Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27014 | 81265;81266;81267 | chr2:178565092;178565091;178565090 | chr2:179429819;179429818;179429817 |
| N2AB | 25373 | 76342;76343;76344 | chr2:178565092;178565091;178565090 | chr2:179429819;179429818;179429817 |
| N2A | 24446 | 73561;73562;73563 | chr2:178565092;178565091;178565090 | chr2:179429819;179429818;179429817 |
| N2B | 17949 | 54070;54071;54072 | chr2:178565092;178565091;178565090 | chr2:179429819;179429818;179429817 |
| Novex-1 | 18074 | 54445;54446;54447 | chr2:178565092;178565091;178565090 | chr2:179429819;179429818;179429817 |
| Novex-2 | 18141 | 54646;54647;54648 | chr2:178565092;178565091;178565090 | chr2:179429819;179429818;179429817 |
| 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 | rs1468937743  |
None | 0.117 | N | 0.295 | 0.089 | 0.223146558224 | gnomAD-4.0.0 | 6.84284E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.9956E-07 | 0 | 0 |
| D/N | rs1195586703 |
-0.83 | 0.993 | N | 0.617 | 0.428 | 0.371903410333 | 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 |
| D/N | rs1195586703 |
-0.83 | 0.993 | N | 0.617 | 0.428 | 0.371903410333 | gnomAD-4.0.0 | 1.59167E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85919E-06 | 0 | 0 |
| D/V | rs954420443 |
None | 0.997 | N | 0.821 | 0.617 | 0.564579235405 | gnomAD-4.0.0 | 1.59169E-06 | None | None | None | None | N | None | 0 | 2.28686E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.5977 | likely_pathogenic | 0.4656 | ambiguous | -0.647 | Destabilizing | 0.993 | D | 0.661 | neutral | N | 0.479002107 | None | None | N |
| D/C | 0.82 | likely_pathogenic | 0.7508 | pathogenic | -0.236 | Destabilizing | 1.0 | D | 0.766 | deleterious | None | None | None | None | N |
| D/E | 0.2896 | likely_benign | 0.2092 | benign | -0.822 | Destabilizing | 0.117 | N | 0.295 | neutral | N | 0.432859972 | None | None | N |
| D/F | 0.9594 | likely_pathogenic | 0.9263 | pathogenic | -0.633 | Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | N |
| D/G | 0.7362 | likely_pathogenic | 0.6275 | pathogenic | -0.954 | Destabilizing | 0.977 | D | 0.668 | neutral | N | 0.47902856 | None | None | N |
| D/H | 0.8182 | likely_pathogenic | 0.7367 | pathogenic | -0.972 | Destabilizing | 0.999 | D | 0.775 | deleterious | D | 0.524618366 | None | None | N |
| D/I | 0.8286 | likely_pathogenic | 0.7289 | pathogenic | 0.15 | Stabilizing | 0.998 | D | 0.823 | deleterious | None | None | None | None | N |
| D/K | 0.9025 | likely_pathogenic | 0.8422 | pathogenic | -0.442 | Destabilizing | 0.99 | D | 0.668 | neutral | None | None | None | None | N |
| D/L | 0.8075 | likely_pathogenic | 0.7089 | pathogenic | 0.15 | Stabilizing | 0.995 | D | 0.819 | deleterious | None | None | None | None | N |
| D/M | 0.9158 | likely_pathogenic | 0.852 | pathogenic | 0.662 | Stabilizing | 1.0 | D | 0.778 | deleterious | None | None | None | None | N |
| D/N | 0.3188 | likely_benign | 0.2439 | benign | -0.747 | Destabilizing | 0.993 | D | 0.617 | neutral | N | 0.482787542 | None | None | N |
| D/P | 0.9609 | likely_pathogenic | 0.9287 | pathogenic | -0.091 | Destabilizing | 0.998 | D | 0.808 | deleterious | None | None | None | None | N |
| D/Q | 0.8228 | likely_pathogenic | 0.7204 | pathogenic | -0.663 | Destabilizing | 0.99 | D | 0.724 | prob.delet. | None | None | None | None | N |
| D/R | 0.9335 | likely_pathogenic | 0.896 | pathogenic | -0.383 | Destabilizing | 0.995 | D | 0.795 | deleterious | None | None | None | None | N |
| D/S | 0.5483 | ambiguous | 0.4279 | ambiguous | -0.996 | Destabilizing | 0.983 | D | 0.578 | neutral | None | None | None | None | N |
| D/T | 0.7859 | likely_pathogenic | 0.6746 | pathogenic | -0.749 | Destabilizing | 0.995 | D | 0.768 | deleterious | None | None | None | None | N |
| D/V | 0.6594 | likely_pathogenic | 0.5278 | ambiguous | -0.091 | Destabilizing | 0.997 | D | 0.821 | deleterious | N | 0.492689044 | None | None | N |
| D/W | 0.9913 | likely_pathogenic | 0.9853 | pathogenic | -0.548 | Destabilizing | 1.0 | D | 0.777 | deleterious | None | None | None | None | N |
| D/Y | 0.7576 | likely_pathogenic | 0.665 | pathogenic | -0.418 | Destabilizing | 1.0 | D | 0.797 | deleterious | D | 0.525632324 | 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.