Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16827 | 50704;50705;50706 | chr2:178611830;178611829;178611828 | chr2:179476557;179476556;179476555 |
| N2AB | 15186 | 45781;45782;45783 | chr2:178611830;178611829;178611828 | chr2:179476557;179476556;179476555 |
| N2A | 14259 | 43000;43001;43002 | chr2:178611830;178611829;178611828 | chr2:179476557;179476556;179476555 |
| N2B | 7762 | 23509;23510;23511 | chr2:178611830;178611829;178611828 | chr2:179476557;179476556;179476555 |
| Novex-1 | 7887 | 23884;23885;23886 | chr2:178611830;178611829;178611828 | chr2:179476557;179476556;179476555 |
| Novex-2 | 7954 | 24085;24086;24087 | chr2:178611830;178611829;178611828 | chr2:179476557;179476556;179476555 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/Q | rs138896856  |
-0.982 | 0.992 | N | 0.661 | 0.278 | None | gnomAD-2.1.1 | 1.57554E-04 | None | None | None | None | N | None | 4.13805E-04 | 1.98424E-04 | None | 0 | 0 | None | 3.27161E-04 | None | 4E-04 | 5.49E-05 | 0 |
| R/Q | rs138896856 |
-0.982 | 0.992 | N | 0.661 | 0.278 | None | gnomAD-3.1.2 | 1.51336E-04 | None | None | None | None | N | None | 1.44809E-04 | 6.56E-05 | 0 | 0 | 0 | None | 4.70898E-04 | 0 | 0 | 2.27743E-03 | 0 |
| R/Q | rs138896856 |
-0.982 | 0.992 | N | 0.661 | 0.278 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/Q | rs138896856 |
-0.982 | 0.992 | N | 0.661 | 0.278 | None | gnomAD-4.0.0 | 1.07257E-04 | None | None | None | None | N | None | 2.53435E-04 | 1.33453E-04 | None | 0 | 2.23584E-05 | None | 6.56147E-04 | 0 | 4.49421E-05 | 4.61417E-04 | 1.28115E-04 |
| R/W | rs727503620 |
-0.496 | 1.0 | D | 0.612 | 0.525 | None | gnomAD-2.1.1 | 1.43E-05 | None | None | None | None | N | None | 4.14E-05 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 1.57E-05 | 0 |
| R/W | rs727503620 |
-0.496 | 1.0 | D | 0.612 | 0.525 | None | 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 |
| R/W | rs727503620 |
-0.496 | 1.0 | D | 0.612 | 0.525 | None | gnomAD-4.0.0 | 1.30211E-05 | None | None | None | None | N | None | 6.68235E-05 | 0 | None | 0 | 0 | None | 0 | 3.29489E-04 | 7.63163E-06 | 4.39425E-05 | 1.602E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.8382 | likely_pathogenic | 0.804 | pathogenic | -1.263 | Destabilizing | 0.579 | D | 0.426 | neutral | None | None | None | None | N |
| R/C | 0.372 | ambiguous | 0.3037 | benign | -1.345 | Destabilizing | 0.046 | N | 0.517 | neutral | None | None | None | None | N |
| R/D | 0.9879 | likely_pathogenic | 0.9834 | pathogenic | -0.528 | Destabilizing | 0.939 | D | 0.561 | neutral | None | None | None | None | N |
| R/E | 0.9079 | likely_pathogenic | 0.887 | pathogenic | -0.35 | Destabilizing | 0.939 | D | 0.613 | neutral | None | None | None | None | N |
| R/F | 0.895 | likely_pathogenic | 0.8807 | pathogenic | -0.68 | Destabilizing | 0.997 | D | 0.633 | neutral | None | None | None | None | N |
| R/G | 0.8637 | likely_pathogenic | 0.8078 | pathogenic | -1.62 | Destabilizing | 0.924 | D | 0.554 | neutral | D | 0.617737264 | None | None | N |
| R/H | 0.3783 | ambiguous | 0.3416 | ambiguous | -1.648 | Destabilizing | 0.997 | D | 0.618 | neutral | None | None | None | None | N |
| R/I | 0.7736 | likely_pathogenic | 0.7471 | pathogenic | -0.264 | Destabilizing | 0.991 | D | 0.635 | neutral | None | None | None | None | N |
| R/K | 0.3188 | likely_benign | 0.2592 | benign | -1.305 | Destabilizing | 0.863 | D | 0.619 | neutral | None | None | None | None | N |
| R/L | 0.6207 | likely_pathogenic | 0.5363 | ambiguous | -0.264 | Destabilizing | 0.967 | D | 0.578 | neutral | N | 0.483750351 | None | None | N |
| R/M | 0.7255 | likely_pathogenic | 0.6412 | pathogenic | -0.71 | Destabilizing | 0.997 | D | 0.607 | neutral | None | None | None | None | N |
| R/N | 0.9581 | likely_pathogenic | 0.9459 | pathogenic | -0.978 | Destabilizing | 0.939 | D | 0.605 | neutral | None | None | None | None | N |
| R/P | 0.9981 | likely_pathogenic | 0.997 | pathogenic | -0.58 | Destabilizing | 0.995 | D | 0.636 | neutral | D | 0.618518793 | None | None | N |
| R/Q | 0.3246 | likely_benign | 0.2779 | benign | -0.939 | Destabilizing | 0.992 | D | 0.661 | neutral | N | 0.512492873 | None | None | N |
| R/S | 0.8817 | likely_pathogenic | 0.8551 | pathogenic | -1.765 | Destabilizing | 0.2 | N | 0.321 | neutral | None | None | None | None | N |
| R/T | 0.7989 | likely_pathogenic | 0.7566 | pathogenic | -1.386 | Destabilizing | 0.759 | D | 0.564 | neutral | None | None | None | None | N |
| R/V | 0.7895 | likely_pathogenic | 0.7491 | pathogenic | -0.58 | Destabilizing | 0.939 | D | 0.551 | neutral | None | None | None | None | N |
| R/W | 0.66 | likely_pathogenic | 0.6063 | pathogenic | -0.261 | Destabilizing | 1.0 | D | 0.612 | neutral | D | 0.554595243 | None | None | N |
| R/Y | 0.8394 | likely_pathogenic | 0.8077 | pathogenic | -0.029 | Destabilizing | 0.997 | D | 0.629 | 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.