Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21640 | 65143;65144;65145 | chr2:178584723;178584722;178584721 | chr2:179449450;179449449;179449448 |
| N2AB | 19999 | 60220;60221;60222 | chr2:178584723;178584722;178584721 | chr2:179449450;179449449;179449448 |
| N2A | 19072 | 57439;57440;57441 | chr2:178584723;178584722;178584721 | chr2:179449450;179449449;179449448 |
| N2B | 12575 | 37948;37949;37950 | chr2:178584723;178584722;178584721 | chr2:179449450;179449449;179449448 |
| Novex-1 | 12700 | 38323;38324;38325 | chr2:178584723;178584722;178584721 | chr2:179449450;179449449;179449448 |
| Novex-2 | 12767 | 38524;38525;38526 | chr2:178584723;178584722;178584721 | chr2:179449450;179449449;179449448 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/S | rs1475736042  |
None | 0.997 | N | 0.637 | 0.321 | 0.629863665223 | gnomAD-4.0.0 | 6.84326E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.52003E-05 | None | 0 | 0 | 0 | 0 | 0 |
| F/Y | rs1475736042 |
-0.461 | 0.4 | N | 0.287 | 0.202 | 0.206339911435 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | I | None | 0 | 1.15929E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| F/Y | rs1475736042 |
-0.461 | 0.4 | N | 0.287 | 0.202 | 0.206339911435 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| F/Y | rs1475736042 |
-0.461 | 0.4 | N | 0.287 | 0.202 | 0.206339911435 | gnomAD-4.0.0 | 4.33875E-06 | None | None | None | None | I | None | 0 | 1.0003E-04 | None | 0 | 0 | None | 0 | 0 | 8.47758E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.9709 | likely_pathogenic | 0.9656 | pathogenic | -0.99 | Destabilizing | 0.993 | D | 0.62 | neutral | None | None | None | None | I |
| F/C | 0.8501 | likely_pathogenic | 0.7879 | pathogenic | -0.354 | Destabilizing | 1.0 | D | 0.72 | prob.delet. | N | 0.474093306 | None | None | I |
| F/D | 0.9906 | likely_pathogenic | 0.9899 | pathogenic | 0.928 | Stabilizing | 0.999 | D | 0.725 | prob.delet. | None | None | None | None | I |
| F/E | 0.9918 | likely_pathogenic | 0.9908 | pathogenic | 0.91 | Stabilizing | 0.999 | D | 0.729 | prob.delet. | None | None | None | None | I |
| F/G | 0.9861 | likely_pathogenic | 0.9862 | pathogenic | -1.184 | Destabilizing | 0.999 | D | 0.665 | neutral | None | None | None | None | I |
| F/H | 0.8702 | likely_pathogenic | 0.8342 | pathogenic | 0.203 | Stabilizing | 0.998 | D | 0.57 | neutral | None | None | None | None | I |
| F/I | 0.8986 | likely_pathogenic | 0.8597 | pathogenic | -0.498 | Destabilizing | 0.961 | D | 0.472 | neutral | N | 0.429513023 | None | None | I |
| F/K | 0.9899 | likely_pathogenic | 0.988 | pathogenic | -0.033 | Destabilizing | 0.998 | D | 0.724 | prob.delet. | None | None | None | None | I |
| F/L | 0.9865 | likely_pathogenic | 0.9833 | pathogenic | -0.498 | Destabilizing | 0.135 | N | 0.201 | neutral | N | 0.485155662 | None | None | I |
| F/M | 0.9098 | likely_pathogenic | 0.9033 | pathogenic | -0.373 | Destabilizing | 0.996 | D | 0.507 | neutral | None | None | None | None | I |
| F/N | 0.9488 | likely_pathogenic | 0.9355 | pathogenic | 0.029 | Stabilizing | 0.999 | D | 0.729 | prob.delet. | None | None | None | None | I |
| F/P | 0.9994 | likely_pathogenic | 0.9993 | pathogenic | -0.642 | Destabilizing | 0.999 | D | 0.726 | prob.delet. | None | None | None | None | I |
| F/Q | 0.975 | likely_pathogenic | 0.9715 | pathogenic | -0.034 | Destabilizing | 0.999 | D | 0.724 | prob.delet. | None | None | None | None | I |
| F/R | 0.9734 | likely_pathogenic | 0.9697 | pathogenic | 0.431 | Stabilizing | 0.999 | D | 0.727 | prob.delet. | None | None | None | None | I |
| F/S | 0.951 | likely_pathogenic | 0.938 | pathogenic | -0.709 | Destabilizing | 0.997 | D | 0.637 | neutral | N | 0.519921597 | None | None | I |
| F/T | 0.9748 | likely_pathogenic | 0.9666 | pathogenic | -0.635 | Destabilizing | 0.998 | D | 0.635 | neutral | None | None | None | None | I |
| F/V | 0.8867 | likely_pathogenic | 0.8435 | pathogenic | -0.642 | Destabilizing | 0.961 | D | 0.547 | neutral | N | 0.434937485 | None | None | I |
| F/W | 0.6858 | likely_pathogenic | 0.6418 | pathogenic | -0.26 | Destabilizing | 1.0 | D | 0.519 | neutral | None | None | None | None | I |
| F/Y | 0.2011 | likely_benign | 0.1656 | benign | -0.234 | Destabilizing | 0.4 | N | 0.287 | neutral | N | 0.403174571 | 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.