Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2150 | 6673;6674;6675 | chr2:178775416;178775415;178775414 | chr2:179640143;179640142;179640141 |
| N2AB | 2150 | 6673;6674;6675 | chr2:178775416;178775415;178775414 | chr2:179640143;179640142;179640141 |
| N2A | 2150 | 6673;6674;6675 | chr2:178775416;178775415;178775414 | chr2:179640143;179640142;179640141 |
| N2B | 2104 | 6535;6536;6537 | chr2:178775416;178775415;178775414 | chr2:179640143;179640142;179640141 |
| Novex-1 | 2104 | 6535;6536;6537 | chr2:178775416;178775415;178775414 | chr2:179640143;179640142;179640141 |
| Novex-2 | 2104 | 6535;6536;6537 | chr2:178775416;178775415;178775414 | chr2:179640143;179640142;179640141 |
| Novex-3 | 2150 | 6673;6674;6675 | chr2:178775416;178775415;178775414 | chr2:179640143;179640142;179640141 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/T | rs761352132  |
-1.198 | 0.994 | N | 0.485 | 0.573 | 0.726484281749 | gnomAD-2.1.1 | 1.59E-05 | None | None | None | None | N | None | 6.15E-05 | 0 | None | 9.94E-05 | 0 | None | 0 | None | 0 | 1.76E-05 | 0 |
| M/T | rs761352132 |
-1.198 | 0.994 | N | 0.485 | 0.573 | 0.726484281749 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| M/T | rs761352132 |
-1.198 | 0.994 | N | 0.485 | 0.573 | 0.726484281749 | gnomAD-4.0.0 | 1.92074E-05 | None | None | None | None | N | None | 4.00459E-05 | 0 | None | 3.37792E-05 | 0 | None | 0 | 0 | 2.20335E-05 | 0 | 1.60056E-05 |
| M/V | None | None | 0.985 | N | 0.549 | 0.38 | 0.686849864873 | gnomAD-4.0.0 | 4.77202E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.56957E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.7581 | likely_pathogenic | 0.8065 | pathogenic | -1.959 | Destabilizing | 0.989 | D | 0.555 | neutral | None | None | None | None | N |
| M/C | 0.9501 | likely_pathogenic | 0.9508 | pathogenic | -1.718 | Destabilizing | 1.0 | D | 0.637 | neutral | None | None | None | None | N |
| M/D | 0.9887 | likely_pathogenic | 0.9917 | pathogenic | -1.426 | Destabilizing | 0.999 | D | 0.722 | prob.delet. | None | None | None | None | N |
| M/E | 0.915 | likely_pathogenic | 0.9366 | pathogenic | -1.209 | Destabilizing | 0.999 | D | 0.606 | neutral | None | None | None | None | N |
| M/F | 0.7511 | likely_pathogenic | 0.7444 | pathogenic | -0.543 | Destabilizing | 0.999 | D | 0.455 | neutral | None | None | None | None | N |
| M/G | 0.9375 | likely_pathogenic | 0.9517 | pathogenic | -2.437 | Highly Destabilizing | 0.995 | D | 0.645 | neutral | None | None | None | None | N |
| M/H | 0.8992 | likely_pathogenic | 0.9118 | pathogenic | -2.058 | Highly Destabilizing | 1.0 | D | 0.722 | prob.delet. | None | None | None | None | N |
| M/I | 0.8566 | likely_pathogenic | 0.8843 | pathogenic | -0.605 | Destabilizing | 0.985 | D | 0.565 | neutral | N | 0.485558266 | None | None | N |
| M/K | 0.7608 | likely_pathogenic | 0.8056 | pathogenic | -0.943 | Destabilizing | 0.994 | D | 0.492 | neutral | N | 0.423027106 | None | None | N |
| M/L | 0.3915 | ambiguous | 0.4248 | ambiguous | -0.605 | Destabilizing | 0.927 | D | 0.509 | neutral | N | 0.500231471 | None | None | N |
| M/N | 0.8986 | likely_pathogenic | 0.9192 | pathogenic | -1.239 | Destabilizing | 0.999 | D | 0.677 | prob.neutral | None | None | None | None | N |
| M/P | 0.9986 | likely_pathogenic | 0.9988 | pathogenic | -1.036 | Destabilizing | 0.999 | D | 0.672 | neutral | None | None | None | None | N |
| M/Q | 0.6666 | likely_pathogenic | 0.7132 | pathogenic | -0.944 | Destabilizing | 0.999 | D | 0.456 | neutral | None | None | None | None | N |
| M/R | 0.7887 | likely_pathogenic | 0.8274 | pathogenic | -1.091 | Destabilizing | 0.998 | D | 0.553 | neutral | N | 0.470473088 | None | None | N |
| M/S | 0.7385 | likely_pathogenic | 0.7842 | pathogenic | -1.866 | Destabilizing | 0.995 | D | 0.478 | neutral | None | None | None | None | N |
| M/T | 0.4855 | ambiguous | 0.5634 | ambiguous | -1.515 | Destabilizing | 0.994 | D | 0.485 | neutral | N | 0.375420249 | None | None | N |
| M/V | 0.3425 | ambiguous | 0.3952 | ambiguous | -1.036 | Destabilizing | 0.985 | D | 0.549 | neutral | N | 0.448404643 | None | None | N |
| M/W | 0.9587 | likely_pathogenic | 0.9633 | pathogenic | -0.838 | Destabilizing | 1.0 | D | 0.649 | neutral | None | None | None | None | N |
| M/Y | 0.9301 | likely_pathogenic | 0.9364 | pathogenic | -0.783 | Destabilizing | 0.999 | D | 0.605 | 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.