Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2878 | 8857;8858;8859 | chr2:178770069;178770068;178770067 | chr2:179634796;179634795;179634794 |
| N2AB | 2878 | 8857;8858;8859 | chr2:178770069;178770068;178770067 | chr2:179634796;179634795;179634794 |
| N2A | 2878 | 8857;8858;8859 | chr2:178770069;178770068;178770067 | chr2:179634796;179634795;179634794 |
| N2B | 2832 | 8719;8720;8721 | chr2:178770069;178770068;178770067 | chr2:179634796;179634795;179634794 |
| Novex-1 | 2832 | 8719;8720;8721 | chr2:178770069;178770068;178770067 | chr2:179634796;179634795;179634794 |
| Novex-2 | 2832 | 8719;8720;8721 | chr2:178770069;178770068;178770067 | chr2:179634796;179634795;179634794 |
| Novex-3 | 2878 | 8857;8858;8859 | chr2:178770069;178770068;178770067 | chr2:179634796;179634795;179634794 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/I | rs2091250841  |
None | 0.92 | N | 0.305 | 0.226 | 0.326345978581 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| F/I | rs2091250841 |
None | 0.92 | N | 0.305 | 0.226 | 0.326345978581 | gnomAD-4.0.0 | 2.56115E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.39172E-06 | 0 | 2.84188E-05 |
| F/L | None | None | 0.826 | N | 0.327 | 0.211 | 0.200317383148 | gnomAD-4.0.0 | 1.59047E-06 | None | None | None | None | N | None | 0 | 2.28645E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| F/S | rs2091250535 |
None | 0.704 | N | 0.319 | 0.238 | 0.655252992372 | gnomAD-4.0.0 | 1.36813E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99292E-07 | 0 | 1.65579E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.6661 | likely_pathogenic | 0.6316 | pathogenic | -1.832 | Destabilizing | 0.079 | N | 0.181 | neutral | None | None | None | None | N |
| F/C | 0.5771 | likely_pathogenic | 0.542 | ambiguous | -0.56 | Destabilizing | 0.999 | D | 0.331 | neutral | N | 0.449761029 | None | None | N |
| F/D | 0.8487 | likely_pathogenic | 0.8298 | pathogenic | -0.217 | Destabilizing | 0.969 | D | 0.362 | neutral | None | None | None | None | N |
| F/E | 0.8625 | likely_pathogenic | 0.8382 | pathogenic | -0.195 | Destabilizing | 0.969 | D | 0.355 | neutral | None | None | None | None | N |
| F/G | 0.8998 | likely_pathogenic | 0.8937 | pathogenic | -2.113 | Highly Destabilizing | 0.884 | D | 0.362 | neutral | None | None | None | None | N |
| F/H | 0.5031 | ambiguous | 0.4879 | ambiguous | -0.493 | Destabilizing | 0.997 | D | 0.345 | neutral | None | None | None | None | N |
| F/I | 0.3259 | likely_benign | 0.29 | benign | -1.029 | Destabilizing | 0.92 | D | 0.305 | neutral | N | 0.424951337 | None | None | N |
| F/K | 0.8712 | likely_pathogenic | 0.8482 | pathogenic | -0.662 | Destabilizing | 0.939 | D | 0.351 | neutral | None | None | None | None | N |
| F/L | 0.8875 | likely_pathogenic | 0.8602 | pathogenic | -1.029 | Destabilizing | 0.826 | D | 0.327 | neutral | N | 0.436650378 | None | None | N |
| F/M | 0.6159 | likely_pathogenic | 0.5976 | pathogenic | -0.649 | Destabilizing | 0.997 | D | 0.359 | neutral | None | None | None | None | N |
| F/N | 0.6115 | likely_pathogenic | 0.5904 | pathogenic | -0.506 | Destabilizing | 0.991 | D | 0.357 | neutral | None | None | None | None | N |
| F/P | 0.9976 | likely_pathogenic | 0.9968 | pathogenic | -1.284 | Destabilizing | 0.991 | D | 0.357 | neutral | None | None | None | None | N |
| F/Q | 0.7551 | likely_pathogenic | 0.7325 | pathogenic | -0.653 | Destabilizing | 0.997 | D | 0.369 | neutral | None | None | None | None | N |
| F/R | 0.7534 | likely_pathogenic | 0.7295 | pathogenic | 0.007 | Stabilizing | 0.991 | D | 0.358 | neutral | None | None | None | None | N |
| F/S | 0.4455 | ambiguous | 0.4096 | ambiguous | -1.279 | Destabilizing | 0.704 | D | 0.319 | neutral | N | 0.433598168 | None | None | N |
| F/T | 0.4672 | ambiguous | 0.4354 | ambiguous | -1.168 | Destabilizing | 0.079 | N | 0.171 | neutral | None | None | None | None | N |
| F/V | 0.341 | ambiguous | 0.2994 | benign | -1.284 | Destabilizing | 0.826 | D | 0.347 | neutral | N | 0.433026657 | None | None | N |
| F/W | 0.64 | likely_pathogenic | 0.6573 | pathogenic | -0.514 | Destabilizing | 0.999 | D | 0.383 | neutral | None | None | None | None | N |
| F/Y | 0.2078 | likely_benign | 0.2097 | benign | -0.616 | Destabilizing | 0.986 | D | 0.358 | neutral | N | 0.447627635 | 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.