Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25620 | 77083;77084;77085 | chr2:178569274;178569273;178569272 | chr2:179434001;179434000;179433999 |
| N2AB | 23979 | 72160;72161;72162 | chr2:178569274;178569273;178569272 | chr2:179434001;179434000;179433999 |
| N2A | 23052 | 69379;69380;69381 | chr2:178569274;178569273;178569272 | chr2:179434001;179434000;179433999 |
| N2B | 16555 | 49888;49889;49890 | chr2:178569274;178569273;178569272 | chr2:179434001;179434000;179433999 |
| Novex-1 | 16680 | 50263;50264;50265 | chr2:178569274;178569273;178569272 | chr2:179434001;179434000;179433999 |
| Novex-2 | 16747 | 50464;50465;50466 | chr2:178569274;178569273;178569272 | chr2:179434001;179434000;179433999 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/V | rs773656560  |
-1.09 | 0.078 | N | 0.351 | 0.07 | None | gnomAD-2.1.1 | 2.04E-05 | None | None | None | None | N | None | 0 | 2.93E-05 | None | 0 | 0 | None | 0 | None | 4.71E-05 | 2.69E-05 | 0 |
| I/V | rs773656560 |
-1.09 | 0.078 | N | 0.351 | 0.07 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 3.16456E-03 | 1.47E-05 | 2.06954E-04 | 0 |
| I/V | rs773656560 |
-1.09 | 0.078 | N | 0.351 | 0.07 | None | gnomAD-4.0.0 | 2.86013E-05 | None | None | None | None | N | None | 0 | 1.67949E-05 | None | 0 | 0 | None | 1.56612E-05 | 3.32116E-04 | 2.54955E-05 | 9.9723E-05 | 4.82594E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.851 | likely_pathogenic | 0.8787 | pathogenic | -2.502 | Highly Destabilizing | 0.543 | D | 0.617 | neutral | None | None | None | None | N |
| I/C | 0.8627 | likely_pathogenic | 0.8874 | pathogenic | -1.779 | Destabilizing | 0.984 | D | 0.775 | deleterious | None | None | None | None | N |
| I/D | 0.9992 | likely_pathogenic | 0.9993 | pathogenic | -2.997 | Highly Destabilizing | 0.984 | D | 0.827 | deleterious | None | None | None | None | N |
| I/E | 0.9976 | likely_pathogenic | 0.9979 | pathogenic | -2.656 | Highly Destabilizing | 0.953 | D | 0.8 | deleterious | None | None | None | None | N |
| I/F | 0.3485 | ambiguous | 0.3714 | ambiguous | -1.508 | Destabilizing | 0.684 | D | 0.617 | neutral | N | 0.483623689 | None | None | N |
| I/G | 0.9872 | likely_pathogenic | 0.9896 | pathogenic | -3.143 | Highly Destabilizing | 0.953 | D | 0.792 | deleterious | None | None | None | None | N |
| I/H | 0.9941 | likely_pathogenic | 0.9952 | pathogenic | -2.967 | Highly Destabilizing | 0.996 | D | 0.855 | deleterious | None | None | None | None | N |
| I/K | 0.9954 | likely_pathogenic | 0.9961 | pathogenic | -1.845 | Destabilizing | 0.854 | D | 0.791 | deleterious | None | None | None | None | N |
| I/L | 0.0684 | likely_benign | 0.0706 | benign | -0.581 | Destabilizing | 0.001 | N | 0.191 | neutral | N | 0.34717128 | None | None | N |
| I/M | 0.1341 | likely_benign | 0.1448 | benign | -0.796 | Destabilizing | 0.884 | D | 0.641 | neutral | D | 0.523444691 | None | None | N |
| I/N | 0.9904 | likely_pathogenic | 0.9913 | pathogenic | -2.573 | Highly Destabilizing | 0.979 | D | 0.84 | deleterious | N | 0.511389183 | None | None | N |
| I/P | 0.9965 | likely_pathogenic | 0.9972 | pathogenic | -1.211 | Destabilizing | 0.984 | D | 0.838 | deleterious | None | None | None | None | N |
| I/Q | 0.9933 | likely_pathogenic | 0.9944 | pathogenic | -2.152 | Highly Destabilizing | 0.984 | D | 0.845 | deleterious | None | None | None | None | N |
| I/R | 0.9921 | likely_pathogenic | 0.9934 | pathogenic | -2.066 | Highly Destabilizing | 0.953 | D | 0.823 | deleterious | None | None | None | None | N |
| I/S | 0.9756 | likely_pathogenic | 0.9783 | pathogenic | -3.177 | Highly Destabilizing | 0.815 | D | 0.729 | prob.delet. | N | 0.499868293 | None | None | N |
| I/T | 0.9367 | likely_pathogenic | 0.9445 | pathogenic | -2.652 | Highly Destabilizing | 0.684 | D | 0.682 | prob.neutral | N | 0.511135693 | None | None | N |
| I/V | 0.0833 | likely_benign | 0.0866 | benign | -1.211 | Destabilizing | 0.078 | N | 0.351 | neutral | N | 0.449882721 | None | None | N |
| I/W | 0.9841 | likely_pathogenic | 0.9869 | pathogenic | -1.89 | Destabilizing | 0.996 | D | 0.851 | deleterious | None | None | None | None | N |
| I/Y | 0.9476 | likely_pathogenic | 0.955 | pathogenic | -1.633 | Destabilizing | 0.953 | D | 0.73 | 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.