Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29649 | 89170;89171;89172 | chr2:178554166;178554165;178554164 | chr2:179418893;179418892;179418891 |
| N2AB | 28008 | 84247;84248;84249 | chr2:178554166;178554165;178554164 | chr2:179418893;179418892;179418891 |
| N2A | 27081 | 81466;81467;81468 | chr2:178554166;178554165;178554164 | chr2:179418893;179418892;179418891 |
| N2B | 20584 | 61975;61976;61977 | chr2:178554166;178554165;178554164 | chr2:179418893;179418892;179418891 |
| Novex-1 | 20709 | 62350;62351;62352 | chr2:178554166;178554165;178554164 | chr2:179418893;179418892;179418891 |
| Novex-2 | 20776 | 62551;62552;62553 | chr2:178554166;178554165;178554164 | chr2:179418893;179418892;179418891 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/L | rs764695663  |
0.356 | 0.859 | D | 0.651 | 0.48 | 0.703810458386 | gnomAD-2.1.1 | 5.76E-05 | None | None | None | None | N | None | 0 | 2.07088E-04 | None | 0 | 0 | None | 6.84E-05 | None | 0 | 2.73E-05 | 3.39328E-04 |
| S/L | rs764695663 |
0.356 | 0.859 | D | 0.651 | 0.48 | 0.703810458386 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 2.41E-05 | 1.30993E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/L | rs764695663 |
0.356 | 0.859 | D | 0.651 | 0.48 | 0.703810458386 | gnomAD-4.0.0 | 1.98743E-05 | None | None | None | None | N | None | 1.34048E-05 | 1.51612E-04 | None | 0 | 2.22955E-05 | None | 0 | 0 | 1.0181E-05 | 3.33267E-05 | 9.62896E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0966 | likely_benign | 0.1233 | benign | -0.421 | Destabilizing | 0.003 | N | 0.193 | neutral | N | 0.486179173 | None | None | N |
| S/C | 0.1013 | likely_benign | 0.1153 | benign | -0.807 | Destabilizing | 0.987 | D | 0.711 | prob.delet. | None | None | None | None | N |
| S/D | 0.7305 | likely_pathogenic | 0.7653 | pathogenic | -1.894 | Destabilizing | 0.742 | D | 0.668 | neutral | None | None | None | None | N |
| S/E | 0.7692 | likely_pathogenic | 0.7904 | pathogenic | -1.847 | Destabilizing | 0.742 | D | 0.653 | neutral | None | None | None | None | N |
| S/F | 0.2359 | likely_benign | 0.3072 | benign | -0.781 | Destabilizing | 0.953 | D | 0.757 | deleterious | None | None | None | None | N |
| S/G | 0.1389 | likely_benign | 0.1606 | benign | -0.658 | Destabilizing | 0.373 | N | 0.555 | neutral | None | None | None | None | N |
| S/H | 0.489 | ambiguous | 0.5238 | ambiguous | -1.208 | Destabilizing | 0.996 | D | 0.711 | prob.delet. | None | None | None | None | N |
| S/I | 0.3785 | ambiguous | 0.463 | ambiguous | 0.108 | Stabilizing | 0.91 | D | 0.739 | prob.delet. | None | None | None | None | N |
| S/K | 0.9283 | likely_pathogenic | 0.9433 | pathogenic | -0.698 | Destabilizing | 0.742 | D | 0.651 | neutral | None | None | None | None | N |
| S/L | 0.1608 | likely_benign | 0.2056 | benign | 0.108 | Stabilizing | 0.859 | D | 0.651 | neutral | D | 0.522845437 | None | None | N |
| S/M | 0.223 | likely_benign | 0.2663 | benign | 0.322 | Stabilizing | 0.984 | D | 0.721 | prob.delet. | None | None | None | None | N |
| S/N | 0.2699 | likely_benign | 0.3086 | benign | -1.164 | Destabilizing | 0.742 | D | 0.632 | neutral | None | None | None | None | N |
| S/P | 0.9847 | likely_pathogenic | 0.9911 | pathogenic | -0.036 | Destabilizing | 0.939 | D | 0.772 | deleterious | D | 0.529593387 | None | None | N |
| S/Q | 0.6937 | likely_pathogenic | 0.7201 | pathogenic | -1.347 | Destabilizing | 0.953 | D | 0.68 | prob.neutral | None | None | None | None | N |
| S/R | 0.8911 | likely_pathogenic | 0.9092 | pathogenic | -0.563 | Destabilizing | 0.953 | D | 0.779 | deleterious | None | None | None | None | N |
| S/T | 0.0949 | likely_benign | 0.1066 | benign | -0.861 | Destabilizing | 0.004 | N | 0.152 | neutral | N | 0.479736773 | None | None | N |
| S/V | 0.3206 | likely_benign | 0.3977 | ambiguous | -0.036 | Destabilizing | 0.59 | D | 0.655 | neutral | None | None | None | None | N |
| S/W | 0.5108 | ambiguous | 0.5637 | ambiguous | -0.965 | Destabilizing | 0.998 | D | 0.731 | prob.delet. | N | 0.506716192 | None | None | N |
| S/Y | 0.255 | likely_benign | 0.3065 | benign | -0.538 | Destabilizing | 0.984 | D | 0.731 | prob.delet. | 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.