Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1330 | 4213;4214;4215 | chr2:178779094;178779093;178779092 | chr2:179643821;179643820;179643819 |
| N2AB | 1330 | 4213;4214;4215 | chr2:178779094;178779093;178779092 | chr2:179643821;179643820;179643819 |
| N2A | 1330 | 4213;4214;4215 | chr2:178779094;178779093;178779092 | chr2:179643821;179643820;179643819 |
| N2B | 1284 | 4075;4076;4077 | chr2:178779094;178779093;178779092 | chr2:179643821;179643820;179643819 |
| Novex-1 | 1284 | 4075;4076;4077 | chr2:178779094;178779093;178779092 | chr2:179643821;179643820;179643819 |
| Novex-2 | 1284 | 4075;4076;4077 | chr2:178779094;178779093;178779092 | chr2:179643821;179643820;179643819 |
| Novex-3 | 1330 | 4213;4214;4215 | chr2:178779094;178779093;178779092 | chr2:179643821;179643820;179643819 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/C | rs771294359  |
-0.235 | 1.0 | N | 0.753 | 0.536 | 0.729979875932 | gnomAD-2.1.1 | 1.32039E-04 | None | None | None | None | N | None | 0 | 5.79744E-04 | None | 0 | 0 | None | 2.28878E-04 | None | 0 | 2.66E-05 | 4.93097E-04 |
| R/C | rs771294359 |
-0.235 | 1.0 | N | 0.753 | 0.536 | 0.729979875932 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/C | rs771294359 |
-0.235 | 1.0 | N | 0.753 | 0.536 | 0.729979875932 | gnomAD-4.0.0 | 4.21362E-05 | None | None | None | None | N | None | 2.6656E-05 | 4.00187E-04 | None | 0 | 4.46209E-05 | None | 0 | 0 | 2.11874E-05 | 1.31761E-04 | 4.80046E-05 |
| R/H | rs761402128 |
-0.757 | 1.0 | N | 0.769 | 0.385 | None | gnomAD-2.1.1 | 4.4E-05 | None | None | None | None | N | None | 6.16E-05 | 8.7E-05 | None | 0 | 0 | None | 0 | None | 0 | 5.33E-05 | 1.6442E-04 |
| R/H | rs761402128 |
-0.757 | 1.0 | N | 0.769 | 0.385 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 7.24E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/H | rs761402128 |
-0.757 | 1.0 | N | 0.769 | 0.385 | None | gnomAD-4.0.0 | 4.09007E-05 | None | None | None | None | N | None | 5.33988E-05 | 6.67156E-05 | None | 0 | 8.92339E-05 | None | 0 | 0 | 4.06802E-05 | 4.3929E-05 | 3.20164E-05 |
| R/L | None | None | 1.0 | N | 0.635 | 0.504 | 0.630199317251 | gnomAD-4.0.0 | 6.84231E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15972E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9345 | likely_pathogenic | 0.9442 | pathogenic | -0.393 | Destabilizing | 0.999 | D | 0.653 | neutral | None | None | None | None | N |
| R/C | 0.7973 | likely_pathogenic | 0.7898 | pathogenic | -0.472 | Destabilizing | 1.0 | D | 0.753 | deleterious | N | 0.506150684 | None | None | N |
| R/D | 0.988 | likely_pathogenic | 0.9899 | pathogenic | -0.038 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | N |
| R/E | 0.8775 | likely_pathogenic | 0.8928 | pathogenic | 0.11 | Stabilizing | 0.999 | D | 0.706 | prob.neutral | None | None | None | None | N |
| R/F | 0.9733 | likely_pathogenic | 0.979 | pathogenic | -0.127 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | N |
| R/G | 0.945 | likely_pathogenic | 0.951 | pathogenic | -0.706 | Destabilizing | 1.0 | D | 0.635 | neutral | N | 0.49524449 | None | None | N |
| R/H | 0.6173 | likely_pathogenic | 0.6299 | pathogenic | -1.115 | Destabilizing | 1.0 | D | 0.769 | deleterious | N | 0.494049663 | None | None | N |
| R/I | 0.8634 | likely_pathogenic | 0.8731 | pathogenic | 0.444 | Stabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | N |
| R/K | 0.4097 | ambiguous | 0.4183 | ambiguous | -0.349 | Destabilizing | 0.998 | D | 0.597 | neutral | None | None | None | None | N |
| R/L | 0.7789 | likely_pathogenic | 0.7962 | pathogenic | 0.444 | Stabilizing | 1.0 | D | 0.635 | neutral | N | 0.44333639 | None | None | N |
| R/M | 0.8847 | likely_pathogenic | 0.897 | pathogenic | -0.189 | Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | N |
| R/N | 0.9742 | likely_pathogenic | 0.9791 | pathogenic | -0.173 | Destabilizing | 1.0 | D | 0.742 | deleterious | None | None | None | None | N |
| R/P | 0.8818 | likely_pathogenic | 0.8974 | pathogenic | 0.187 | Stabilizing | 1.0 | D | 0.713 | prob.delet. | N | 0.404877187 | None | None | N |
| R/Q | 0.498 | ambiguous | 0.5236 | ambiguous | -0.162 | Destabilizing | 1.0 | D | 0.734 | prob.delet. | None | None | None | None | N |
| R/S | 0.9809 | likely_pathogenic | 0.9839 | pathogenic | -0.705 | Destabilizing | 1.0 | D | 0.692 | prob.neutral | N | 0.461214284 | None | None | N |
| R/T | 0.9408 | likely_pathogenic | 0.9514 | pathogenic | -0.369 | Destabilizing | 1.0 | D | 0.687 | prob.neutral | None | None | None | None | N |
| R/V | 0.8864 | likely_pathogenic | 0.8983 | pathogenic | 0.187 | Stabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | N |
| R/W | 0.8105 | likely_pathogenic | 0.8203 | pathogenic | 0.054 | Stabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | N |
| R/Y | 0.927 | likely_pathogenic | 0.9391 | pathogenic | 0.36 | Stabilizing | 1.0 | D | 0.728 | prob.delet. | 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.