Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16177 | 48754;48755;48756 | chr2:178615416;178615415;178615414 | chr2:179480143;179480142;179480141 |
| N2AB | 14536 | 43831;43832;43833 | chr2:178615416;178615415;178615414 | chr2:179480143;179480142;179480141 |
| N2A | 13609 | 41050;41051;41052 | chr2:178615416;178615415;178615414 | chr2:179480143;179480142;179480141 |
| N2B | 7112 | 21559;21560;21561 | chr2:178615416;178615415;178615414 | chr2:179480143;179480142;179480141 |
| Novex-1 | 7237 | 21934;21935;21936 | chr2:178615416;178615415;178615414 | chr2:179480143;179480142;179480141 |
| Novex-2 | 7304 | 22135;22136;22137 | chr2:178615416;178615415;178615414 | chr2:179480143;179480142;179480141 |
| 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/H | rs1383656849  |
-0.556 | 0.484 | N | 0.585 | 0.373 | 0.241664281697 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.1162E-04 | None | 0 | None | 0 | 0 | 0 |
| D/H | rs1383656849 |
-0.556 | 0.484 | N | 0.585 | 0.373 | 0.241664281697 | gnomAD-4.0.0 | 3.18734E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.5534E-05 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.2559 | likely_benign | 0.2243 | benign | -0.415 | Destabilizing | 0.062 | N | 0.501 | neutral | N | 0.448660469 | None | None | N |
| D/C | 0.7728 | likely_pathogenic | 0.7351 | pathogenic | -0.216 | Destabilizing | 0.935 | D | 0.645 | neutral | None | None | None | None | N |
| D/E | 0.1096 | likely_benign | 0.1107 | benign | -0.845 | Destabilizing | None | N | 0.145 | neutral | N | 0.352549859 | None | None | N |
| D/F | 0.6934 | likely_pathogenic | 0.6805 | pathogenic | -0.265 | Destabilizing | 0.791 | D | 0.619 | neutral | None | None | None | None | N |
| D/G | 0.4518 | ambiguous | 0.3742 | ambiguous | -0.751 | Destabilizing | 0.117 | N | 0.455 | neutral | N | 0.480317393 | None | None | N |
| D/H | 0.4768 | ambiguous | 0.4385 | ambiguous | -0.702 | Destabilizing | 0.484 | N | 0.585 | neutral | N | 0.482789729 | None | None | N |
| D/I | 0.3869 | ambiguous | 0.3836 | ambiguous | 0.462 | Stabilizing | 0.555 | D | 0.629 | neutral | None | None | None | None | N |
| D/K | 0.533 | ambiguous | 0.4975 | ambiguous | -0.579 | Destabilizing | 0.081 | N | 0.455 | neutral | None | None | None | None | N |
| D/L | 0.3704 | ambiguous | 0.3556 | ambiguous | 0.462 | Stabilizing | 0.38 | N | 0.605 | neutral | None | None | None | None | N |
| D/M | 0.5555 | ambiguous | 0.5537 | ambiguous | 0.892 | Stabilizing | 0.935 | D | 0.614 | neutral | None | None | None | None | N |
| D/N | 0.1449 | likely_benign | 0.1472 | benign | -0.875 | Destabilizing | 0.117 | N | 0.42 | neutral | N | 0.460032589 | None | None | N |
| D/P | 0.9741 | likely_pathogenic | 0.9569 | pathogenic | 0.196 | Stabilizing | 0.555 | D | 0.587 | neutral | None | None | None | None | N |
| D/Q | 0.377 | ambiguous | 0.3547 | ambiguous | -0.735 | Destabilizing | 0.081 | N | 0.396 | neutral | None | None | None | None | N |
| D/R | 0.6551 | likely_pathogenic | 0.6071 | pathogenic | -0.473 | Destabilizing | 0.235 | N | 0.626 | neutral | None | None | None | None | N |
| D/S | 0.2 | likely_benign | 0.19 | benign | -1.109 | Destabilizing | 0.081 | N | 0.413 | neutral | None | None | None | None | N |
| D/T | 0.2813 | likely_benign | 0.2817 | benign | -0.847 | Destabilizing | 0.149 | N | 0.509 | neutral | None | None | None | None | N |
| D/V | 0.2511 | likely_benign | 0.2388 | benign | 0.196 | Stabilizing | 0.317 | N | 0.593 | neutral | N | 0.461616234 | None | None | N |
| D/W | 0.9323 | likely_pathogenic | 0.9249 | pathogenic | -0.221 | Destabilizing | 0.935 | D | 0.649 | neutral | None | None | None | None | N |
| D/Y | 0.3833 | ambiguous | 0.3533 | ambiguous | -0.081 | Destabilizing | 0.741 | D | 0.619 | neutral | N | 0.473184971 | 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.