Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20384 | 61375;61376;61377 | chr2:178590575;178590574;178590573 | chr2:179455302;179455301;179455300 |
| N2AB | 18743 | 56452;56453;56454 | chr2:178590575;178590574;178590573 | chr2:179455302;179455301;179455300 |
| N2A | 17816 | 53671;53672;53673 | chr2:178590575;178590574;178590573 | chr2:179455302;179455301;179455300 |
| N2B | 11319 | 34180;34181;34182 | chr2:178590575;178590574;178590573 | chr2:179455302;179455301;179455300 |
| Novex-1 | 11444 | 34555;34556;34557 | chr2:178590575;178590574;178590573 | chr2:179455302;179455301;179455300 |
| Novex-2 | 11511 | 34756;34757;34758 | chr2:178590575;178590574;178590573 | chr2:179455302;179455301;179455300 |
| 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 | rs778981748  |
-0.477 | 0.931 | N | 0.522 | 0.284 | 0.319970858106 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.93E-06 | 0 |
| S/C | rs778981748 |
-0.477 | 0.931 | N | 0.522 | 0.284 | 0.319970858106 | gnomAD-4.0.0 | 1.36943E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79973E-06 | 0 | 0 |
| S/G | None | None | 0.334 | N | 0.424 | 0.125 | 0.104622674875 | gnomAD-4.0.0 | 6.84714E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99866E-07 | 0 | 0 |
| S/N | rs771365105 |
-1.065 | 0.334 | N | 0.489 | 0.101 | 0.0482279557977 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 6.5E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/N | rs771365105 |
-1.065 | 0.334 | N | 0.489 | 0.101 | 0.0482279557977 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/N | rs771365105 |
-1.065 | 0.334 | N | 0.489 | 0.101 | 0.0482279557977 | gnomAD-4.0.0 | 2.56651E-06 | None | None | None | None | N | None | 1.69388E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.39646E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.3102 | likely_benign | 0.3297 | benign | -0.366 | Destabilizing | 0.121 | N | 0.409 | neutral | None | None | None | None | N |
| S/C | 0.2322 | likely_benign | 0.2397 | benign | -0.447 | Destabilizing | 0.931 | D | 0.522 | neutral | N | 0.497335582 | None | None | N |
| S/D | 0.604 | likely_pathogenic | 0.5611 | ambiguous | -1.283 | Destabilizing | 0.399 | N | 0.474 | neutral | None | None | None | None | N |
| S/E | 0.8911 | likely_pathogenic | 0.8723 | pathogenic | -1.266 | Destabilizing | 0.399 | N | 0.476 | neutral | None | None | None | None | N |
| S/F | 0.7594 | likely_pathogenic | 0.7203 | pathogenic | -0.527 | Destabilizing | 0.826 | D | 0.604 | neutral | None | None | None | None | N |
| S/G | 0.1503 | likely_benign | 0.1555 | benign | -0.631 | Destabilizing | 0.334 | N | 0.424 | neutral | N | 0.479738694 | None | None | N |
| S/H | 0.7118 | likely_pathogenic | 0.6547 | pathogenic | -1.235 | Destabilizing | 0.982 | D | 0.524 | neutral | None | None | None | None | N |
| S/I | 0.8037 | likely_pathogenic | 0.765 | pathogenic | 0.232 | Stabilizing | 0.468 | N | 0.591 | neutral | N | 0.465241675 | None | None | N |
| S/K | 0.9257 | likely_pathogenic | 0.8943 | pathogenic | -0.824 | Destabilizing | 0.399 | N | 0.478 | neutral | None | None | None | None | N |
| S/L | 0.4282 | ambiguous | 0.3888 | ambiguous | 0.232 | Stabilizing | 0.25 | N | 0.492 | neutral | None | None | None | None | N |
| S/M | 0.4736 | ambiguous | 0.4617 | ambiguous | 0.55 | Stabilizing | 0.947 | D | 0.529 | neutral | None | None | None | None | N |
| S/N | 0.2403 | likely_benign | 0.2131 | benign | -0.999 | Destabilizing | 0.334 | N | 0.489 | neutral | N | 0.491033124 | None | None | N |
| S/P | 0.961 | likely_pathogenic | 0.9589 | pathogenic | 0.067 | Stabilizing | 0.826 | D | 0.544 | neutral | None | None | None | None | N |
| S/Q | 0.8447 | likely_pathogenic | 0.8192 | pathogenic | -1.162 | Destabilizing | 0.826 | D | 0.52 | neutral | None | None | None | None | N |
| S/R | 0.9069 | likely_pathogenic | 0.8793 | pathogenic | -0.703 | Destabilizing | 0.638 | D | 0.541 | neutral | N | 0.494305502 | None | None | N |
| S/T | 0.0624 | likely_benign | 0.0702 | benign | -0.791 | Destabilizing | 0.001 | N | 0.203 | neutral | N | 0.411761476 | None | None | N |
| S/V | 0.7249 | likely_pathogenic | 0.6992 | pathogenic | 0.067 | Stabilizing | 0.25 | N | 0.497 | neutral | None | None | None | None | N |
| S/W | 0.7975 | likely_pathogenic | 0.7632 | pathogenic | -0.648 | Destabilizing | 0.982 | D | 0.627 | neutral | None | None | None | None | N |
| S/Y | 0.5903 | likely_pathogenic | 0.5395 | ambiguous | -0.315 | Destabilizing | 0.826 | D | 0.604 | 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.