Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17475 | 52648;52649;52650 | chr2:178608460;178608459;178608458 | chr2:179473187;179473186;179473185 |
| N2AB | 15834 | 47725;47726;47727 | chr2:178608460;178608459;178608458 | chr2:179473187;179473186;179473185 |
| N2A | 14907 | 44944;44945;44946 | chr2:178608460;178608459;178608458 | chr2:179473187;179473186;179473185 |
| N2B | 8410 | 25453;25454;25455 | chr2:178608460;178608459;178608458 | chr2:179473187;179473186;179473185 |
| Novex-1 | 8535 | 25828;25829;25830 | chr2:178608460;178608459;178608458 | chr2:179473187;179473186;179473185 |
| Novex-2 | 8602 | 26029;26030;26031 | chr2:178608460;178608459;178608458 | chr2:179473187;179473186;179473185 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | rs1176767614  |
-0.538 | 0.003 | N | 0.097 | 0.03 | 0.223146558224 | gnomAD-2.1.1 | 4.35E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.77936E-04 |
| D/E | rs1176767614 |
-0.538 | 0.003 | N | 0.097 | 0.03 | 0.223146558224 | gnomAD-4.0.0 | 1.62648E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.07409E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1567 | likely_benign | 0.1537 | benign | -0.315 | Destabilizing | 0.722 | D | 0.686 | prob.neutral | N | 0.423837844 | None | None | N |
| D/C | 0.5465 | ambiguous | 0.543 | ambiguous | -0.179 | Destabilizing | 0.996 | D | 0.801 | deleterious | None | None | None | None | N |
| D/E | 0.1301 | likely_benign | 0.1274 | benign | -0.654 | Destabilizing | 0.003 | N | 0.097 | neutral | N | 0.394360299 | None | None | N |
| D/F | 0.6835 | likely_pathogenic | 0.664 | pathogenic | -0.038 | Destabilizing | 0.987 | D | 0.771 | deleterious | None | None | None | None | N |
| D/G | 0.1246 | likely_benign | 0.1221 | benign | -0.625 | Destabilizing | 0.565 | D | 0.58 | neutral | N | 0.390917349 | None | None | N |
| D/H | 0.3471 | ambiguous | 0.3391 | benign | -0.353 | Destabilizing | 0.901 | D | 0.696 | prob.neutral | N | 0.505069574 | None | None | N |
| D/I | 0.4535 | ambiguous | 0.4499 | ambiguous | 0.487 | Stabilizing | 0.961 | D | 0.78 | deleterious | None | None | None | None | N |
| D/K | 0.3635 | ambiguous | 0.3776 | ambiguous | -0.362 | Destabilizing | 0.633 | D | 0.603 | neutral | None | None | None | None | N |
| D/L | 0.3708 | ambiguous | 0.3538 | ambiguous | 0.487 | Stabilizing | 0.923 | D | 0.731 | prob.delet. | None | None | None | None | N |
| D/M | 0.6082 | likely_pathogenic | 0.6034 | pathogenic | 0.735 | Stabilizing | 0.996 | D | 0.755 | deleterious | None | None | None | None | N |
| D/N | 0.109 | likely_benign | 0.1027 | benign | -0.664 | Destabilizing | 0.003 | N | 0.125 | neutral | N | 0.43594035 | None | None | N |
| D/P | 0.5763 | likely_pathogenic | 0.6333 | pathogenic | 0.245 | Stabilizing | 0.961 | D | 0.704 | prob.neutral | None | None | None | None | N |
| D/Q | 0.2947 | likely_benign | 0.2913 | benign | -0.539 | Destabilizing | 0.858 | D | 0.55 | neutral | None | None | None | None | N |
| D/R | 0.4468 | ambiguous | 0.4528 | ambiguous | -0.196 | Destabilizing | 0.923 | D | 0.717 | prob.delet. | None | None | None | None | N |
| D/S | 0.1163 | likely_benign | 0.1131 | benign | -0.841 | Destabilizing | 0.633 | D | 0.484 | neutral | None | None | None | None | N |
| D/T | 0.2524 | likely_benign | 0.2458 | benign | -0.601 | Destabilizing | 0.775 | D | 0.645 | neutral | None | None | None | None | N |
| D/V | 0.2696 | likely_benign | 0.2612 | benign | 0.245 | Stabilizing | 0.949 | D | 0.735 | prob.delet. | N | 0.458470493 | None | None | N |
| D/W | 0.8967 | likely_pathogenic | 0.9023 | pathogenic | 0.067 | Stabilizing | 0.996 | D | 0.769 | deleterious | None | None | None | None | N |
| D/Y | 0.3162 | likely_benign | 0.3043 | benign | 0.163 | Stabilizing | 0.983 | D | 0.776 | deleterious | N | 0.473093229 | 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.