Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23604 | 71035;71036;71037 | chr2:178575322;178575321;178575320 | chr2:179440049;179440048;179440047 |
| N2AB | 21963 | 66112;66113;66114 | chr2:178575322;178575321;178575320 | chr2:179440049;179440048;179440047 |
| N2A | 21036 | 63331;63332;63333 | chr2:178575322;178575321;178575320 | chr2:179440049;179440048;179440047 |
| N2B | 14539 | 43840;43841;43842 | chr2:178575322;178575321;178575320 | chr2:179440049;179440048;179440047 |
| Novex-1 | 14664 | 44215;44216;44217 | chr2:178575322;178575321;178575320 | chr2:179440049;179440048;179440047 |
| Novex-2 | 14731 | 44416;44417;44418 | chr2:178575322;178575321;178575320 | chr2:179440049;179440048;179440047 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Q/E | rs747651345  |
-2.129 | 0.472 | N | 0.417 | 0.255 | 0.284150004643 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| Q/E | rs747651345 |
-2.129 | 0.472 | N | 0.417 | 0.255 | 0.284150004643 | 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 |
| Q/E | rs747651345 |
-2.129 | 0.472 | N | 0.417 | 0.255 | 0.284150004643 | gnomAD-4.0.0 | 2.47935E-06 | None | None | None | None | N | None | 4.00598E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.60138E-05 |
| Q/L | rs780611891 |
-0.663 | 0.684 | N | 0.62 | 0.289 | 0.441949972293 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| Q/P | None | None | 0.979 | N | 0.678 | 0.377 | 0.381409048467 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.625E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Q/A | 0.3498 | ambiguous | 0.4021 | ambiguous | -1.983 | Destabilizing | 0.543 | D | 0.558 | neutral | None | None | None | None | N |
| Q/C | 0.6094 | likely_pathogenic | 0.6377 | pathogenic | -1.381 | Destabilizing | 0.996 | D | 0.673 | neutral | None | None | None | None | N |
| Q/D | 0.9013 | likely_pathogenic | 0.9234 | pathogenic | -2.401 | Highly Destabilizing | 0.854 | D | 0.547 | neutral | None | None | None | None | N |
| Q/E | 0.1862 | likely_benign | 0.1899 | benign | -2.093 | Highly Destabilizing | 0.472 | N | 0.417 | neutral | N | 0.494679222 | None | None | N |
| Q/F | 0.8766 | likely_pathogenic | 0.8841 | pathogenic | -1.184 | Destabilizing | 0.953 | D | 0.649 | neutral | None | None | None | None | N |
| Q/G | 0.5604 | ambiguous | 0.6185 | pathogenic | -2.373 | Highly Destabilizing | 0.742 | D | 0.616 | neutral | None | None | None | None | N |
| Q/H | 0.3481 | ambiguous | 0.3772 | ambiguous | -1.794 | Destabilizing | 0.007 | N | 0.347 | neutral | N | 0.512016976 | None | None | N |
| Q/I | 0.6445 | likely_pathogenic | 0.6646 | pathogenic | -0.875 | Destabilizing | 0.953 | D | 0.669 | neutral | None | None | None | None | N |
| Q/K | 0.1664 | likely_benign | 0.1752 | benign | -1.402 | Destabilizing | 0.309 | N | 0.387 | neutral | N | 0.444213117 | None | None | N |
| Q/L | 0.2489 | likely_benign | 0.2842 | benign | -0.875 | Destabilizing | 0.684 | D | 0.62 | neutral | N | 0.487505321 | None | None | N |
| Q/M | 0.4972 | ambiguous | 0.5327 | ambiguous | -0.9 | Destabilizing | 0.984 | D | 0.612 | neutral | None | None | None | None | N |
| Q/N | 0.6436 | likely_pathogenic | 0.6865 | pathogenic | -2.063 | Highly Destabilizing | 0.742 | D | 0.512 | neutral | None | None | None | None | N |
| Q/P | 0.9523 | likely_pathogenic | 0.9522 | pathogenic | -1.228 | Destabilizing | 0.979 | D | 0.678 | prob.neutral | N | 0.481777265 | None | None | N |
| Q/R | 0.1057 | likely_benign | 0.1088 | benign | -1.563 | Destabilizing | 0.001 | N | 0.161 | neutral | N | 0.304970446 | None | None | N |
| Q/S | 0.4318 | ambiguous | 0.482 | ambiguous | -2.4 | Highly Destabilizing | 0.543 | D | 0.452 | neutral | None | None | None | None | N |
| Q/T | 0.3986 | ambiguous | 0.4573 | ambiguous | -1.959 | Destabilizing | 0.742 | D | 0.636 | neutral | None | None | None | None | N |
| Q/V | 0.4598 | ambiguous | 0.4828 | ambiguous | -1.228 | Destabilizing | 0.854 | D | 0.646 | neutral | None | None | None | None | N |
| Q/W | 0.7899 | likely_pathogenic | 0.7918 | pathogenic | -1.354 | Destabilizing | 0.996 | D | 0.644 | neutral | None | None | None | None | N |
| Q/Y | 0.6984 | likely_pathogenic | 0.7088 | pathogenic | -1.068 | Destabilizing | 0.91 | D | 0.684 | 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.