Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19396 | 58411;58412;58413 | chr2:178594207;178594206;178594205 | chr2:179458934;179458933;179458932 |
| N2AB | 17755 | 53488;53489;53490 | chr2:178594207;178594206;178594205 | chr2:179458934;179458933;179458932 |
| N2A | 16828 | 50707;50708;50709 | chr2:178594207;178594206;178594205 | chr2:179458934;179458933;179458932 |
| N2B | 10331 | 31216;31217;31218 | chr2:178594207;178594206;178594205 | chr2:179458934;179458933;179458932 |
| Novex-1 | 10456 | 31591;31592;31593 | chr2:178594207;178594206;178594205 | chr2:179458934;179458933;179458932 |
| Novex-2 | 10523 | 31792;31793;31794 | chr2:178594207;178594206;178594205 | chr2:179458934;179458933;179458932 |
| 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/F | rs1277629300  |
-1.239 | 0.638 | D | 0.585 | 0.176 | 0.610090021501 | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | N | None | 0 | 5.82E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| L/F | rs1277629300 |
-1.239 | 0.638 | D | 0.585 | 0.176 | 0.610090021501 | gnomAD-4.0.0 | 1.36879E-06 | None | None | None | None | N | None | 0 | 2.23884E-05 | None | 0 | 0 | None | 0 | 0 | 8.99577E-07 | 0 | 0 |
| L/P | rs1217157718 |
-1.352 | 0.916 | N | 0.72 | 0.603 | 0.878231333192 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| L/P | rs1217157718 |
-1.352 | 0.916 | N | 0.72 | 0.603 | 0.878231333192 | gnomAD-4.0.0 | 2.7376E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 4.63908E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.4319 | ambiguous | 0.4046 | ambiguous | -1.962 | Destabilizing | 0.399 | N | 0.523 | neutral | None | None | None | None | N |
| L/C | 0.5605 | ambiguous | 0.5063 | ambiguous | -1.472 | Destabilizing | 0.982 | D | 0.635 | neutral | None | None | None | None | N |
| L/D | 0.864 | likely_pathogenic | 0.8319 | pathogenic | -1.158 | Destabilizing | 0.826 | D | 0.721 | prob.delet. | None | None | None | None | N |
| L/E | 0.5484 | ambiguous | 0.5002 | ambiguous | -1.074 | Destabilizing | 0.826 | D | 0.723 | prob.delet. | None | None | None | None | N |
| L/F | 0.1925 | likely_benign | 0.1562 | benign | -1.202 | Destabilizing | 0.638 | D | 0.585 | neutral | D | 0.5237867 | None | None | N |
| L/G | 0.8062 | likely_pathogenic | 0.7608 | pathogenic | -2.375 | Highly Destabilizing | 0.826 | D | 0.723 | prob.delet. | None | None | None | None | N |
| L/H | 0.3705 | ambiguous | 0.3176 | benign | -1.477 | Destabilizing | 0.976 | D | 0.718 | prob.delet. | N | 0.495433382 | None | None | N |
| L/I | 0.0732 | likely_benign | 0.0683 | benign | -0.856 | Destabilizing | 0.004 | N | 0.37 | neutral | N | 0.466487835 | None | None | N |
| L/K | 0.3915 | ambiguous | 0.345 | ambiguous | -1.432 | Destabilizing | 0.826 | D | 0.663 | neutral | None | None | None | None | N |
| L/M | 0.104 | likely_benign | 0.1028 | benign | -0.821 | Destabilizing | 0.057 | N | 0.376 | neutral | None | None | None | None | N |
| L/N | 0.6032 | likely_pathogenic | 0.5633 | ambiguous | -1.377 | Destabilizing | 0.935 | D | 0.719 | prob.delet. | None | None | None | None | N |
| L/P | 0.9334 | likely_pathogenic | 0.8991 | pathogenic | -1.195 | Destabilizing | 0.916 | D | 0.72 | prob.delet. | N | 0.513537637 | None | None | N |
| L/Q | 0.2511 | likely_benign | 0.23 | benign | -1.414 | Destabilizing | 0.826 | D | 0.661 | neutral | None | None | None | None | N |
| L/R | 0.3621 | ambiguous | 0.2973 | benign | -0.945 | Destabilizing | 0.781 | D | 0.661 | neutral | N | 0.513030657 | None | None | N |
| L/S | 0.6001 | likely_pathogenic | 0.5561 | ambiguous | -2.129 | Highly Destabilizing | 0.826 | D | 0.64 | neutral | None | None | None | None | N |
| L/T | 0.3577 | ambiguous | 0.3411 | ambiguous | -1.899 | Destabilizing | 0.7 | D | 0.615 | neutral | None | None | None | None | N |
| L/V | 0.0849 | likely_benign | 0.0841 | benign | -1.195 | Destabilizing | 0.034 | N | 0.503 | neutral | N | 0.454131827 | None | None | N |
| L/W | 0.3812 | ambiguous | 0.316 | benign | -1.275 | Destabilizing | 0.982 | D | 0.663 | neutral | None | None | None | None | N |
| L/Y | 0.408 | ambiguous | 0.3434 | ambiguous | -1.073 | Destabilizing | 0.826 | D | 0.636 | 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.