Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1314 | 4165;4166;4167 | chr2:178779252;178779251;178779250 | chr2:179643979;179643978;179643977 |
| N2AB | 1314 | 4165;4166;4167 | chr2:178779252;178779251;178779250 | chr2:179643979;179643978;179643977 |
| N2A | 1314 | 4165;4166;4167 | chr2:178779252;178779251;178779250 | chr2:179643979;179643978;179643977 |
| N2B | 1268 | 4027;4028;4029 | chr2:178779252;178779251;178779250 | chr2:179643979;179643978;179643977 |
| Novex-1 | 1268 | 4027;4028;4029 | chr2:178779252;178779251;178779250 | chr2:179643979;179643978;179643977 |
| Novex-2 | 1268 | 4027;4028;4029 | chr2:178779252;178779251;178779250 | chr2:179643979;179643978;179643977 |
| Novex-3 | 1314 | 4165;4166;4167 | chr2:178779252;178779251;178779250 | chr2:179643979;179643978;179643977 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/I | rs761039819  |
-0.723 | 0.454 | N | 0.601 | 0.27 | 0.365703291355 | gnomAD-2.1.1 | 4E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.45E-05 | None | 0 | None | 0 | 0 | 0 |
| M/I | rs761039819 |
-0.723 | 0.454 | N | 0.601 | 0.27 | 0.365703291355 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.92456E-04 | None | 0 | 0 | 0 | 0 | 0 |
| M/I | rs761039819 |
-0.723 | 0.454 | N | 0.601 | 0.27 | 0.365703291355 | gnomAD-4.0.0 | 4.06013E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.13302E-04 | None | 0 | 0 | 3.61503E-06 | 0 | 0 |
| M/V | rs764249439 |
-1.176 | 0.022 | N | 0.326 | 0.259 | None | gnomAD-2.1.1 | 2.13E-05 | None | None | None | None | N | None | 2.44519E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| M/V | rs764249439 |
-1.176 | 0.022 | N | 0.326 | 0.259 | None | gnomAD-3.1.2 | 1.05132E-04 | None | None | None | None | N | None | 3.61934E-04 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| M/V | rs764249439 |
-1.176 | 0.022 | N | 0.326 | 0.259 | None | gnomAD-4.0.0 | 1.73515E-05 | None | None | None | None | N | None | 3.33725E-04 | 1.66722E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.20092E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.874 | likely_pathogenic | 0.9012 | pathogenic | -2.137 | Highly Destabilizing | 0.525 | D | 0.573 | neutral | None | None | None | None | N |
| M/C | 0.9567 | likely_pathogenic | 0.9658 | pathogenic | -2.393 | Highly Destabilizing | 0.991 | D | 0.766 | deleterious | None | None | None | None | N |
| M/D | 0.9985 | likely_pathogenic | 0.9987 | pathogenic | -1.956 | Destabilizing | 0.949 | D | 0.816 | deleterious | None | None | None | None | N |
| M/E | 0.9872 | likely_pathogenic | 0.9893 | pathogenic | -1.775 | Destabilizing | 0.842 | D | 0.763 | deleterious | None | None | None | None | N |
| M/F | 0.7564 | likely_pathogenic | 0.7785 | pathogenic | -0.791 | Destabilizing | 0.974 | D | 0.729 | prob.delet. | None | None | None | None | N |
| M/G | 0.9775 | likely_pathogenic | 0.9818 | pathogenic | -2.568 | Highly Destabilizing | 0.842 | D | 0.772 | deleterious | None | None | None | None | N |
| M/H | 0.9901 | likely_pathogenic | 0.9921 | pathogenic | -2.063 | Highly Destabilizing | 0.998 | D | 0.792 | deleterious | None | None | None | None | N |
| M/I | 0.6894 | likely_pathogenic | 0.7362 | pathogenic | -0.923 | Destabilizing | 0.454 | N | 0.601 | neutral | N | 0.352808949 | None | None | N |
| M/K | 0.9613 | likely_pathogenic | 0.9695 | pathogenic | -1.248 | Destabilizing | 0.801 | D | 0.705 | prob.neutral | N | 0.490848369 | None | None | N |
| M/L | 0.3703 | ambiguous | 0.4061 | ambiguous | -0.923 | Destabilizing | 0.267 | N | 0.404 | neutral | N | 0.361960862 | None | None | N |
| M/N | 0.9798 | likely_pathogenic | 0.9826 | pathogenic | -1.501 | Destabilizing | 0.949 | D | 0.795 | deleterious | None | None | None | None | N |
| M/P | 0.9934 | likely_pathogenic | 0.9952 | pathogenic | -1.308 | Destabilizing | 0.974 | D | 0.804 | deleterious | None | None | None | None | N |
| M/Q | 0.9338 | likely_pathogenic | 0.9456 | pathogenic | -1.313 | Destabilizing | 0.974 | D | 0.745 | deleterious | None | None | None | None | N |
| M/R | 0.967 | likely_pathogenic | 0.9742 | pathogenic | -1.247 | Destabilizing | 0.966 | D | 0.785 | deleterious | N | 0.473552143 | None | None | N |
| M/S | 0.9496 | likely_pathogenic | 0.9593 | pathogenic | -2.1 | Highly Destabilizing | 0.525 | D | 0.673 | neutral | None | None | None | None | N |
| M/T | 0.8065 | likely_pathogenic | 0.854 | pathogenic | -1.797 | Destabilizing | 0.022 | N | 0.417 | neutral | N | 0.388969164 | None | None | N |
| M/V | 0.1995 | likely_benign | 0.2437 | benign | -1.308 | Destabilizing | 0.022 | N | 0.326 | neutral | N | 0.205309478 | None | None | N |
| M/W | 0.9897 | likely_pathogenic | 0.992 | pathogenic | -1.035 | Destabilizing | 0.998 | D | 0.753 | deleterious | None | None | None | None | N |
| M/Y | 0.9719 | likely_pathogenic | 0.9756 | pathogenic | -0.99 | Destabilizing | 0.991 | D | 0.794 | deleterious | 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.