Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24416 | 73471;73472;73473 | chr2:178572886;178572885;178572884 | chr2:179437613;179437612;179437611 |
| N2AB | 22775 | 68548;68549;68550 | chr2:178572886;178572885;178572884 | chr2:179437613;179437612;179437611 |
| N2A | 21848 | 65767;65768;65769 | chr2:178572886;178572885;178572884 | chr2:179437613;179437612;179437611 |
| N2B | 15351 | 46276;46277;46278 | chr2:178572886;178572885;178572884 | chr2:179437613;179437612;179437611 |
| Novex-1 | 15476 | 46651;46652;46653 | chr2:178572886;178572885;178572884 | chr2:179437613;179437612;179437611 |
| Novex-2 | 15543 | 46852;46853;46854 | chr2:178572886;178572885;178572884 | chr2:179437613;179437612;179437611 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs768476881  |
0.06 | 0.013 | N | 0.283 | 0.228 | 0.362758974969 | gnomAD-2.1.1 | 1.79E-05 | None | None | None | None | N | None | 2.068E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| T/I | rs768476881 |
0.06 | 0.013 | N | 0.283 | 0.228 | 0.362758974969 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 1.20715E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/I | rs768476881 |
0.06 | 0.013 | N | 0.283 | 0.228 | 0.362758974969 | gnomAD-4.0.0 | 1.05378E-05 | None | None | None | None | N | None | 1.73616E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 3.39104E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0689 | likely_benign | 0.0711 | benign | -0.614 | Destabilizing | 0.172 | N | 0.366 | neutral | N | 0.478901473 | None | None | N |
| T/C | 0.2143 | likely_benign | 0.2393 | benign | -0.454 | Destabilizing | 0.991 | D | 0.527 | neutral | None | None | None | None | N |
| T/D | 0.3096 | likely_benign | 0.291 | benign | 0.084 | Stabilizing | 0.571 | D | 0.569 | neutral | None | None | None | None | N |
| T/E | 0.247 | likely_benign | 0.223 | benign | 0.077 | Stabilizing | 0.571 | D | 0.566 | neutral | None | None | None | None | N |
| T/F | 0.1406 | likely_benign | 0.1413 | benign | -0.722 | Destabilizing | 0.905 | D | 0.674 | prob.neutral | None | None | None | None | N |
| T/G | 0.2195 | likely_benign | 0.2186 | benign | -0.855 | Destabilizing | 0.4 | N | 0.607 | neutral | None | None | None | None | N |
| T/H | 0.1779 | likely_benign | 0.1771 | benign | -1.071 | Destabilizing | 0.991 | D | 0.631 | neutral | None | None | None | None | N |
| T/I | 0.0945 | likely_benign | 0.0948 | benign | -0.07 | Destabilizing | 0.013 | N | 0.283 | neutral | N | 0.48042241 | None | None | N |
| T/K | 0.1587 | likely_benign | 0.1462 | benign | -0.621 | Destabilizing | 0.571 | D | 0.557 | neutral | None | None | None | None | N |
| T/L | 0.0674 | likely_benign | 0.067 | benign | -0.07 | Destabilizing | 0.216 | N | 0.463 | neutral | None | None | None | None | N |
| T/M | 0.0732 | likely_benign | 0.0736 | benign | 0.018 | Stabilizing | 0.905 | D | 0.555 | neutral | None | None | None | None | N |
| T/N | 0.0783 | likely_benign | 0.0793 | benign | -0.551 | Destabilizing | 0.501 | D | 0.491 | neutral | N | 0.499000112 | None | None | N |
| T/P | 0.0863 | likely_benign | 0.088 | benign | -0.219 | Destabilizing | 0.877 | D | 0.603 | neutral | N | 0.422944915 | None | None | N |
| T/Q | 0.1732 | likely_benign | 0.1634 | benign | -0.67 | Destabilizing | 0.824 | D | 0.584 | neutral | None | None | None | None | N |
| T/R | 0.1613 | likely_benign | 0.1459 | benign | -0.401 | Destabilizing | 0.824 | D | 0.597 | neutral | None | None | None | None | N |
| T/S | 0.0819 | likely_benign | 0.0853 | benign | -0.825 | Destabilizing | 0.006 | N | 0.141 | neutral | N | 0.430004173 | None | None | N |
| T/V | 0.0886 | likely_benign | 0.0903 | benign | -0.219 | Destabilizing | 0.018 | N | 0.161 | neutral | None | None | None | None | N |
| T/W | 0.4654 | ambiguous | 0.4777 | ambiguous | -0.694 | Destabilizing | 0.991 | D | 0.676 | prob.neutral | None | None | None | None | N |
| T/Y | 0.172 | likely_benign | 0.182 | benign | -0.444 | Destabilizing | 0.966 | D | 0.673 | prob.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.