Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 8318 | 25177;25178;25179 | chr2:178718054;178718053;178718052 | chr2:179582781;179582780;179582779 |
| N2AB | 8001 | 24226;24227;24228 | chr2:178718054;178718053;178718052 | chr2:179582781;179582780;179582779 |
| N2A | 7074 | 21445;21446;21447 | chr2:178718054;178718053;178718052 | chr2:179582781;179582780;179582779 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/I | rs200103997  |
-0.731 | 0.008 | N | 0.189 | 0.063 | None | gnomAD-2.1.1 | 5.74659E-04 | None | None | None | None | N | None | 8.27E-05 | 2.83E-05 | None | 0 | 0 | None | 0 | None | 3.19872E-04 | 1.14055E-03 | 5.61798E-04 |
| V/I | rs200103997 |
-0.731 | 0.008 | N | 0.189 | 0.063 | None | gnomAD-3.1.2 | 5.45572E-04 | None | None | None | None | N | None | 4.82E-05 | 6.55E-05 | 0 | 0 | 0 | None | 9.43E-05 | 0 | 1.14703E-03 | 0 | 4.78011E-04 |
| V/I | rs200103997 |
-0.731 | 0.008 | N | 0.189 | 0.063 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| V/I | rs200103997 |
-0.731 | 0.008 | N | 0.189 | 0.063 | None | gnomAD-4.0.0 | 7.49198E-04 | None | None | None | None | N | None | 9.32935E-05 | 1.33316E-04 | None | 0 | 2.22856E-05 | None | 2.18757E-04 | 0 | 9.73976E-04 | 0 | 4.80169E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.2142 | likely_benign | 0.2962 | benign | -1.744 | Destabilizing | 0.378 | N | 0.375 | neutral | D | 0.531075245 | None | None | N |
| V/C | 0.7604 | likely_pathogenic | 0.809 | pathogenic | -1.196 | Destabilizing | 0.997 | D | 0.554 | neutral | None | None | None | None | N |
| V/D | 0.4108 | ambiguous | 0.5228 | ambiguous | -1.881 | Destabilizing | 0.879 | D | 0.628 | neutral | N | 0.495615877 | None | None | N |
| V/E | 0.2755 | likely_benign | 0.3138 | benign | -1.857 | Destabilizing | 0.608 | D | 0.569 | neutral | None | None | None | None | N |
| V/F | 0.1661 | likely_benign | 0.2048 | benign | -1.346 | Destabilizing | 0.98 | D | 0.603 | neutral | N | 0.483579643 | None | None | N |
| V/G | 0.3739 | ambiguous | 0.5169 | ambiguous | -2.095 | Highly Destabilizing | 0.907 | D | 0.605 | neutral | N | 0.466314477 | None | None | N |
| V/H | 0.4852 | ambiguous | 0.5639 | ambiguous | -1.667 | Destabilizing | 0.998 | D | 0.593 | neutral | None | None | None | None | N |
| V/I | 0.0644 | likely_benign | 0.0654 | benign | -0.856 | Destabilizing | 0.008 | N | 0.189 | neutral | N | 0.465639687 | None | None | N |
| V/K | 0.3023 | likely_benign | 0.343 | ambiguous | -1.41 | Destabilizing | 0.772 | D | 0.569 | neutral | None | None | None | None | N |
| V/L | 0.1863 | likely_benign | 0.2252 | benign | -0.856 | Destabilizing | 0.002 | N | 0.181 | neutral | N | 0.491999569 | None | None | N |
| V/M | 0.1234 | likely_benign | 0.1434 | benign | -0.646 | Destabilizing | 0.948 | D | 0.578 | neutral | None | None | None | None | N |
| V/N | 0.2811 | likely_benign | 0.3683 | ambiguous | -1.252 | Destabilizing | 0.638 | D | 0.629 | neutral | None | None | None | None | N |
| V/P | 0.9675 | likely_pathogenic | 0.9865 | pathogenic | -1.119 | Destabilizing | 0.782 | D | 0.589 | neutral | None | None | None | None | N |
| V/Q | 0.3018 | likely_benign | 0.3501 | ambiguous | -1.419 | Destabilizing | 0.945 | D | 0.565 | neutral | None | None | None | None | N |
| V/R | 0.2643 | likely_benign | 0.3207 | benign | -0.899 | Destabilizing | 0.981 | D | 0.607 | neutral | None | None | None | None | N |
| V/S | 0.2519 | likely_benign | 0.3436 | ambiguous | -1.778 | Destabilizing | 0.06 | N | 0.348 | neutral | None | None | None | None | N |
| V/T | 0.148 | likely_benign | 0.1723 | benign | -1.647 | Destabilizing | 0.009 | N | 0.163 | neutral | None | None | None | None | N |
| V/W | 0.7603 | likely_pathogenic | 0.8223 | pathogenic | -1.588 | Destabilizing | 0.999 | D | 0.619 | neutral | None | None | None | None | N |
| V/Y | 0.4862 | ambiguous | 0.5505 | ambiguous | -1.297 | Destabilizing | 0.981 | D | 0.588 | 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.