Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3909 | 11950;11951;11952 | chr2:178741508;178741507;178741506 | chr2:179606235;179606234;179606233 |
| N2AB | 3592 | 10999;11000;11001 | chr2:178741508;178741507;178741506 | chr2:179606235;179606234;179606233 |
| N2A | None | None | chr2:None | chr2:None |
| N2B | 3546 | 10861;10862;10863 | chr2:178741508;178741507;178741506 | chr2:179606235;179606234;179606233 |
| Novex-1 | 3671 | 11236;11237;11238 | chr2:178741508;178741507;178741506 | chr2:179606235;179606234;179606233 |
| Novex-2 | 3738 | 11437;11438;11439 | chr2:178741508;178741507;178741506 | chr2:179606235;179606234;179606233 |
| 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/L | None | None | 0.003 | N | 0.387 | 0.134 | None | gnomAD-4.0.0 | 3.60097E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.625E-06 | 6.07533E-05 | 0 |
| I/T | rs1452766565  |
-1.955 | 0.081 | D | 0.523 | 0.295 | None | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| I/T | rs1452766565 |
-1.955 | 0.081 | D | 0.523 | 0.295 | None | gnomAD-4.0.0 | 8.21015E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.07932E-05 | 0 | 0 |
| I/V | None | None | None | N | 0.285 | 0.076 | None | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 | 0.815 | likely_pathogenic | 0.7457 | pathogenic | -2.43 | Highly Destabilizing | 0.055 | N | 0.543 | neutral | None | None | None | None | N |
| I/C | 0.8602 | likely_pathogenic | 0.826 | pathogenic | -2.025 | Highly Destabilizing | 0.667 | D | 0.607 | neutral | None | None | None | None | N |
| I/D | 0.962 | likely_pathogenic | 0.9372 | pathogenic | -3.161 | Highly Destabilizing | 0.667 | D | 0.641 | neutral | None | None | None | None | N |
| I/E | 0.9085 | likely_pathogenic | 0.8606 | pathogenic | -3.063 | Highly Destabilizing | 0.364 | N | 0.638 | neutral | None | None | None | None | N |
| I/F | 0.3948 | ambiguous | 0.3353 | benign | -1.566 | Destabilizing | 0.175 | N | 0.488 | neutral | D | 0.619400411 | None | None | N |
| I/G | 0.9147 | likely_pathogenic | 0.8708 | pathogenic | -2.835 | Highly Destabilizing | 0.364 | N | 0.628 | neutral | None | None | None | None | N |
| I/H | 0.9152 | likely_pathogenic | 0.8747 | pathogenic | -2.062 | Highly Destabilizing | 0.958 | D | 0.651 | neutral | None | None | None | None | N |
| I/K | 0.8082 | likely_pathogenic | 0.7333 | pathogenic | -1.89 | Destabilizing | 0.22 | N | 0.633 | neutral | None | None | None | None | N |
| I/L | 0.2315 | likely_benign | 0.2128 | benign | -1.302 | Destabilizing | 0.003 | N | 0.387 | neutral | N | 0.52081098 | None | None | N |
| I/M | 0.1664 | likely_benign | 0.1484 | benign | -1.291 | Destabilizing | 0.008 | N | 0.405 | neutral | D | 0.620411052 | None | None | N |
| I/N | 0.6498 | likely_pathogenic | 0.5517 | ambiguous | -2.056 | Highly Destabilizing | 0.822 | D | 0.657 | neutral | D | 0.621055801 | None | None | N |
| I/P | 0.9508 | likely_pathogenic | 0.9236 | pathogenic | -1.656 | Destabilizing | 0.859 | D | 0.639 | neutral | None | None | None | None | N |
| I/Q | 0.863 | likely_pathogenic | 0.8063 | pathogenic | -2.158 | Highly Destabilizing | 0.667 | D | 0.656 | neutral | None | None | None | None | N |
| I/R | 0.7483 | likely_pathogenic | 0.6537 | pathogenic | -1.328 | Destabilizing | 0.667 | D | 0.659 | neutral | None | None | None | None | N |
| I/S | 0.7765 | likely_pathogenic | 0.6861 | pathogenic | -2.609 | Highly Destabilizing | 0.175 | N | 0.567 | neutral | D | 0.620528145 | None | None | N |
| I/T | 0.7336 | likely_pathogenic | 0.6468 | pathogenic | -2.397 | Highly Destabilizing | 0.081 | N | 0.523 | neutral | D | 0.579033094 | None | None | N |
| I/V | 0.1332 | likely_benign | 0.1174 | benign | -1.656 | Destabilizing | None | N | 0.285 | neutral | N | 0.350329813 | None | None | N |
| I/W | 0.9217 | likely_pathogenic | 0.8983 | pathogenic | -1.829 | Destabilizing | 0.958 | D | 0.647 | neutral | None | None | None | None | N |
| I/Y | 0.7722 | likely_pathogenic | 0.7148 | pathogenic | -1.625 | Destabilizing | 0.667 | D | 0.577 | 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.