Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20380 | 61363;61364;61365 | chr2:178590587;178590586;178590585 | chr2:179455314;179455313;179455312 |
| N2AB | 18739 | 56440;56441;56442 | chr2:178590587;178590586;178590585 | chr2:179455314;179455313;179455312 |
| N2A | 17812 | 53659;53660;53661 | chr2:178590587;178590586;178590585 | chr2:179455314;179455313;179455312 |
| N2B | 11315 | 34168;34169;34170 | chr2:178590587;178590586;178590585 | chr2:179455314;179455313;179455312 |
| Novex-1 | 11440 | 34543;34544;34545 | chr2:178590587;178590586;178590585 | chr2:179455314;179455313;179455312 |
| Novex-2 | 11507 | 34744;34745;34746 | chr2:178590587;178590586;178590585 | chr2:179455314;179455313;179455312 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/M | rs201167216  |
-0.86 | 0.994 | D | 0.627 | 0.161 | None | gnomAD-2.1.1 | 3.58639E-04 | None | None | None | None | N | None | 3.77186E-03 | 1.98875E-04 | None | 0 | 0 | None | 0 | None | 0 | 1.57E-05 | 0 |
| L/M | rs201167216 |
-0.86 | 0.994 | D | 0.627 | 0.161 | None | gnomAD-3.1.2 | 1.02618E-03 | None | None | None | None | N | None | 3.64435E-03 | 2.62467E-04 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| L/M | rs201167216 |
-0.86 | 0.994 | D | 0.627 | 0.161 | None | 1000 genomes | 1.79712E-03 | None | None | None | None | N | None | 6.1E-03 | 0 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| L/M | rs201167216 |
-0.86 | 0.994 | D | 0.627 | 0.161 | None | gnomAD-4.0.0 | 1.86032E-04 | None | None | None | None | N | None | 3.54818E-03 | 1.83664E-04 | None | 0 | 0 | None | 0 | 0 | 6.78387E-06 | 0 | 2.40261E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.8531 | likely_pathogenic | 0.7911 | pathogenic | -1.625 | Destabilizing | 0.931 | D | 0.601 | neutral | None | None | None | None | N |
| L/C | 0.7861 | likely_pathogenic | 0.7132 | pathogenic | -1.144 | Destabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | N |
| L/D | 0.9955 | likely_pathogenic | 0.9899 | pathogenic | -1.162 | Destabilizing | 0.999 | D | 0.776 | deleterious | None | None | None | None | N |
| L/E | 0.9683 | likely_pathogenic | 0.9356 | pathogenic | -1.09 | Destabilizing | 0.999 | D | 0.755 | deleterious | None | None | None | None | N |
| L/F | 0.6244 | likely_pathogenic | 0.532 | ambiguous | -0.897 | Destabilizing | 0.996 | D | 0.599 | neutral | None | None | None | None | N |
| L/G | 0.9735 | likely_pathogenic | 0.954 | pathogenic | -1.999 | Destabilizing | 0.999 | D | 0.753 | deleterious | None | None | None | None | N |
| L/H | 0.9455 | likely_pathogenic | 0.9045 | pathogenic | -1.057 | Destabilizing | 1.0 | D | 0.764 | deleterious | None | None | None | None | N |
| L/I | 0.1298 | likely_benign | 0.1177 | benign | -0.641 | Destabilizing | 0.304 | N | 0.245 | neutral | None | None | None | None | N |
| L/K | 0.9484 | likely_pathogenic | 0.907 | pathogenic | -1.289 | Destabilizing | 0.999 | D | 0.723 | prob.delet. | None | None | None | None | N |
| L/M | 0.2791 | likely_benign | 0.2482 | benign | -0.656 | Destabilizing | 0.994 | D | 0.627 | neutral | D | 0.52223397 | None | None | N |
| L/N | 0.9669 | likely_pathogenic | 0.9413 | pathogenic | -1.301 | Destabilizing | 0.999 | D | 0.773 | deleterious | None | None | None | None | N |
| L/P | 0.8476 | likely_pathogenic | 0.7612 | pathogenic | -0.94 | Destabilizing | 0.998 | D | 0.777 | deleterious | N | 0.503725567 | None | None | N |
| L/Q | 0.8937 | likely_pathogenic | 0.8253 | pathogenic | -1.353 | Destabilizing | 0.998 | D | 0.735 | prob.delet. | N | 0.488298178 | None | None | N |
| L/R | 0.9287 | likely_pathogenic | 0.8763 | pathogenic | -0.772 | Destabilizing | 0.998 | D | 0.735 | prob.delet. | N | 0.477195363 | None | None | N |
| L/S | 0.968 | likely_pathogenic | 0.9439 | pathogenic | -1.929 | Destabilizing | 0.996 | D | 0.701 | prob.neutral | None | None | None | None | N |
| L/T | 0.8744 | likely_pathogenic | 0.8059 | pathogenic | -1.725 | Destabilizing | 0.97 | D | 0.628 | neutral | None | None | None | None | N |
| L/V | 0.1445 | likely_benign | 0.1277 | benign | -0.94 | Destabilizing | 0.122 | N | 0.211 | neutral | N | 0.35551391 | None | None | N |
| L/W | 0.8423 | likely_pathogenic | 0.7452 | pathogenic | -1.017 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | N |
| L/Y | 0.8892 | likely_pathogenic | 0.8205 | pathogenic | -0.785 | Destabilizing | 0.999 | D | 0.707 | 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.