Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29577 | 88954;88955;88956 | chr2:178554618;178554617;178554616 | chr2:179419345;179419344;179419343 |
| N2AB | 27936 | 84031;84032;84033 | chr2:178554618;178554617;178554616 | chr2:179419345;179419344;179419343 |
| N2A | 27009 | 81250;81251;81252 | chr2:178554618;178554617;178554616 | chr2:179419345;179419344;179419343 |
| N2B | 20512 | 61759;61760;61761 | chr2:178554618;178554617;178554616 | chr2:179419345;179419344;179419343 |
| Novex-1 | 20637 | 62134;62135;62136 | chr2:178554618;178554617;178554616 | chr2:179419345;179419344;179419343 |
| Novex-2 | 20704 | 62335;62336;62337 | chr2:178554618;178554617;178554616 | chr2:179419345;179419344;179419343 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/C | rs1559230996  |
None | 1.0 | N | 0.683 | 0.596 | 0.530606565545 | gnomAD-4.0.0 | 4.77307E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.88232E-05 | 0 | 0 | 0 | 6.04778E-05 |
| S/N | None | None | 0.999 | N | 0.472 | 0.195 | 0.21279746466 | gnomAD-4.0.0 | 1.59103E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.02371E-05 |
| S/R | None | None | 1.0 | N | 0.595 | 0.496 | 0.399449838166 | gnomAD-4.0.0 | 6.84167E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.51965E-05 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.33 | likely_benign | 0.3151 | benign | -0.197 | Destabilizing | 0.998 | D | 0.419 | neutral | None | None | None | None | N |
| S/C | 0.6146 | likely_pathogenic | 0.5709 | pathogenic | -0.369 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | N | 0.495526654 | None | None | N |
| S/D | 0.9575 | likely_pathogenic | 0.9466 | pathogenic | -0.033 | Destabilizing | 0.999 | D | 0.492 | neutral | None | None | None | None | N |
| S/E | 0.9715 | likely_pathogenic | 0.9653 | pathogenic | -0.145 | Destabilizing | 0.999 | D | 0.485 | neutral | None | None | None | None | N |
| S/F | 0.9209 | likely_pathogenic | 0.9095 | pathogenic | -0.888 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | N |
| S/G | 0.4085 | ambiguous | 0.3703 | ambiguous | -0.254 | Destabilizing | 0.999 | D | 0.427 | neutral | N | 0.426048643 | None | None | N |
| S/H | 0.9126 | likely_pathogenic | 0.9029 | pathogenic | -0.603 | Destabilizing | 1.0 | D | 0.69 | prob.neutral | None | None | None | None | N |
| S/I | 0.8929 | likely_pathogenic | 0.8732 | pathogenic | -0.181 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | N | 0.488689799 | None | None | N |
| S/K | 0.988 | likely_pathogenic | 0.987 | pathogenic | -0.441 | Destabilizing | 0.999 | D | 0.486 | neutral | None | None | None | None | N |
| S/L | 0.614 | likely_pathogenic | 0.5807 | pathogenic | -0.181 | Destabilizing | 1.0 | D | 0.571 | neutral | None | None | None | None | N |
| S/M | 0.7904 | likely_pathogenic | 0.7647 | pathogenic | -0.081 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | N |
| S/N | 0.7519 | likely_pathogenic | 0.7079 | pathogenic | -0.185 | Destabilizing | 0.999 | D | 0.472 | neutral | N | 0.477938901 | None | None | N |
| S/P | 0.943 | likely_pathogenic | 0.9353 | pathogenic | -0.161 | Destabilizing | 1.0 | D | 0.599 | neutral | None | None | None | None | N |
| S/Q | 0.9385 | likely_pathogenic | 0.9309 | pathogenic | -0.449 | Destabilizing | 1.0 | D | 0.597 | neutral | None | None | None | None | N |
| S/R | 0.9775 | likely_pathogenic | 0.9779 | pathogenic | -0.156 | Destabilizing | 1.0 | D | 0.595 | neutral | N | 0.514305133 | None | None | N |
| S/T | 0.3421 | ambiguous | 0.3052 | benign | -0.305 | Destabilizing | 0.999 | D | 0.415 | neutral | N | 0.498586319 | None | None | N |
| S/V | 0.8385 | likely_pathogenic | 0.8119 | pathogenic | -0.161 | Destabilizing | 1.0 | D | 0.657 | neutral | None | None | None | None | N |
| S/W | 0.9284 | likely_pathogenic | 0.9238 | pathogenic | -0.941 | Destabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | N |
| S/Y | 0.8891 | likely_pathogenic | 0.8742 | pathogenic | -0.639 | Destabilizing | 1.0 | D | 0.738 | 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.