Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25685 | 77278;77279;77280 | chr2:178569079;178569078;178569077 | chr2:179433806;179433805;179433804 |
| N2AB | 24044 | 72355;72356;72357 | chr2:178569079;178569078;178569077 | chr2:179433806;179433805;179433804 |
| N2A | 23117 | 69574;69575;69576 | chr2:178569079;178569078;178569077 | chr2:179433806;179433805;179433804 |
| N2B | 16620 | 50083;50084;50085 | chr2:178569079;178569078;178569077 | chr2:179433806;179433805;179433804 |
| Novex-1 | 16745 | 50458;50459;50460 | chr2:178569079;178569078;178569077 | chr2:179433806;179433805;179433804 |
| Novex-2 | 16812 | 50659;50660;50661 | chr2:178569079;178569078;178569077 | chr2:179433806;179433805;179433804 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/F | rs1707149968  |
None | 0.755 | N | 0.64 | 0.216 | 0.513958542087 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 4.79386E-04 |
| L/F | rs1707149968 |
None | 0.755 | N | 0.64 | 0.216 | 0.513958542087 | gnomAD-4.0.0 | 2.47948E-06 | None | None | None | None | I | None | 2.67101E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.20359E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.2095 | likely_benign | 0.2676 | benign | -1.167 | Destabilizing | 0.594 | D | 0.593 | neutral | None | None | None | None | I |
| L/C | 0.5084 | ambiguous | 0.5801 | pathogenic | -0.709 | Destabilizing | 0.987 | D | 0.707 | prob.neutral | None | None | None | None | I |
| L/D | 0.5233 | ambiguous | 0.617 | pathogenic | -0.518 | Destabilizing | 0.837 | D | 0.661 | neutral | None | None | None | None | I |
| L/E | 0.2394 | likely_benign | 0.3107 | benign | -0.585 | Destabilizing | 0.015 | N | 0.444 | neutral | None | None | None | None | I |
| L/F | 0.1344 | likely_benign | 0.1633 | benign | -0.988 | Destabilizing | 0.755 | D | 0.64 | neutral | N | 0.477935242 | None | None | I |
| L/G | 0.5192 | ambiguous | 0.61 | pathogenic | -1.397 | Destabilizing | 0.911 | D | 0.676 | prob.neutral | None | None | None | None | I |
| L/H | 0.2397 | likely_benign | 0.2983 | benign | -0.611 | Destabilizing | 0.961 | D | 0.752 | deleterious | N | 0.473833866 | None | None | I |
| L/I | 0.0833 | likely_benign | 0.0899 | benign | -0.656 | Destabilizing | 0.011 | N | 0.515 | neutral | N | 0.510800681 | None | None | I |
| L/K | 0.2845 | likely_benign | 0.3522 | ambiguous | -0.646 | Destabilizing | 0.041 | N | 0.617 | neutral | None | None | None | None | I |
| L/M | 0.1038 | likely_benign | 0.1155 | benign | -0.474 | Destabilizing | 0.551 | D | 0.641 | neutral | None | None | None | None | I |
| L/N | 0.3011 | likely_benign | 0.362 | ambiguous | -0.39 | Destabilizing | 0.911 | D | 0.747 | deleterious | None | None | None | None | I |
| L/P | 0.3217 | likely_benign | 0.3943 | ambiguous | -0.793 | Destabilizing | 0.94 | D | 0.748 | deleterious | N | 0.442996821 | None | None | I |
| L/Q | 0.1343 | likely_benign | 0.1755 | benign | -0.648 | Destabilizing | 0.036 | N | 0.433 | neutral | None | None | None | None | I |
| L/R | 0.2688 | likely_benign | 0.351 | ambiguous | -0.02 | Destabilizing | 0.607 | D | 0.725 | prob.delet. | N | 0.49715938 | None | None | I |
| L/S | 0.2125 | likely_benign | 0.2765 | benign | -0.934 | Destabilizing | 0.594 | D | 0.627 | neutral | None | None | None | None | I |
| L/T | 0.2034 | likely_benign | 0.2514 | benign | -0.892 | Destabilizing | 0.468 | N | 0.616 | neutral | None | None | None | None | I |
| L/V | 0.0842 | likely_benign | 0.0958 | benign | -0.793 | Destabilizing | None | N | 0.291 | neutral | N | 0.448424071 | None | None | I |
| L/W | 0.3385 | likely_benign | 0.4016 | ambiguous | -0.977 | Destabilizing | 0.997 | D | 0.776 | deleterious | None | None | None | None | I |
| L/Y | 0.3284 | likely_benign | 0.3895 | ambiguous | -0.751 | Destabilizing | 0.493 | N | 0.713 | prob.delet. | None | None | None | None | I |
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.