Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 8504 | 25735;25736;25737 | chr2:178717224;178717223;178717222 | chr2:179581951;179581950;179581949 |
| N2AB | 8187 | 24784;24785;24786 | chr2:178717224;178717223;178717222 | chr2:179581951;179581950;179581949 |
| N2A | 7260 | 22003;22004;22005 | chr2:178717224;178717223;178717222 | chr2:179581951;179581950;179581949 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/K | None | None | 0.156 | D | 0.407 | 0.54 | 0.651558712581 | gnomAD-4.0.0 | 1.59164E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.8591E-06 | 0 | 0 |
| M/L | rs761929830  |
-0.799 | None | N | 0.056 | 0.226 | 0.595302103986 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | N | None | 0 | 1.15949E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| M/L | rs761929830 |
-0.799 | None | N | 0.056 | 0.226 | 0.595302103986 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 1.96489E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| M/L | rs761929830 |
-0.799 | None | N | 0.056 | 0.226 | 0.595302103986 | gnomAD-4.0.0 | 1.02505E-05 | None | None | None | None | N | None | 0 | 1.35589E-04 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| M/V | rs761929830 |
None | 0.073 | N | 0.261 | 0.197 | 0.444807159249 | gnomAD-4.0.0 | 2.56224E-06 | None | None | None | None | N | None | 0 | 1.69428E-05 | None | 0 | 0 | None | 0 | 0 | 2.39367E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.8155 | likely_pathogenic | 0.8372 | pathogenic | -1.88 | Destabilizing | 0.536 | D | 0.313 | neutral | None | None | None | None | N |
| M/C | 0.9435 | likely_pathogenic | 0.9532 | pathogenic | -1.325 | Destabilizing | 0.993 | D | 0.521 | neutral | None | None | None | None | N |
| M/D | 0.9846 | likely_pathogenic | 0.9875 | pathogenic | -0.432 | Destabilizing | 0.796 | D | 0.623 | neutral | None | None | None | None | N |
| M/E | 0.8938 | likely_pathogenic | 0.9153 | pathogenic | -0.355 | Destabilizing | 0.437 | N | 0.515 | neutral | None | None | None | None | N |
| M/F | 0.4778 | ambiguous | 0.4841 | ambiguous | -0.763 | Destabilizing | 0.23 | N | 0.355 | neutral | None | None | None | None | N |
| M/G | 0.9429 | likely_pathogenic | 0.949 | pathogenic | -2.248 | Highly Destabilizing | 0.929 | D | 0.535 | neutral | None | None | None | None | N |
| M/H | 0.8975 | likely_pathogenic | 0.9125 | pathogenic | -1.374 | Destabilizing | 0.983 | D | 0.571 | neutral | None | None | None | None | N |
| M/I | 0.2714 | likely_benign | 0.2817 | benign | -0.901 | Destabilizing | None | N | 0.059 | neutral | N | 0.363051249 | None | None | N |
| M/K | 0.688 | likely_pathogenic | 0.7141 | pathogenic | -0.545 | Destabilizing | 0.156 | N | 0.407 | neutral | D | 0.531982109 | None | None | N |
| M/L | 0.1857 | likely_benign | 0.1931 | benign | -0.901 | Destabilizing | None | N | 0.056 | neutral | N | 0.465274327 | None | None | N |
| M/N | 0.8809 | likely_pathogenic | 0.8972 | pathogenic | -0.491 | Destabilizing | 0.796 | D | 0.585 | neutral | None | None | None | None | N |
| M/P | 0.9787 | likely_pathogenic | 0.9812 | pathogenic | -1.201 | Destabilizing | 0.977 | D | 0.614 | neutral | None | None | None | None | N |
| M/Q | 0.6852 | likely_pathogenic | 0.7152 | pathogenic | -0.464 | Destabilizing | 0.727 | D | 0.431 | neutral | None | None | None | None | N |
| M/R | 0.7132 | likely_pathogenic | 0.7407 | pathogenic | -0.25 | Destabilizing | 0.006 | N | 0.233 | neutral | N | 0.504411505 | None | None | N |
| M/S | 0.8574 | likely_pathogenic | 0.8773 | pathogenic | -1.17 | Destabilizing | 0.843 | D | 0.447 | neutral | None | None | None | None | N |
| M/T | 0.6428 | likely_pathogenic | 0.6835 | pathogenic | -0.964 | Destabilizing | 0.375 | N | 0.409 | neutral | N | 0.478763699 | None | None | N |
| M/V | 0.1538 | likely_benign | 0.1593 | benign | -1.201 | Destabilizing | 0.073 | N | 0.261 | neutral | N | 0.425790432 | None | None | N |
| M/W | 0.8525 | likely_pathogenic | 0.8682 | pathogenic | -0.732 | Destabilizing | 0.999 | D | 0.504 | neutral | None | None | None | None | N |
| M/Y | 0.7811 | likely_pathogenic | 0.8001 | pathogenic | -0.753 | Destabilizing | 0.987 | D | 0.563 | 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.