None | I |
| L/E | 0.5286 | ambiguous | 0.3776 | ambiguous | -1.576 | Destabilizing | 1.0 | D | 0.861 | deleterious | None | None | None | None | I |
| L/F | 0.3608 | ambiguous | 0.2696 | benign | -1.27 | Destabilizing | 1.0 | D | 0.744 | deleterious | N | 0.499741112 | None | None | I |
| L/G | 0.7264 | likely_pathogenic | 0.644 | pathogenic | -2.249 | Highly Destabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | None | I |
| L/H | 0.4688 | ambiguous | 0.3342 | benign | -1.432 | Destabilizing | 1.0 | D | 0.849 | deleterious | None | None | None | None | I |
| L/I | 0.1873 | likely_benign | 0.1369 | benign | -0.938 | Destabilizing | 0.999 | D | 0.466 | neutral | N | 0.43744186 | None | None | I |
| L/K | 0.4424 | ambiguous | 0.3329 | benign | -1.413 | Destabilizing | 1.0 | D | 0.828 | deleterious | None | None | None | None | I |
| L/M | 0.1771 | likely_benign | 0.138 | benign | -0.642 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | I |
| L/N | 0.4886 | ambiguous | 0.3704 | ambiguous | -1.277 | Destabilizing | 1.0 | D | 0.854 | deleterious | None | None | None | None | I |
| L/P | 0.9245 | likely_pathogenic | 0.8746 | pathogenic | -1.226 | Destabilizing | 1.0 | D | 0.855 | deleterious | None | None | None | None | I |
| L/Q | 0.2638 | likely_benign | 0.1765 | benign | -1.419 | Destabilizing | 1.0 | D | 0.839 | deleterious | None | None | None | None | I |
| L/R | 0.4697 | ambiguous | 0.3593 | ambiguous | -0.777 | Destabilizing | 1.0 | D | 0.85 | deleterious | None | None | None | None | I |
| L/S | 0.5654 | likely_pathogenic | 0.4201 | ambiguous | -1.851 | Destabilizing | 1.0 | D | 0.835 | deleterious | N | 0.405769372 | None | None | I |
| L/T | 0.4617 | ambiguous | 0.3341 | benign | -1.693 | Destabilizing | 1.0 | D | 0.819 | deleterious | None | None | None | None | I |
| L/V | 0.2055 | likely_benign | 0.1524 | benign | -1.226 | Destabilizing | 0.999 | D | 0.514 | neutral | N | 0.426398147 | None | None | I |
| L/W | 0.6317 | likely_pathogenic | 0.5046 | ambiguous | -1.42 | Destabilizing | 1.0 | D | 0.825 | deleterious | None | None | None | None | I |
| L/Y | 0.525 | ambiguous | 0.4076 | ambiguous | -1.199 | Destabilizing | 1.0 | D | 0.844 | deleterious | 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.