Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14522 | 43789;43790;43791 | chr2:178632330;178632329;178632328 | chr2:179497057;179497056;179497055 |
| N2AB | 12881 | 38866;38867;38868 | chr2:178632330;178632329;178632328 | chr2:179497057;179497056;179497055 |
| N2A | 11954 | 36085;36086;36087 | chr2:178632330;178632329;178632328 | chr2:179497057;179497056;179497055 |
| N2B | 5457 | 16594;16595;16596 | chr2:178632330;178632329;178632328 | chr2:179497057;179497056;179497055 |
| Novex-1 | 5582 | 16969;16970;16971 | chr2:178632330;178632329;178632328 | chr2:179497057;179497056;179497055 |
| Novex-2 | 5649 | 17170;17171;17172 | chr2:178632330;178632329;178632328 | chr2:179497057;179497056;179497055 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| H/D | None | None | 1.0 | D | 0.682 | 0.499 | 0.47432691512 | gnomAD-4.0.0 | 6.87452E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.02226E-07 | 0 | 0 |
| H/P | None | None | 1.0 | N | 0.7 | 0.586 | 0.502878934189 | gnomAD-4.0.0 | 4.81666E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.32315E-06 | 0 | 0 |
| H/R | rs374085402  |
-0.665 | 1.0 | D | 0.705 | 0.356 | None | gnomAD-2.1.1 | 5.5E-05 | None | None | None | None | N | None | 0 | 9.05E-05 | None | 0 | 4.73765E-04 | None | 3.44E-05 | None | 0 | 0 | 1.72058E-04 |
| H/R | rs374085402 |
-0.665 | 1.0 | D | 0.705 | 0.356 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.94024E-04 | None | 0 | 0 | 0 | 0 | 0 |
| H/R | rs374085402 |
-0.665 | 1.0 | D | 0.705 | 0.356 | None | gnomAD-4.0.0 | 1.99282E-05 | None | None | None | None | N | None | 0 | 5.07597E-05 | None | 0 | 2.70161E-04 | None | 0 | 0 | 8.50737E-07 | 0 | 2.57375E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| H/A | 0.9058 | likely_pathogenic | 0.8524 | pathogenic | 0.02 | Stabilizing | 0.999 | D | 0.611 | neutral | None | None | None | None | N |
| H/C | 0.6898 | likely_pathogenic | 0.6028 | pathogenic | 0.565 | Stabilizing | 1.0 | D | 0.75 | deleterious | None | None | None | None | N |
| H/D | 0.843 | likely_pathogenic | 0.7997 | pathogenic | -0.319 | Destabilizing | 1.0 | D | 0.682 | prob.neutral | D | 0.562348889 | None | None | N |
| H/E | 0.8993 | likely_pathogenic | 0.8269 | pathogenic | -0.245 | Destabilizing | 0.999 | D | 0.572 | neutral | None | None | None | None | N |
| H/F | 0.8416 | likely_pathogenic | 0.7536 | pathogenic | 1.111 | Stabilizing | 1.0 | D | 0.678 | prob.neutral | None | None | None | None | N |
| H/G | 0.9167 | likely_pathogenic | 0.8739 | pathogenic | -0.325 | Destabilizing | 0.999 | D | 0.619 | neutral | None | None | None | None | N |
| H/I | 0.9466 | likely_pathogenic | 0.9035 | pathogenic | 0.942 | Stabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | N |
| H/K | 0.8497 | likely_pathogenic | 0.7525 | pathogenic | 0.055 | Stabilizing | 1.0 | D | 0.677 | prob.neutral | None | None | None | None | N |
| H/L | 0.6521 | likely_pathogenic | 0.5441 | ambiguous | 0.942 | Stabilizing | 1.0 | D | 0.743 | deleterious | D | 0.646718956 | None | None | N |
| H/M | 0.9482 | likely_pathogenic | 0.918 | pathogenic | 0.607 | Stabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | N |
| H/N | 0.5998 | likely_pathogenic | 0.5099 | ambiguous | -0.112 | Destabilizing | 0.999 | D | 0.576 | neutral | D | 0.582296109 | None | None | N |
| H/P | 0.8205 | likely_pathogenic | 0.8244 | pathogenic | 0.658 | Stabilizing | 1.0 | D | 0.7 | prob.neutral | N | 0.502141643 | None | None | N |
| H/Q | 0.839 | likely_pathogenic | 0.7103 | pathogenic | 0.088 | Stabilizing | 1.0 | D | 0.7 | prob.neutral | D | 0.606543758 | None | None | N |
| H/R | 0.5565 | ambiguous | 0.3899 | ambiguous | -0.649 | Destabilizing | 1.0 | D | 0.705 | prob.neutral | D | 0.582442759 | None | None | N |
| H/S | 0.8226 | likely_pathogenic | 0.7653 | pathogenic | 0.018 | Stabilizing | 1.0 | D | 0.648 | neutral | None | None | None | None | N |
| H/T | 0.9285 | likely_pathogenic | 0.8841 | pathogenic | 0.204 | Stabilizing | 1.0 | D | 0.714 | prob.delet. | None | None | None | None | N |
| H/V | 0.9077 | likely_pathogenic | 0.8427 | pathogenic | 0.658 | Stabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | N |
| H/W | 0.7772 | likely_pathogenic | 0.6992 | pathogenic | 1.249 | Stabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | N |
| H/Y | 0.4406 | ambiguous | 0.3192 | benign | 1.384 | Stabilizing | 0.999 | D | 0.586 | neutral | D | 0.646833121 | 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.