Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 13975 | 42148;42149;42150 | chr2:178635266;178635265;178635264 | chr2:179499993;179499992;179499991 |
| N2AB | 12334 | 37225;37226;37227 | chr2:178635266;178635265;178635264 | chr2:179499993;179499992;179499991 |
| N2A | 11407 | 34444;34445;34446 | chr2:178635266;178635265;178635264 | chr2:179499993;179499992;179499991 |
| N2B | 4910 | 14953;14954;14955 | chr2:178635266;178635265;178635264 | chr2:179499993;179499992;179499991 |
| Novex-1 | 5035 | 15328;15329;15330 | chr2:178635266;178635265;178635264 | chr2:179499993;179499992;179499991 |
| Novex-2 | 5102 | 15529;15530;15531 | chr2:178635266;178635265;178635264 | chr2:179499993;179499992;179499991 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs1417052657  |
0.088 | 0.966 | N | 0.524 | 0.226 | 0.244539031024 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/I | rs1417052657 |
0.088 | 0.966 | N | 0.524 | 0.226 | 0.244539031024 | gnomAD-4.0.0 | 1.31572E-05 | None | None | None | None | N | None | 4.82952E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/N | rs1417052657 |
-0.517 | 0.799 | N | 0.457 | 0.15 | 0.197625483188 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| T/N | rs1417052657 |
-0.517 | 0.799 | N | 0.457 | 0.15 | 0.197625483188 | gnomAD-4.0.0 | 1.36884E-06 | None | None | None | None | N | None | 0 | 2.23674E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15964E-05 | 0 |
| T/S | None | None | 0.622 | N | 0.503 | 0.114 | 0.126345400529 | gnomAD-4.0.0 | 1.36884E-06 | None | None | None | None | N | None | 5.98122E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1863 | likely_benign | 0.1783 | benign | -0.459 | Destabilizing | 0.622 | D | 0.373 | neutral | N | 0.438069444 | None | None | N |
| T/C | 0.7484 | likely_pathogenic | 0.721 | pathogenic | -0.445 | Destabilizing | 0.998 | D | 0.559 | neutral | None | None | None | None | N |
| T/D | 0.7341 | likely_pathogenic | 0.6857 | pathogenic | 0.309 | Stabilizing | 0.522 | D | 0.451 | neutral | None | None | None | None | N |
| T/E | 0.4497 | ambiguous | 0.4161 | ambiguous | 0.294 | Stabilizing | 0.002 | N | 0.289 | neutral | None | None | None | None | N |
| T/F | 0.6489 | likely_pathogenic | 0.6026 | pathogenic | -0.722 | Destabilizing | 0.991 | D | 0.723 | deleterious | None | None | None | None | N |
| T/G | 0.6858 | likely_pathogenic | 0.6384 | pathogenic | -0.669 | Destabilizing | 0.915 | D | 0.533 | neutral | None | None | None | None | N |
| T/H | 0.5951 | likely_pathogenic | 0.5538 | ambiguous | -0.87 | Destabilizing | 0.974 | D | 0.707 | prob.delet. | None | None | None | None | N |
| T/I | 0.3504 | ambiguous | 0.3212 | benign | -0.011 | Destabilizing | 0.966 | D | 0.524 | neutral | N | 0.438160858 | None | None | N |
| T/K | 0.5871 | likely_pathogenic | 0.5279 | ambiguous | -0.407 | Destabilizing | 0.725 | D | 0.451 | neutral | None | None | None | None | N |
| T/L | 0.2769 | likely_benign | 0.28 | benign | -0.011 | Destabilizing | 0.841 | D | 0.426 | neutral | None | None | None | None | N |
| T/M | 0.1683 | likely_benign | 0.1669 | benign | -0.05 | Destabilizing | 0.998 | D | 0.534 | neutral | None | None | None | None | N |
| T/N | 0.3081 | likely_benign | 0.2785 | benign | -0.385 | Destabilizing | 0.799 | D | 0.457 | neutral | N | 0.441175787 | None | None | N |
| T/P | 0.6036 | likely_pathogenic | 0.6037 | pathogenic | -0.128 | Destabilizing | 0.966 | D | 0.486 | neutral | N | 0.427981387 | None | None | N |
| T/Q | 0.4267 | ambiguous | 0.409 | ambiguous | -0.479 | Destabilizing | 0.725 | D | 0.503 | neutral | None | None | None | None | N |
| T/R | 0.5671 | likely_pathogenic | 0.507 | ambiguous | -0.216 | Destabilizing | 0.949 | D | 0.488 | neutral | None | None | None | None | N |
| T/S | 0.2557 | likely_benign | 0.2338 | benign | -0.647 | Destabilizing | 0.622 | D | 0.503 | neutral | N | 0.439058873 | None | None | N |
| T/V | 0.2351 | likely_benign | 0.2117 | benign | -0.128 | Destabilizing | 0.915 | D | 0.375 | neutral | None | None | None | None | N |
| T/W | 0.9162 | likely_pathogenic | 0.8865 | pathogenic | -0.73 | Destabilizing | 0.998 | D | 0.769 | deleterious | None | None | None | None | N |
| T/Y | 0.7158 | likely_pathogenic | 0.6644 | pathogenic | -0.438 | Destabilizing | 0.991 | D | 0.716 | 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.