Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19148 | 57667;57668;57669 | chr2:178597640;178597639;178597638 | chr2:179462367;179462366;179462365 |
| N2AB | 17507 | 52744;52745;52746 | chr2:178597640;178597639;178597638 | chr2:179462367;179462366;179462365 |
| N2A | 16580 | 49963;49964;49965 | chr2:178597640;178597639;178597638 | chr2:179462367;179462366;179462365 |
| N2B | 10083 | 30472;30473;30474 | chr2:178597640;178597639;178597638 | chr2:179462367;179462366;179462365 |
| Novex-1 | 10208 | 30847;30848;30849 | chr2:178597640;178597639;178597638 | chr2:179462367;179462366;179462365 |
| Novex-2 | 10275 | 31048;31049;31050 | chr2:178597640;178597639;178597638 | chr2:179462367;179462366;179462365 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/L | None | None | 0.001 | N | 0.224 | 0.102 | 0.154104182512 | gnomAD-4.0.0 | 2.05325E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69892E-06 | 0 | 0 |
| M/T | rs751101760  |
None | 0.6 | N | 0.595 | 0.302 | 0.60311569301 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.625E-06 | 0 | 0 |
| M/V | rs188185141 |
-0.463 | 0.065 | N | 0.425 | 0.144 | None | gnomAD-2.1.1 | 4.97484E-04 | None | None | None | None | N | None | 8.27E-05 | 5.67E-05 | None | 0 | 4.13522E-04 | None | 0 | None | 4.79655E-04 | 8.86094E-04 | 2.81294E-04 |
| M/V | rs188185141 |
-0.463 | 0.065 | N | 0.425 | 0.144 | None | gnomAD-3.1.2 | 3.94612E-04 | None | None | None | None | N | None | 1.20697E-04 | 6.55E-05 | 0 | 0 | 5.83658E-04 | None | 1.88288E-04 | 0 | 7.0609E-04 | 0 | 4.78011E-04 |
| M/V | rs188185141 |
-0.463 | 0.065 | N | 0.425 | 0.144 | None | 1000 genomes | 3.99361E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 1E-03 | 1E-03 | None | None | None | 0 | None |
| M/V | rs188185141 |
-0.463 | 0.065 | N | 0.425 | 0.144 | None | gnomAD-4.0.0 | 6.66352E-04 | None | None | None | None | N | None | 1.60009E-04 | 5.003E-05 | None | 0 | 2.46118E-04 | None | 4.37418E-04 | 0 | 8.47798E-04 | 0 | 3.36226E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.8342 | likely_pathogenic | 0.8918 | pathogenic | -1.645 | Destabilizing | 0.495 | N | 0.571 | neutral | None | None | None | None | N |
| M/C | 0.8842 | likely_pathogenic | 0.9048 | pathogenic | -1.934 | Destabilizing | 0.981 | D | 0.711 | prob.delet. | None | None | None | None | N |
| M/D | 0.9994 | likely_pathogenic | 0.9997 | pathogenic | -1.875 | Destabilizing | 0.981 | D | 0.759 | deleterious | None | None | None | None | N |
| M/E | 0.9945 | likely_pathogenic | 0.9968 | pathogenic | -1.59 | Destabilizing | 0.936 | D | 0.704 | prob.neutral | None | None | None | None | N |
| M/F | 0.5838 | likely_pathogenic | 0.6621 | pathogenic | -0.355 | Destabilizing | 0.704 | D | 0.573 | neutral | None | None | None | None | N |
| M/G | 0.9842 | likely_pathogenic | 0.9904 | pathogenic | -2.167 | Highly Destabilizing | 0.936 | D | 0.707 | prob.neutral | None | None | None | None | N |
| M/H | 0.992 | likely_pathogenic | 0.9958 | pathogenic | -2.16 | Highly Destabilizing | 0.981 | D | 0.758 | deleterious | None | None | None | None | N |
| M/I | 0.404 | ambiguous | 0.4761 | ambiguous | -0.128 | Destabilizing | 0.01 | N | 0.285 | neutral | N | 0.387404537 | None | None | N |
| M/K | 0.9796 | likely_pathogenic | 0.9896 | pathogenic | -0.94 | Destabilizing | 0.784 | D | 0.623 | neutral | N | 0.484299152 | None | None | N |
| M/L | 0.0965 | likely_benign | 0.1027 | benign | -0.128 | Destabilizing | 0.001 | N | 0.224 | neutral | N | 0.256809408 | None | None | N |
| M/N | 0.9944 | likely_pathogenic | 0.997 | pathogenic | -1.54 | Destabilizing | 0.981 | D | 0.729 | prob.delet. | None | None | None | None | N |
| M/P | 0.998 | likely_pathogenic | 0.9989 | pathogenic | -0.617 | Destabilizing | 0.981 | D | 0.734 | prob.delet. | None | None | None | None | N |
| M/Q | 0.9758 | likely_pathogenic | 0.9851 | pathogenic | -1.077 | Destabilizing | 0.981 | D | 0.636 | neutral | None | None | None | None | N |
| M/R | 0.9771 | likely_pathogenic | 0.9884 | pathogenic | -1.386 | Destabilizing | 0.784 | D | 0.699 | prob.neutral | N | 0.484299152 | None | None | N |
| M/S | 0.9789 | likely_pathogenic | 0.9893 | pathogenic | -1.981 | Destabilizing | 0.828 | D | 0.612 | neutral | None | None | None | None | N |
| M/T | 0.9076 | likely_pathogenic | 0.952 | pathogenic | -1.551 | Destabilizing | 0.6 | D | 0.595 | neutral | N | 0.484299152 | None | None | N |
| M/V | 0.1093 | likely_benign | 0.1358 | benign | -0.617 | Destabilizing | 0.065 | N | 0.425 | neutral | N | 0.411974907 | None | None | N |
| M/W | 0.9779 | likely_pathogenic | 0.9889 | pathogenic | -0.803 | Destabilizing | 0.995 | D | 0.714 | prob.delet. | None | None | None | None | N |
| M/Y | 0.9644 | likely_pathogenic | 0.9802 | pathogenic | -0.681 | Destabilizing | 0.944 | D | 0.701 | prob.neutral | 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.