Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23196 | 69811;69812;69813 | chr2:178576658;178576657;178576656 | chr2:179441385;179441384;179441383 |
| N2AB | 21555 | 64888;64889;64890 | chr2:178576658;178576657;178576656 | chr2:179441385;179441384;179441383 |
| N2A | 20628 | 62107;62108;62109 | chr2:178576658;178576657;178576656 | chr2:179441385;179441384;179441383 |
| N2B | 14131 | 42616;42617;42618 | chr2:178576658;178576657;178576656 | chr2:179441385;179441384;179441383 |
| Novex-1 | 14256 | 42991;42992;42993 | chr2:178576658;178576657;178576656 | chr2:179441385;179441384;179441383 |
| Novex-2 | 14323 | 43192;43193;43194 | chr2:178576658;178576657;178576656 | chr2:179441385;179441384;179441383 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | None | None | 0.979 | N | 0.456 | 0.175 | 0.170165803431 | gnomAD-4.0.0 | 1.59161E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85922E-06 | 0 | 0 |
| D/N | rs1162141375  |
-0.243 | 0.999 | N | 0.665 | 0.29 | 0.219573609325 | gnomAD-2.1.1 | 8.04E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| D/N | rs1162141375 |
-0.243 | 0.999 | N | 0.665 | 0.29 | 0.219573609325 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/N | rs1162141375 |
-0.243 | 0.999 | N | 0.665 | 0.29 | 0.219573609325 | gnomAD-4.0.0 | 6.81733E-06 | None | None | None | None | N | None | 1.33351E-05 | 3.33378E-05 | None | 0 | 0 | None | 0 | 0 | 4.23865E-06 | 2.19631E-05 | 1.60092E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.5908 | likely_pathogenic | 0.5908 | pathogenic | 0.07 | Stabilizing | 0.988 | D | 0.649 | neutral | N | 0.486291812 | None | None | N |
| D/C | 0.9222 | likely_pathogenic | 0.929 | pathogenic | -0.202 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | None | N |
| D/E | 0.3908 | ambiguous | 0.379 | ambiguous | -0.379 | Destabilizing | 0.979 | D | 0.456 | neutral | N | 0.418970742 | None | None | N |
| D/F | 0.9047 | likely_pathogenic | 0.9132 | pathogenic | 0.536 | Stabilizing | 0.982 | D | 0.749 | deleterious | None | None | None | None | N |
| D/G | 0.5932 | likely_pathogenic | 0.5903 | pathogenic | -0.196 | Destabilizing | 0.979 | D | 0.697 | prob.neutral | N | 0.470207639 | None | None | N |
| D/H | 0.7554 | likely_pathogenic | 0.7714 | pathogenic | 0.93 | Stabilizing | 0.999 | D | 0.732 | prob.delet. | N | 0.515190567 | None | None | N |
| D/I | 0.8486 | likely_pathogenic | 0.8566 | pathogenic | 0.741 | Stabilizing | 0.991 | D | 0.751 | deleterious | None | None | None | None | N |
| D/K | 0.889 | likely_pathogenic | 0.8955 | pathogenic | 0.442 | Stabilizing | 0.995 | D | 0.767 | deleterious | None | None | None | None | N |
| D/L | 0.8103 | likely_pathogenic | 0.8153 | pathogenic | 0.741 | Stabilizing | 0.982 | D | 0.745 | deleterious | None | None | None | None | N |
| D/M | 0.9189 | likely_pathogenic | 0.9211 | pathogenic | 0.529 | Stabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | N |
| D/N | 0.3513 | ambiguous | 0.3647 | ambiguous | -0.292 | Destabilizing | 0.999 | D | 0.665 | neutral | N | 0.503472064 | None | None | N |
| D/P | 0.9666 | likely_pathogenic | 0.9648 | pathogenic | 0.542 | Stabilizing | 0.998 | D | 0.751 | deleterious | None | None | None | None | N |
| D/Q | 0.7872 | likely_pathogenic | 0.7967 | pathogenic | -0.161 | Destabilizing | 0.995 | D | 0.685 | prob.neutral | None | None | None | None | N |
| D/R | 0.8781 | likely_pathogenic | 0.8864 | pathogenic | 0.806 | Stabilizing | 0.995 | D | 0.747 | deleterious | None | None | None | None | N |
| D/S | 0.3831 | ambiguous | 0.391 | ambiguous | -0.366 | Destabilizing | 0.995 | D | 0.672 | neutral | None | None | None | None | N |
| D/T | 0.6914 | likely_pathogenic | 0.6917 | pathogenic | -0.123 | Destabilizing | 0.995 | D | 0.763 | deleterious | None | None | None | None | N |
| D/V | 0.6654 | likely_pathogenic | 0.6827 | pathogenic | 0.542 | Stabilizing | 0.988 | D | 0.749 | deleterious | N | 0.487619964 | None | None | N |
| D/W | 0.9829 | likely_pathogenic | 0.9851 | pathogenic | 0.71 | Stabilizing | 0.999 | D | 0.719 | prob.delet. | None | None | None | None | N |
| D/Y | 0.6363 | likely_pathogenic | 0.6661 | pathogenic | 0.817 | Stabilizing | 0.296 | N | 0.446 | neutral | N | 0.467734707 | 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.