Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30375 | 91348;91349;91350 | chr2:178551777;178551776;178551775 | chr2:179416504;179416503;179416502 |
| N2AB | 28734 | 86425;86426;86427 | chr2:178551777;178551776;178551775 | chr2:179416504;179416503;179416502 |
| N2A | 27807 | 83644;83645;83646 | chr2:178551777;178551776;178551775 | chr2:179416504;179416503;179416502 |
| N2B | 21310 | 64153;64154;64155 | chr2:178551777;178551776;178551775 | chr2:179416504;179416503;179416502 |
| Novex-1 | 21435 | 64528;64529;64530 | chr2:178551777;178551776;178551775 | chr2:179416504;179416503;179416502 |
| Novex-2 | 21502 | 64729;64730;64731 | chr2:178551777;178551776;178551775 | chr2:179416504;179416503;179416502 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/I | rs775683499  |
0.052 | 1.0 | N | 0.772 | 0.506 | 0.527660502957 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| N/I | rs775683499 |
0.052 | 1.0 | N | 0.772 | 0.506 | 0.527660502957 | gnomAD-4.0.0 | 1.59115E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85804E-06 | 0 | 0 |
| N/K | None | None | 1.0 | N | 0.742 | 0.376 | 0.246773566709 | gnomAD-4.0.0 | 6.84192E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99452E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.6442 | likely_pathogenic | 0.6161 | pathogenic | -0.977 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | N |
| N/C | 0.4326 | ambiguous | 0.3785 | ambiguous | -0.079 | Destabilizing | 1.0 | D | 0.756 | deleterious | None | None | None | None | N |
| N/D | 0.6524 | likely_pathogenic | 0.6689 | pathogenic | -0.976 | Destabilizing | 0.999 | D | 0.645 | neutral | N | 0.474370979 | None | None | N |
| N/E | 0.9444 | likely_pathogenic | 0.9412 | pathogenic | -0.783 | Destabilizing | 0.999 | D | 0.719 | prob.delet. | None | None | None | None | N |
| N/F | 0.9465 | likely_pathogenic | 0.9441 | pathogenic | -0.522 | Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | N |
| N/G | 0.604 | likely_pathogenic | 0.5575 | ambiguous | -1.393 | Destabilizing | 0.999 | D | 0.591 | neutral | None | None | None | None | N |
| N/H | 0.5171 | ambiguous | 0.4911 | ambiguous | -0.999 | Destabilizing | 1.0 | D | 0.763 | deleterious | N | 0.514673279 | None | None | N |
| N/I | 0.7383 | likely_pathogenic | 0.7179 | pathogenic | 0.126 | Stabilizing | 1.0 | D | 0.772 | deleterious | N | 0.480055745 | None | None | N |
| N/K | 0.9644 | likely_pathogenic | 0.9613 | pathogenic | -0.215 | Destabilizing | 1.0 | D | 0.742 | deleterious | N | 0.483334201 | None | None | N |
| N/L | 0.7328 | likely_pathogenic | 0.7121 | pathogenic | 0.126 | Stabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | N |
| N/M | 0.751 | likely_pathogenic | 0.7406 | pathogenic | 0.475 | Stabilizing | 1.0 | D | 0.762 | deleterious | None | None | None | None | N |
| N/P | 0.9388 | likely_pathogenic | 0.9364 | pathogenic | -0.212 | Destabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | N |
| N/Q | 0.8921 | likely_pathogenic | 0.8852 | pathogenic | -0.762 | Destabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | N |
| N/R | 0.9518 | likely_pathogenic | 0.9479 | pathogenic | -0.439 | Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | N |
| N/S | 0.1061 | likely_benign | 0.0983 | benign | -1.089 | Destabilizing | 0.999 | D | 0.605 | neutral | N | 0.485675737 | None | None | N |
| N/T | 0.2238 | likely_benign | 0.2158 | benign | -0.684 | Destabilizing | 0.999 | D | 0.701 | prob.neutral | N | 0.514785136 | None | None | N |
| N/V | 0.6634 | likely_pathogenic | 0.6388 | pathogenic | -0.212 | Destabilizing | 1.0 | D | 0.778 | deleterious | None | None | None | None | N |
| N/W | 0.9854 | likely_pathogenic | 0.9855 | pathogenic | -0.325 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | N |
| N/Y | 0.7866 | likely_pathogenic | 0.78 | pathogenic | -0.05 | Destabilizing | 1.0 | D | 0.769 | deleterious | N | 0.469980114 | 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.