Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2118 | 6577;6578;6579 | chr2:178775512;178775511;178775510 | chr2:179640239;179640238;179640237 |
| N2AB | 2118 | 6577;6578;6579 | chr2:178775512;178775511;178775510 | chr2:179640239;179640238;179640237 |
| N2A | 2118 | 6577;6578;6579 | chr2:178775512;178775511;178775510 | chr2:179640239;179640238;179640237 |
| N2B | 2072 | 6439;6440;6441 | chr2:178775512;178775511;178775510 | chr2:179640239;179640238;179640237 |
| Novex-1 | 2072 | 6439;6440;6441 | chr2:178775512;178775511;178775510 | chr2:179640239;179640238;179640237 |
| Novex-2 | 2072 | 6439;6440;6441 | chr2:178775512;178775511;178775510 | chr2:179640239;179640238;179640237 |
| Novex-3 | 2118 | 6577;6578;6579 | chr2:178775512;178775511;178775510 | chr2:179640239;179640238;179640237 |
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/T | rs56404770  |
-2.742 | 0.92 | D | 0.593 | 0.443 | None | gnomAD-2.1.1 | 1.66425E-03 | None | None | None | None | N | None | 1.71516E-02 | 7.63402E-04 | None | 0 | 0 | None | 6.53E-05 | None | 3.98E-05 | 3.88E-05 | 9.71413E-04 |
| I/T | rs56404770 |
-2.742 | 0.92 | D | 0.593 | 0.443 | None | gnomAD-3.1.2 | 4.92426E-03 | None | None | None | None | N | None | 1.69766E-02 | 2.02959E-03 | 0 | 0 | 0 | None | 0 | 0 | 5.88E-05 | 0 | 5.25813E-03 |
| I/T | rs56404770 |
-2.742 | 0.92 | D | 0.593 | 0.443 | None | 1000 genomes | 4.19329E-03 | None | None | None | None | N | None | 1.59E-02 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| I/T | rs56404770 |
-2.742 | 0.92 | D | 0.593 | 0.443 | None | gnomAD-4.0.0 | 9.27537E-04 | None | None | None | None | N | None | 1.75191E-02 | 1.16686E-03 | None | 0 | 0 | None | 1.56235E-05 | 3.29924E-04 | 1.6102E-05 | 4.39184E-05 | 1.39191E-03 |
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 | 0.6513 | likely_pathogenic | 0.6741 | pathogenic | -2.14 | Highly Destabilizing | 0.863 | D | 0.589 | neutral | None | None | None | None | N |
| I/C | 0.9279 | likely_pathogenic | 0.9426 | pathogenic | -1.221 | Destabilizing | 0.999 | D | 0.614 | neutral | None | None | None | None | N |
| I/D | 0.9939 | likely_pathogenic | 0.9945 | pathogenic | -2.644 | Highly Destabilizing | 0.997 | D | 0.693 | prob.neutral | None | None | None | None | N |
| I/E | 0.9751 | likely_pathogenic | 0.9761 | pathogenic | -2.4 | Highly Destabilizing | 0.997 | D | 0.675 | neutral | None | None | None | None | N |
| I/F | 0.431 | ambiguous | 0.4349 | ambiguous | -1.325 | Destabilizing | 0.976 | D | 0.625 | neutral | D | 0.618537 | None | None | N |
| I/G | 0.956 | likely_pathogenic | 0.9613 | pathogenic | -2.653 | Highly Destabilizing | 0.997 | D | 0.683 | prob.neutral | None | None | None | None | N |
| I/H | 0.9767 | likely_pathogenic | 0.9779 | pathogenic | -2.121 | Highly Destabilizing | 0.999 | D | 0.655 | neutral | None | None | None | None | N |
| I/K | 0.9683 | likely_pathogenic | 0.9673 | pathogenic | -1.695 | Destabilizing | 0.997 | D | 0.677 | prob.neutral | None | None | None | None | N |
| I/L | 0.1075 | likely_benign | 0.117 | benign | -0.65 | Destabilizing | 0.005 | N | 0.159 | neutral | N | 0.477650743 | None | None | N |
| I/M | 0.1123 | likely_benign | 0.1163 | benign | -0.489 | Destabilizing | 0.976 | D | 0.637 | neutral | D | 0.64628726 | None | None | N |
| I/N | 0.9404 | likely_pathogenic | 0.9419 | pathogenic | -2.154 | Highly Destabilizing | 0.996 | D | 0.697 | prob.neutral | D | 0.760978509 | None | None | N |
| I/P | 0.9837 | likely_pathogenic | 0.9855 | pathogenic | -1.13 | Destabilizing | 0.997 | D | 0.696 | prob.neutral | None | None | None | None | N |
| I/Q | 0.9511 | likely_pathogenic | 0.9537 | pathogenic | -1.981 | Destabilizing | 0.997 | D | 0.678 | prob.neutral | None | None | None | None | N |
| I/R | 0.9473 | likely_pathogenic | 0.9448 | pathogenic | -1.513 | Destabilizing | 0.997 | D | 0.699 | prob.neutral | None | None | None | None | N |
| I/S | 0.8743 | likely_pathogenic | 0.8809 | pathogenic | -2.744 | Highly Destabilizing | 0.988 | D | 0.657 | neutral | D | 0.723538059 | None | None | N |
| I/T | 0.5383 | ambiguous | 0.5591 | ambiguous | -2.356 | Highly Destabilizing | 0.92 | D | 0.593 | neutral | D | 0.668156786 | None | None | N |
| I/V | 0.0994 | likely_benign | 0.1074 | benign | -1.13 | Destabilizing | 0.061 | N | 0.185 | neutral | N | 0.512740025 | None | None | N |
| I/W | 0.9591 | likely_pathogenic | 0.9608 | pathogenic | -1.739 | Destabilizing | 0.999 | D | 0.681 | prob.neutral | None | None | None | None | N |
| I/Y | 0.9179 | likely_pathogenic | 0.9112 | pathogenic | -1.369 | Destabilizing | 0.997 | D | 0.677 | 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.