Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1597 | 5014;5015;5016 | chr2:178777174;178777173;178777172 | chr2:179641901;179641900;179641899 |
| N2AB | 1597 | 5014;5015;5016 | chr2:178777174;178777173;178777172 | chr2:179641901;179641900;179641899 |
| N2A | 1597 | 5014;5015;5016 | chr2:178777174;178777173;178777172 | chr2:179641901;179641900;179641899 |
| N2B | 1551 | 4876;4877;4878 | chr2:178777174;178777173;178777172 | chr2:179641901;179641900;179641899 |
| Novex-1 | 1551 | 4876;4877;4878 | chr2:178777174;178777173;178777172 | chr2:179641901;179641900;179641899 |
| Novex-2 | 1551 | 4876;4877;4878 | chr2:178777174;178777173;178777172 | chr2:179641901;179641900;179641899 |
| Novex-3 | 1597 | 5014;5015;5016 | chr2:178777174;178777173;178777172 | chr2:179641901;179641900;179641899 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/L | rs878928245  |
None | 0.08 | N | 0.235 | 0.12 | 0.486494567076 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/L | rs878928245 |
None | 0.08 | N | 0.235 | 0.12 | 0.486494567076 | gnomAD-4.0.0 | 2.47836E-06 | None | None | None | None | N | None | 4.00502E-05 | 1.66678E-05 | None | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.6065 | likely_pathogenic | 0.5023 | ambiguous | -1.336 | Destabilizing | 0.002 | N | 0.09 | neutral | N | 0.465332399 | None | None | N |
| V/C | 0.9477 | likely_pathogenic | 0.9251 | pathogenic | -0.62 | Destabilizing | 0.972 | D | 0.363 | neutral | None | None | None | None | N |
| V/D | 0.9386 | likely_pathogenic | 0.8807 | pathogenic | -1.453 | Destabilizing | 0.617 | D | 0.411 | neutral | None | None | None | None | N |
| V/E | 0.8676 | likely_pathogenic | 0.7808 | pathogenic | -1.413 | Destabilizing | 0.549 | D | 0.374 | neutral | N | 0.474546822 | None | None | N |
| V/F | 0.4829 | ambiguous | 0.3817 | ambiguous | -1.0 | Destabilizing | 0.85 | D | 0.391 | neutral | None | None | None | None | N |
| V/G | 0.7799 | likely_pathogenic | 0.6895 | pathogenic | -1.658 | Destabilizing | 0.201 | N | 0.392 | neutral | N | 0.493716847 | None | None | N |
| V/H | 0.9341 | likely_pathogenic | 0.894 | pathogenic | -1.223 | Destabilizing | 0.992 | D | 0.408 | neutral | None | None | None | None | N |
| V/I | 0.1211 | likely_benign | 0.1045 | benign | -0.536 | Destabilizing | 0.25 | N | 0.318 | neutral | None | None | None | None | N |
| V/K | 0.9122 | likely_pathogenic | 0.8543 | pathogenic | -1.15 | Destabilizing | 0.617 | D | 0.371 | neutral | None | None | None | None | N |
| V/L | 0.4645 | ambiguous | 0.3726 | ambiguous | -0.536 | Destabilizing | 0.08 | N | 0.235 | neutral | N | 0.491848464 | None | None | N |
| V/M | 0.4233 | ambiguous | 0.3339 | benign | -0.359 | Destabilizing | 0.036 | N | 0.159 | neutral | N | 0.501585557 | None | None | N |
| V/N | 0.8475 | likely_pathogenic | 0.7593 | pathogenic | -1.006 | Destabilizing | 0.617 | D | 0.433 | neutral | None | None | None | None | N |
| V/P | 0.9626 | likely_pathogenic | 0.9372 | pathogenic | -0.771 | Destabilizing | 0.92 | D | 0.403 | neutral | None | None | None | None | N |
| V/Q | 0.836 | likely_pathogenic | 0.7614 | pathogenic | -1.119 | Destabilizing | 0.92 | D | 0.405 | neutral | None | None | None | None | N |
| V/R | 0.8688 | likely_pathogenic | 0.81 | pathogenic | -0.676 | Destabilizing | 0.85 | D | 0.426 | neutral | None | None | None | None | N |
| V/S | 0.6078 | likely_pathogenic | 0.5113 | ambiguous | -1.434 | Destabilizing | 0.026 | N | 0.197 | neutral | None | None | None | None | N |
| V/T | 0.5704 | likely_pathogenic | 0.4629 | ambiguous | -1.289 | Destabilizing | 0.021 | N | 0.116 | neutral | None | None | None | None | N |
| V/W | 0.9826 | likely_pathogenic | 0.9709 | pathogenic | -1.29 | Destabilizing | 0.992 | D | 0.449 | neutral | None | None | None | None | N |
| V/Y | 0.9078 | likely_pathogenic | 0.858 | pathogenic | -0.95 | Destabilizing | 0.92 | D | 0.383 | 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.