Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32987 | 99184;99185;99186 | chr2:178538976;178538975;178538974 | chr2:179403703;179403702;179403701 |
| N2AB | 31346 | 94261;94262;94263 | chr2:178538976;178538975;178538974 | chr2:179403703;179403702;179403701 |
| N2A | 30419 | 91480;91481;91482 | chr2:178538976;178538975;178538974 | chr2:179403703;179403702;179403701 |
| N2B | 23922 | 71989;71990;71991 | chr2:178538976;178538975;178538974 | chr2:179403703;179403702;179403701 |
| Novex-1 | 24047 | 72364;72365;72366 | chr2:178538976;178538975;178538974 | chr2:179403703;179403702;179403701 |
| Novex-2 | 24114 | 72565;72566;72567 | chr2:178538976;178538975;178538974 | chr2:179403703;179403702;179403701 |
| 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/F | rs746380940  |
-0.776 | 0.999 | D | 0.695 | 0.412 | None | gnomAD-2.1.1 | 8.96E-05 | None | None | None | None | I | None | 0 | 5.67E-05 | None | 0 | 0 | None | 0 | None | 0 | 1.72826E-04 | 1.40964E-04 |
| S/F | rs746380940 |
-0.776 | 0.999 | D | 0.695 | 0.412 | None | gnomAD-3.1.2 | 1.44585E-04 | None | None | None | None | I | None | 0 | 1.30993E-04 | 0 | 0 | 0 | None | 0 | 0 | 2.79346E-04 | 0 | 4.78011E-04 |
| S/F | rs746380940 |
-0.776 | 0.999 | D | 0.695 | 0.412 | None | gnomAD-4.0.0 | 1.29149E-04 | None | None | None | None | I | None | 0 | 6.67379E-05 | None | 0 | 0 | None | 0 | 0 | 1.69053E-04 | 0 | 8.02723E-05 |
| S/P | rs758494581 |
0.099 | 0.999 | N | 0.562 | 0.532 | None | gnomAD-2.1.1 | 8.96E-05 | None | None | None | None | I | None | 0 | 5.67E-05 | None | 0 | 0 | None | 0 | None | 0 | 1.72747E-04 | 1.40924E-04 |
| S/P | rs758494581 |
0.099 | 0.999 | N | 0.562 | 0.532 | None | gnomAD-3.1.2 | 1.44549E-04 | None | None | None | None | I | None | 0 | 1.30959E-04 | 0 | 0 | 0 | None | 0 | 0 | 2.79297E-04 | 0 | 4.77555E-04 |
| S/P | rs758494581 |
0.099 | 0.999 | N | 0.562 | 0.532 | None | gnomAD-4.0.0 | 1.29121E-04 | None | None | None | None | I | None | 0 | 6.67289E-05 | None | 0 | 0 | None | 0 | 0 | 1.69013E-04 | 0 | 8.02388E-05 |
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 | 0.4035 | ambiguous | 0.3264 | benign | -0.66 | Destabilizing | 0.944 | D | 0.455 | neutral | N | 0.494586191 | None | None | I |
| S/C | 0.5203 | ambiguous | 0.3927 | ambiguous | -0.484 | Destabilizing | 1.0 | D | 0.565 | neutral | D | 0.530429534 | None | None | I |
| S/D | 0.9877 | likely_pathogenic | 0.9804 | pathogenic | -0.892 | Destabilizing | 0.991 | D | 0.5 | neutral | None | None | None | None | I |
| S/E | 0.9941 | likely_pathogenic | 0.9896 | pathogenic | -0.784 | Destabilizing | 0.991 | D | 0.509 | neutral | None | None | None | None | I |
| S/F | 0.9829 | likely_pathogenic | 0.964 | pathogenic | -0.457 | Destabilizing | 0.999 | D | 0.695 | prob.delet. | D | 0.530176044 | None | None | I |
| S/G | 0.4937 | ambiguous | 0.403 | ambiguous | -1.021 | Destabilizing | 0.991 | D | 0.376 | neutral | None | None | None | None | I |
| S/H | 0.9876 | likely_pathogenic | 0.9798 | pathogenic | -1.48 | Destabilizing | 1.0 | D | 0.537 | neutral | None | None | None | None | I |
| S/I | 0.9503 | likely_pathogenic | 0.9002 | pathogenic | 0.225 | Stabilizing | 0.995 | D | 0.685 | prob.delet. | None | None | None | None | I |
| S/K | 0.9989 | likely_pathogenic | 0.9979 | pathogenic | -0.659 | Destabilizing | 0.991 | D | 0.499 | neutral | None | None | None | None | I |
| S/L | 0.8073 | likely_pathogenic | 0.6912 | pathogenic | 0.225 | Stabilizing | 0.982 | D | 0.423 | neutral | None | None | None | None | I |
| S/M | 0.8671 | likely_pathogenic | 0.7954 | pathogenic | 0.271 | Stabilizing | 1.0 | D | 0.525 | neutral | None | None | None | None | I |
| S/N | 0.9345 | likely_pathogenic | 0.8983 | pathogenic | -0.965 | Destabilizing | 0.991 | D | 0.509 | neutral | None | None | None | None | I |
| S/P | 0.9921 | likely_pathogenic | 0.9856 | pathogenic | -0.033 | Destabilizing | 0.999 | D | 0.562 | neutral | N | 0.498082138 | None | None | I |
| S/Q | 0.9899 | likely_pathogenic | 0.9839 | pathogenic | -0.872 | Destabilizing | 0.999 | D | 0.567 | neutral | None | None | None | None | I |
| S/R | 0.998 | likely_pathogenic | 0.9962 | pathogenic | -0.837 | Destabilizing | 0.997 | D | 0.557 | neutral | None | None | None | None | I |
| S/T | 0.2021 | likely_benign | 0.172 | benign | -0.761 | Destabilizing | 0.355 | N | 0.237 | neutral | N | 0.484414661 | None | None | I |
| S/V | 0.88 | likely_pathogenic | 0.7946 | pathogenic | -0.033 | Destabilizing | 0.995 | D | 0.385 | neutral | None | None | None | None | I |
| S/W | 0.9883 | likely_pathogenic | 0.9786 | pathogenic | -0.621 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | I |
| S/Y | 0.9824 | likely_pathogenic | 0.9647 | pathogenic | -0.264 | Destabilizing | 0.999 | D | 0.689 | prob.delet. | D | 0.529922555 | None | None | I |
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.