Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2473 | 7642;7643;7644 | chr2:178773639;178773638;178773637 | chr2:179638366;179638365;179638364 |
| N2AB | 2473 | 7642;7643;7644 | chr2:178773639;178773638;178773637 | chr2:179638366;179638365;179638364 |
| N2A | 2473 | 7642;7643;7644 | chr2:178773639;178773638;178773637 | chr2:179638366;179638365;179638364 |
| N2B | 2427 | 7504;7505;7506 | chr2:178773639;178773638;178773637 | chr2:179638366;179638365;179638364 |
| Novex-1 | 2427 | 7504;7505;7506 | chr2:178773639;178773638;178773637 | chr2:179638366;179638365;179638364 |
| Novex-2 | 2427 | 7504;7505;7506 | chr2:178773639;178773638;178773637 | chr2:179638366;179638365;179638364 |
| Novex-3 | 2473 | 7642;7643;7644 | chr2:178773639;178773638;178773637 | chr2:179638366;179638365;179638364 |
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/L | None | None | 0.521 | N | 0.463 | 0.198 | 0.52540932818 | gnomAD-4.0.0 | 1.59073E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85675E-06 | 0 | 0 |
| V/M | rs1204779013  |
-0.527 | 0.76 | N | 0.479 | 0.19 | 0.540288329166 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.83E-06 | 0 |
| V/M | rs1204779013 |
-0.527 | 0.76 | N | 0.479 | 0.19 | 0.540288329166 | gnomAD-4.0.0 | 4.77218E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.57025E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.5841 | likely_pathogenic | 0.5788 | pathogenic | -1.122 | Destabilizing | 0.939 | D | 0.596 | neutral | N | 0.506793723 | None | None | N |
| V/C | 0.9156 | likely_pathogenic | 0.9096 | pathogenic | -0.966 | Destabilizing | 0.999 | D | 0.706 | prob.neutral | None | None | None | None | N |
| V/D | 0.9395 | likely_pathogenic | 0.945 | pathogenic | -0.69 | Destabilizing | 0.998 | D | 0.773 | deleterious | None | None | None | None | N |
| V/E | 0.8987 | likely_pathogenic | 0.9052 | pathogenic | -0.698 | Destabilizing | 0.991 | D | 0.741 | deleterious | N | 0.496718696 | None | None | N |
| V/F | 0.524 | ambiguous | 0.5419 | ambiguous | -0.831 | Destabilizing | 0.986 | D | 0.738 | prob.delet. | None | None | None | None | N |
| V/G | 0.7429 | likely_pathogenic | 0.7537 | pathogenic | -1.416 | Destabilizing | 0.991 | D | 0.761 | deleterious | D | 0.575633039 | None | None | N |
| V/H | 0.9622 | likely_pathogenic | 0.9628 | pathogenic | -0.882 | Destabilizing | 0.999 | D | 0.743 | deleterious | None | None | None | None | N |
| V/I | 0.1012 | likely_benign | 0.0987 | benign | -0.433 | Destabilizing | 0.214 | N | 0.337 | neutral | None | None | None | None | N |
| V/K | 0.9268 | likely_pathogenic | 0.933 | pathogenic | -1.03 | Destabilizing | 0.993 | D | 0.734 | prob.delet. | None | None | None | None | N |
| V/L | 0.5166 | ambiguous | 0.5099 | ambiguous | -0.433 | Destabilizing | 0.521 | D | 0.463 | neutral | N | 0.509024163 | None | None | N |
| V/M | 0.3607 | ambiguous | 0.3568 | ambiguous | -0.499 | Destabilizing | 0.76 | D | 0.479 | neutral | N | 0.508354036 | None | None | N |
| V/N | 0.8502 | likely_pathogenic | 0.8536 | pathogenic | -0.842 | Destabilizing | 0.998 | D | 0.769 | deleterious | None | None | None | None | N |
| V/P | 0.9551 | likely_pathogenic | 0.9564 | pathogenic | -0.627 | Destabilizing | 0.998 | D | 0.746 | deleterious | None | None | None | None | N |
| V/Q | 0.9051 | likely_pathogenic | 0.9077 | pathogenic | -0.957 | Destabilizing | 0.993 | D | 0.752 | deleterious | None | None | None | None | N |
| V/R | 0.9038 | likely_pathogenic | 0.9124 | pathogenic | -0.57 | Destabilizing | 0.993 | D | 0.773 | deleterious | None | None | None | None | N |
| V/S | 0.7546 | likely_pathogenic | 0.7501 | pathogenic | -1.366 | Destabilizing | 0.993 | D | 0.701 | prob.neutral | None | None | None | None | N |
| V/T | 0.604 | likely_pathogenic | 0.5886 | pathogenic | -1.249 | Destabilizing | 0.953 | D | 0.661 | neutral | None | None | None | None | N |
| V/W | 0.9841 | likely_pathogenic | 0.9849 | pathogenic | -0.985 | Destabilizing | 0.999 | D | 0.732 | prob.delet. | None | None | None | None | N |
| V/Y | 0.9101 | likely_pathogenic | 0.9148 | pathogenic | -0.692 | Destabilizing | 0.993 | D | 0.739 | prob.delet. | 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.