Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3984 | 12175;12176;12177 | chr2:178741283;178741282;178741281 | chr2:179606010;179606009;179606008 |
| N2AB | 3667 | 11224;11225;11226 | chr2:178741283;178741282;178741281 | chr2:179606010;179606009;179606008 |
| N2A | None | None | chr2:None | chr2:None |
| N2B | 3621 | 11086;11087;11088 | chr2:178741283;178741282;178741281 | chr2:179606010;179606009;179606008 |
| Novex-1 | 3746 | 11461;11462;11463 | chr2:178741283;178741282;178741281 | chr2:179606010;179606009;179606008 |
| Novex-2 | 3813 | 11662;11663;11664 | chr2:178741283;178741282;178741281 | chr2:179606010;179606009;179606008 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/F | rs776443623  |
-0.505 | None | N | 0.187 | 0.131 | None | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| Y/F | rs776443623 |
-0.505 | None | N | 0.187 | 0.131 | None | gnomAD-4.0.0 | 1.59114E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85789E-06 | 0 | 0 |
| Y/H | rs1263949163 |
-1.667 | None | N | 0.285 | 0.122 | None | gnomAD-2.1.1 | 3.18E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 6.41849E-04 | None | 0 | None | 0 | 0 | 0 |
| Y/H | rs1263949163 |
-1.667 | None | N | 0.285 | 0.122 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.92456E-04 | None | 0 | 0 | 0 | 0 | 0 |
| Y/H | rs1263949163 |
-1.667 | None | N | 0.285 | 0.122 | None | gnomAD-4.0.0 | 2.56182E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.42389E-05 | None | 0 | 0 | 0 | 1.33998E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.7283 | likely_pathogenic | 0.6683 | pathogenic | -2.577 | Highly Destabilizing | 0.016 | N | 0.393 | neutral | None | None | None | None | N |
| Y/C | 0.1488 | likely_benign | 0.1391 | benign | -1.912 | Destabilizing | None | N | 0.328 | neutral | N | 0.514303215 | None | None | N |
| Y/D | 0.6378 | likely_pathogenic | 0.5714 | pathogenic | -2.2 | Highly Destabilizing | 0.055 | N | 0.591 | neutral | D | 0.558899366 | None | None | N |
| Y/E | 0.8633 | likely_pathogenic | 0.7972 | pathogenic | -1.989 | Destabilizing | 0.038 | N | 0.511 | neutral | None | None | None | None | N |
| Y/F | 0.1996 | likely_benign | 0.1708 | benign | -0.919 | Destabilizing | None | N | 0.187 | neutral | N | 0.463611292 | None | None | N |
| Y/G | 0.6602 | likely_pathogenic | 0.5996 | pathogenic | -3.012 | Highly Destabilizing | 0.072 | N | 0.53 | neutral | None | None | None | None | N |
| Y/H | 0.222 | likely_benign | 0.1724 | benign | -1.757 | Destabilizing | None | N | 0.285 | neutral | N | 0.506421267 | None | None | N |
| Y/I | 0.7818 | likely_pathogenic | 0.7325 | pathogenic | -1.167 | Destabilizing | 0.038 | N | 0.517 | neutral | None | None | None | None | N |
| Y/K | 0.8031 | likely_pathogenic | 0.7078 | pathogenic | -1.794 | Destabilizing | 0.038 | N | 0.495 | neutral | None | None | None | None | N |
| Y/L | 0.6806 | likely_pathogenic | 0.6427 | pathogenic | -1.167 | Destabilizing | 0.016 | N | 0.434 | neutral | None | None | None | None | N |
| Y/M | 0.8591 | likely_pathogenic | 0.8185 | pathogenic | -1.199 | Destabilizing | 0.356 | N | 0.519 | neutral | None | None | None | None | N |
| Y/N | 0.3338 | likely_benign | 0.2985 | benign | -2.475 | Highly Destabilizing | 0.029 | N | 0.545 | neutral | D | 0.600927703 | None | None | N |
| Y/P | 0.9676 | likely_pathogenic | 0.9531 | pathogenic | -1.647 | Destabilizing | 0.356 | N | 0.573 | neutral | None | None | None | None | N |
| Y/Q | 0.6917 | likely_pathogenic | 0.587 | pathogenic | -2.171 | Highly Destabilizing | 0.214 | N | 0.541 | neutral | None | None | None | None | N |
| Y/R | 0.586 | likely_pathogenic | 0.4585 | ambiguous | -1.705 | Destabilizing | None | N | 0.31 | neutral | None | None | None | None | N |
| Y/S | 0.3459 | ambiguous | 0.3141 | benign | -3.028 | Highly Destabilizing | 0.055 | N | 0.517 | neutral | D | 0.540731517 | None | None | N |
| Y/T | 0.6644 | likely_pathogenic | 0.5902 | pathogenic | -2.685 | Highly Destabilizing | 0.072 | N | 0.513 | neutral | None | None | None | None | N |
| Y/V | 0.6611 | likely_pathogenic | 0.6024 | pathogenic | -1.647 | Destabilizing | 0.038 | N | 0.485 | neutral | None | None | None | None | N |
| Y/W | 0.6282 | likely_pathogenic | 0.5448 | ambiguous | -0.267 | Destabilizing | 0.356 | N | 0.49 | 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.