Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2812 | 8659;8660;8661 | chr2:178770267;178770266;178770265 | chr2:179634994;179634993;179634992 |
| N2AB | 2812 | 8659;8660;8661 | chr2:178770267;178770266;178770265 | chr2:179634994;179634993;179634992 |
| N2A | 2812 | 8659;8660;8661 | chr2:178770267;178770266;178770265 | chr2:179634994;179634993;179634992 |
| N2B | 2766 | 8521;8522;8523 | chr2:178770267;178770266;178770265 | chr2:179634994;179634993;179634992 |
| Novex-1 | 2766 | 8521;8522;8523 | chr2:178770267;178770266;178770265 | chr2:179634994;179634993;179634992 |
| Novex-2 | 2766 | 8521;8522;8523 | chr2:178770267;178770266;178770265 | chr2:179634994;179634993;179634992 |
| Novex-3 | 2812 | 8659;8660;8661 | chr2:178770267;178770266;178770265 | chr2:179634994;179634993;179634992 |
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/I | None | None | 0.78 | N | 0.613 | 0.195 | 0.402614778071 | gnomAD-4.0.0 | 1.36812E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79859E-06 | 0 | 0 |
| V/L | rs146636599  |
-0.254 | 0.78 | N | 0.597 | 0.16 | None | gnomAD-2.1.1 | 9.56E-05 | None | None | None | None | N | None | 4.00609E-04 | 0 | None | 0 | 7.02247E-04 | None | 6.53E-05 | None | 0 | 0 | 1.38735E-04 |
| V/L | rs146636599 |
-0.254 | 0.78 | N | 0.597 | 0.16 | None | gnomAD-3.1.2 | 1.44575E-04 | None | None | None | None | N | None | 3.86156E-04 | 0 | 0 | 0 | 5.77812E-04 | None | 0 | 0 | 0 | 2.06954E-04 | 9.56023E-04 |
| V/L | rs146636599 |
-0.254 | 0.78 | N | 0.597 | 0.16 | None | gnomAD-4.0.0 | 4.39862E-05 | None | None | None | None | N | None | 2.79866E-04 | 0 | None | 0 | 6.01685E-04 | None | 0 | 0 | 3.38979E-06 | 7.68504E-05 | 1.91975E-04 |
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 | 0.177 | likely_benign | 0.2201 | benign | -1.667 | Destabilizing | 0.004 | N | 0.27 | neutral | N | 0.386289488 | None | None | N |
| V/C | 0.8618 | likely_pathogenic | 0.8916 | pathogenic | -1.201 | Destabilizing | 0.999 | D | 0.773 | deleterious | None | None | None | None | N |
| V/D | 0.9801 | likely_pathogenic | 0.9786 | pathogenic | -1.628 | Destabilizing | 0.984 | D | 0.828 | deleterious | D | 0.562238531 | None | None | N |
| V/E | 0.9498 | likely_pathogenic | 0.9478 | pathogenic | -1.492 | Destabilizing | 0.976 | D | 0.771 | deleterious | None | None | None | None | N |
| V/F | 0.7129 | likely_pathogenic | 0.7376 | pathogenic | -1.007 | Destabilizing | 0.995 | D | 0.817 | deleterious | N | 0.518109708 | None | None | N |
| V/G | 0.669 | likely_pathogenic | 0.7228 | pathogenic | -2.116 | Highly Destabilizing | 0.811 | D | 0.725 | prob.delet. | N | 0.462052036 | None | None | N |
| V/H | 0.984 | likely_pathogenic | 0.9858 | pathogenic | -1.604 | Destabilizing | 0.999 | D | 0.819 | deleterious | None | None | None | None | N |
| V/I | 0.1302 | likely_benign | 0.1407 | benign | -0.47 | Destabilizing | 0.78 | D | 0.613 | neutral | N | 0.460434032 | None | None | N |
| V/K | 0.973 | likely_pathogenic | 0.9671 | pathogenic | -1.416 | Destabilizing | 0.976 | D | 0.779 | deleterious | None | None | None | None | N |
| V/L | 0.6139 | likely_pathogenic | 0.6727 | pathogenic | -0.47 | Destabilizing | 0.78 | D | 0.597 | neutral | N | 0.455520477 | None | None | N |
| V/M | 0.4381 | ambiguous | 0.4779 | ambiguous | -0.474 | Destabilizing | 0.996 | D | 0.684 | prob.neutral | None | None | None | None | N |
| V/N | 0.9418 | likely_pathogenic | 0.9504 | pathogenic | -1.5 | Destabilizing | 0.988 | D | 0.839 | deleterious | None | None | None | None | N |
| V/P | 0.9811 | likely_pathogenic | 0.9856 | pathogenic | -0.837 | Destabilizing | 0.988 | D | 0.791 | deleterious | None | None | None | None | N |
| V/Q | 0.9449 | likely_pathogenic | 0.9486 | pathogenic | -1.455 | Destabilizing | 0.988 | D | 0.801 | deleterious | None | None | None | None | N |
| V/R | 0.9571 | likely_pathogenic | 0.9496 | pathogenic | -1.121 | Destabilizing | 0.988 | D | 0.841 | deleterious | None | None | None | None | N |
| V/S | 0.6279 | likely_pathogenic | 0.6899 | pathogenic | -2.115 | Highly Destabilizing | 0.851 | D | 0.7 | prob.neutral | None | None | None | None | N |
| V/T | 0.379 | ambiguous | 0.4281 | ambiguous | -1.835 | Destabilizing | 0.919 | D | 0.663 | neutral | None | None | None | None | N |
| V/W | 0.9951 | likely_pathogenic | 0.9957 | pathogenic | -1.327 | Destabilizing | 0.999 | D | 0.819 | deleterious | None | None | None | None | N |
| V/Y | 0.9684 | likely_pathogenic | 0.973 | pathogenic | -0.966 | Destabilizing | 0.996 | D | 0.789 | deleterious | 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.