Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29741 | 89446;89447;89448 | chr2:178553784;178553783;178553782 | chr2:179418511;179418510;179418509 |
| N2AB | 28100 | 84523;84524;84525 | chr2:178553784;178553783;178553782 | chr2:179418511;179418510;179418509 |
| N2A | 27173 | 81742;81743;81744 | chr2:178553784;178553783;178553782 | chr2:179418511;179418510;179418509 |
| N2B | 20676 | 62251;62252;62253 | chr2:178553784;178553783;178553782 | chr2:179418511;179418510;179418509 |
| Novex-1 | 20801 | 62626;62627;62628 | chr2:178553784;178553783;178553782 | chr2:179418511;179418510;179418509 |
| Novex-2 | 20868 | 62827;62828;62829 | chr2:178553784;178553783;178553782 | chr2:179418511;179418510;179418509 |
| 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/K | rs994680651  |
None | 0.492 | N | 0.774 | 0.402 | 0.762483548826 | 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/K | rs994680651 |
None | 0.492 | N | 0.774 | 0.402 | 0.762483548826 | gnomAD-4.0.0 | 6.57108E-06 | None | None | None | None | N | None | 2.4122E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs751436345 |
-1.802 | 0.003 | N | 0.159 | 0.104 | None | gnomAD-2.1.1 | 8.41E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.85E-05 | 0 |
| I/V | rs751436345 |
-1.802 | 0.003 | N | 0.159 | 0.104 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/V | rs751436345 |
-1.802 | 0.003 | N | 0.159 | 0.104 | None | gnomAD-4.0.0 | 3.74604E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.11607E-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 | 0.7421 | likely_pathogenic | 0.753 | pathogenic | -2.015 | Highly Destabilizing | 0.207 | N | 0.613 | neutral | None | None | None | None | N |
| I/C | 0.8254 | likely_pathogenic | 0.81 | pathogenic | -1.309 | Destabilizing | 0.932 | D | 0.751 | deleterious | None | None | None | None | N |
| I/D | 0.9819 | likely_pathogenic | 0.98 | pathogenic | -2.021 | Highly Destabilizing | 0.932 | D | 0.799 | deleterious | None | None | None | None | N |
| I/E | 0.9558 | likely_pathogenic | 0.9556 | pathogenic | -1.833 | Destabilizing | 0.818 | D | 0.788 | deleterious | None | None | None | None | N |
| I/F | 0.2626 | likely_benign | 0.2334 | benign | -1.095 | Destabilizing | 0.241 | N | 0.7 | prob.neutral | None | None | None | None | N |
| I/G | 0.9118 | likely_pathogenic | 0.9147 | pathogenic | -2.526 | Highly Destabilizing | 0.563 | D | 0.775 | deleterious | None | None | None | None | N |
| I/H | 0.9334 | likely_pathogenic | 0.9254 | pathogenic | -1.945 | Destabilizing | 0.981 | D | 0.801 | deleterious | None | None | None | None | N |
| I/K | 0.9052 | likely_pathogenic | 0.9026 | pathogenic | -1.505 | Destabilizing | 0.492 | N | 0.774 | deleterious | N | 0.499703827 | None | None | N |
| I/L | 0.0857 | likely_benign | 0.0847 | benign | -0.577 | Destabilizing | None | N | 0.185 | neutral | N | 0.340000166 | None | None | N |
| I/M | 0.1152 | likely_benign | 0.1167 | benign | -0.54 | Destabilizing | 0.627 | D | 0.657 | neutral | N | 0.491198987 | None | None | N |
| I/N | 0.8081 | likely_pathogenic | 0.7963 | pathogenic | -1.73 | Destabilizing | 0.932 | D | 0.803 | deleterious | None | None | None | None | N |
| I/P | 0.6946 | likely_pathogenic | 0.725 | pathogenic | -1.033 | Destabilizing | 0.932 | D | 0.798 | deleterious | None | None | None | None | N |
| I/Q | 0.9062 | likely_pathogenic | 0.9054 | pathogenic | -1.634 | Destabilizing | 0.932 | D | 0.803 | deleterious | None | None | None | None | N |
| I/R | 0.885 | likely_pathogenic | 0.8784 | pathogenic | -1.225 | Destabilizing | 0.773 | D | 0.797 | deleterious | N | 0.499703827 | None | None | N |
| I/S | 0.8449 | likely_pathogenic | 0.8372 | pathogenic | -2.425 | Highly Destabilizing | 0.563 | D | 0.735 | prob.delet. | None | None | None | None | N |
| I/T | 0.7905 | likely_pathogenic | 0.7869 | pathogenic | -2.094 | Highly Destabilizing | 0.324 | N | 0.691 | prob.neutral | N | 0.491545704 | None | None | N |
| I/V | 0.1371 | likely_benign | 0.1324 | benign | -1.033 | Destabilizing | 0.003 | N | 0.159 | neutral | N | 0.402035633 | None | None | N |
| I/W | 0.9026 | likely_pathogenic | 0.8807 | pathogenic | -1.449 | Destabilizing | 0.981 | D | 0.79 | deleterious | None | None | None | None | N |
| I/Y | 0.7455 | likely_pathogenic | 0.7077 | pathogenic | -1.112 | Destabilizing | 0.818 | D | 0.768 | 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.