Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 4702 | 14329;14330;14331 | chr2:178738349;178738348;178738347 | chr2:179603076;179603075;179603074 |
| N2AB | 4385 | 13378;13379;13380 | chr2:178738349;178738348;178738347 | chr2:179603076;179603075;179603074 |
| N2A | 3458 | 10597;10598;10599 | chr2:178738349;178738348;178738347 | chr2:179603076;179603075;179603074 |
| N2B | 4339 | 13240;13241;13242 | chr2:178738349;178738348;178738347 | chr2:179603076;179603075;179603074 |
| Novex-1 | 4464 | 13615;13616;13617 | chr2:178738349;178738348;178738347 | chr2:179603076;179603075;179603074 |
| Novex-2 | 4531 | 13816;13817;13818 | chr2:178738349;178738348;178738347 | chr2:179603076;179603075;179603074 |
| 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/F | rs545434193  |
-1.524 | 0.005 | N | 0.264 | 0.181 | 0.402614778071 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 6.47E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/F | rs545434193 |
-1.524 | 0.005 | N | 0.264 | 0.181 | 0.402614778071 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/F | rs545434193 |
-1.524 | 0.005 | N | 0.264 | 0.181 | 0.402614778071 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| I/F | rs545434193 |
-1.524 | 0.005 | N | 0.264 | 0.181 | 0.402614778071 | gnomAD-4.0.0 | 6.56702E-06 | None | None | None | None | N | None | 2.40593E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/M | None | None | 0.934 | N | 0.633 | 0.275 | 0.625177984591 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.625E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.8315 | likely_pathogenic | 0.8053 | pathogenic | -2.123 | Highly Destabilizing | 0.688 | D | 0.623 | neutral | None | None | None | None | N |
| I/C | 0.9168 | likely_pathogenic | 0.8937 | pathogenic | -1.173 | Destabilizing | 0.998 | D | 0.744 | deleterious | None | None | None | None | N |
| I/D | 0.9835 | likely_pathogenic | 0.9718 | pathogenic | -2.132 | Highly Destabilizing | 0.991 | D | 0.829 | deleterious | None | None | None | None | N |
| I/E | 0.9444 | likely_pathogenic | 0.9171 | pathogenic | -2.071 | Highly Destabilizing | 0.991 | D | 0.817 | deleterious | None | None | None | None | N |
| I/F | 0.1287 | likely_benign | 0.1348 | benign | -1.397 | Destabilizing | 0.005 | N | 0.264 | neutral | N | 0.393492211 | None | None | N |
| I/G | 0.9569 | likely_pathogenic | 0.9406 | pathogenic | -2.503 | Highly Destabilizing | 0.991 | D | 0.809 | deleterious | None | None | None | None | N |
| I/H | 0.9177 | likely_pathogenic | 0.877 | pathogenic | -1.834 | Destabilizing | 0.998 | D | 0.835 | deleterious | None | None | None | None | N |
| I/K | 0.8855 | likely_pathogenic | 0.8322 | pathogenic | -1.711 | Destabilizing | 0.974 | D | 0.805 | deleterious | None | None | None | None | N |
| I/L | 0.1163 | likely_benign | 0.099 | benign | -1.098 | Destabilizing | 0.002 | N | 0.218 | neutral | N | 0.469840823 | None | None | N |
| I/M | 0.1248 | likely_benign | 0.1122 | benign | -0.776 | Destabilizing | 0.934 | D | 0.633 | neutral | N | 0.518848708 | None | None | N |
| I/N | 0.8561 | likely_pathogenic | 0.7851 | pathogenic | -1.605 | Destabilizing | 0.989 | D | 0.837 | deleterious | D | 0.65871775 | None | None | N |
| I/P | 0.8469 | likely_pathogenic | 0.8231 | pathogenic | -1.414 | Destabilizing | 0.991 | D | 0.834 | deleterious | None | None | None | None | N |
| I/Q | 0.8867 | likely_pathogenic | 0.8415 | pathogenic | -1.733 | Destabilizing | 0.991 | D | 0.835 | deleterious | None | None | None | None | N |
| I/R | 0.8334 | likely_pathogenic | 0.7615 | pathogenic | -1.085 | Destabilizing | 0.974 | D | 0.835 | deleterious | None | None | None | None | N |
| I/S | 0.8701 | likely_pathogenic | 0.8221 | pathogenic | -2.162 | Highly Destabilizing | 0.891 | D | 0.771 | deleterious | D | 0.657896749 | None | None | N |
| I/T | 0.838 | likely_pathogenic | 0.7931 | pathogenic | -1.998 | Destabilizing | 0.891 | D | 0.685 | prob.neutral | D | 0.657426794 | None | None | N |
| I/V | 0.1608 | likely_benign | 0.1637 | benign | -1.414 | Destabilizing | 0.267 | N | 0.465 | neutral | N | 0.516753199 | None | None | N |
| I/W | 0.81 | likely_pathogenic | 0.7524 | pathogenic | -1.625 | Destabilizing | 0.998 | D | 0.833 | deleterious | None | None | None | None | N |
| I/Y | 0.6873 | likely_pathogenic | 0.6163 | pathogenic | -1.406 | Destabilizing | 0.728 | D | 0.717 | prob.delet. | 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.