Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21981 | 66166;66167;66168 | chr2:178582515;178582514;178582513 | chr2:179447242;179447241;179447240 |
| N2AB | 20340 | 61243;61244;61245 | chr2:178582515;178582514;178582513 | chr2:179447242;179447241;179447240 |
| N2A | 19413 | 58462;58463;58464 | chr2:178582515;178582514;178582513 | chr2:179447242;179447241;179447240 |
| N2B | 12916 | 38971;38972;38973 | chr2:178582515;178582514;178582513 | chr2:179447242;179447241;179447240 |
| Novex-1 | 13041 | 39346;39347;39348 | chr2:178582515;178582514;178582513 | chr2:179447242;179447241;179447240 |
| Novex-2 | 13108 | 39547;39548;39549 | chr2:178582515;178582514;178582513 | chr2:179447242;179447241;179447240 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/F | rs1414709360  |
-0.542 | 0.998 | N | 0.706 | 0.362 | 0.366277470483 | gnomAD-2.1.1 | 7.16E-06 | None | None | None | None | N | None | 4.14E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 7.84E-06 | 0 |
| L/F | rs1414709360 |
-0.542 | 0.998 | N | 0.706 | 0.362 | 0.366277470483 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| L/F | rs1414709360 |
-0.542 | 0.998 | N | 0.706 | 0.362 | 0.366277470483 | gnomAD-4.0.0 | 3.72004E-06 | None | None | None | None | N | None | 1.3359E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 4.23967E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.1569 | likely_benign | 0.1323 | benign | -0.403 | Destabilizing | 0.968 | D | 0.57 | neutral | None | None | None | None | N |
| L/C | 0.6068 | likely_pathogenic | 0.5047 | ambiguous | -0.629 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | None | None | None | None | N |
| L/D | 0.6519 | likely_pathogenic | 0.5374 | ambiguous | -0.186 | Destabilizing | 0.982 | D | 0.712 | prob.delet. | None | None | None | None | N |
| L/E | 0.2541 | likely_benign | 0.1989 | benign | -0.291 | Destabilizing | 0.18 | N | 0.446 | neutral | None | None | None | None | N |
| L/F | 0.2222 | likely_benign | 0.1903 | benign | -0.557 | Destabilizing | 0.998 | D | 0.706 | prob.neutral | N | 0.505829321 | None | None | N |
| L/G | 0.4935 | ambiguous | 0.4025 | ambiguous | -0.522 | Destabilizing | 0.991 | D | 0.72 | prob.delet. | None | None | None | None | N |
| L/H | 0.3103 | likely_benign | 0.2453 | benign | 0.092 | Stabilizing | 0.998 | D | 0.712 | prob.delet. | N | 0.477293813 | None | None | N |
| L/I | 0.101 | likely_benign | 0.0942 | benign | -0.222 | Destabilizing | 0.979 | D | 0.553 | neutral | N | 0.511496901 | None | None | N |
| L/K | 0.1844 | likely_benign | 0.1388 | benign | -0.245 | Destabilizing | 0.982 | D | 0.593 | neutral | None | None | None | None | N |
| L/M | 0.1145 | likely_benign | 0.1061 | benign | -0.405 | Destabilizing | 0.998 | D | 0.688 | prob.neutral | None | None | None | None | N |
| L/N | 0.4007 | ambiguous | 0.3129 | benign | -0.055 | Destabilizing | 0.991 | D | 0.727 | prob.delet. | None | None | None | None | N |
| L/P | 0.3726 | ambiguous | 0.2612 | benign | -0.252 | Destabilizing | 0.994 | D | 0.733 | prob.delet. | N | 0.466707522 | None | None | N |
| L/Q | 0.1312 | likely_benign | 0.1089 | benign | -0.277 | Destabilizing | 0.982 | D | 0.681 | prob.neutral | None | None | None | None | N |
| L/R | 0.1924 | likely_benign | 0.1452 | benign | 0.261 | Stabilizing | 0.988 | D | 0.681 | prob.neutral | N | 0.519460237 | None | None | N |
| L/S | 0.2433 | likely_benign | 0.1871 | benign | -0.444 | Destabilizing | 0.991 | D | 0.606 | neutral | None | None | None | None | N |
| L/T | 0.17 | likely_benign | 0.1423 | benign | -0.445 | Destabilizing | 0.991 | D | 0.621 | neutral | None | None | None | None | N |
| L/V | 0.0876 | likely_benign | 0.0828 | benign | -0.252 | Destabilizing | 0.979 | D | 0.558 | neutral | N | 0.489697477 | None | None | N |
| L/W | 0.4161 | ambiguous | 0.3232 | benign | -0.581 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | N |
| L/Y | 0.4792 | ambiguous | 0.3882 | ambiguous | -0.323 | Destabilizing | 0.998 | D | 0.699 | prob.neutral | 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.