Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15731 | 47416;47417;47418 | chr2:178618267;178618266;178618265 | chr2:179482994;179482993;179482992 |
| N2AB | 14090 | 42493;42494;42495 | chr2:178618267;178618266;178618265 | chr2:179482994;179482993;179482992 |
| N2A | 13163 | 39712;39713;39714 | chr2:178618267;178618266;178618265 | chr2:179482994;179482993;179482992 |
| N2B | 6666 | 20221;20222;20223 | chr2:178618267;178618266;178618265 | chr2:179482994;179482993;179482992 |
| Novex-1 | 6791 | 20596;20597;20598 | chr2:178618267;178618266;178618265 | chr2:179482994;179482993;179482992 |
| Novex-2 | 6858 | 20797;20798;20799 | chr2:178618267;178618266;178618265 | chr2:179482994;179482993;179482992 |
| 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/C | rs72677231  |
-1.46 | 1.0 | D | 0.811 | 0.56 | None | gnomAD-2.1.1 | 2.33307E-03 | None | None | None | None | N | None | 9.51514E-04 | 2.49278E-03 | None | 3.19582E-03 | 0 | None | 4.24892E-04 | None | 6.79674E-04 | 3.63046E-03 | 2.1103E-03 |
| R/C | rs72677231 |
-1.46 | 1.0 | D | 0.811 | 0.56 | None | gnomAD-3.1.2 | 2.24522E-03 | None | None | None | None | N | None | 9.65997E-04 | 2.03653E-03 | 0 | 3.17003E-03 | 0 | None | 2.82805E-04 | 0 | 3.71167E-03 | 4.14422E-04 | 9.58773E-04 |
| R/C | rs72677231 |
-1.46 | 1.0 | D | 0.811 | 0.56 | None | 1000 genomes | 1.39776E-03 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 7E-03 | None | None | None | 0 | None |
| R/C | rs72677231 |
-1.46 | 1.0 | D | 0.811 | 0.56 | None | gnomAD-4.0.0 | 3.39985E-03 | None | None | None | None | N | None | 7.60751E-04 | 2.23646E-03 | None | 3.24807E-03 | 0 | None | 5.93769E-04 | 1.4881E-03 | 4.18607E-03 | 4.94234E-04 | 2.69188E-03 |
| R/H | rs373613871 |
-2.0 | 1.0 | D | 0.829 | 0.495 | None | gnomAD-2.1.1 | 3.63E-05 | None | None | None | None | N | None | 1.94124E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 5.35E-05 | 0 |
| R/H | rs373613871 |
-2.0 | 1.0 | D | 0.829 | 0.495 | None | gnomAD-3.1.2 | 3.95E-05 | None | None | None | None | N | None | 7.24E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.95E-05 | 2.07297E-04 | 0 |
| R/H | rs373613871 |
-2.0 | 1.0 | D | 0.829 | 0.495 | None | 1000 genomes | 3.99361E-04 | None | None | None | None | N | None | 1.5E-03 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/H | rs373613871 |
-2.0 | 1.0 | D | 0.829 | 0.495 | None | gnomAD-4.0.0 | 2.04618E-05 | None | None | None | None | N | None | 8.00726E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.12018E-05 | 2.19664E-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 | 0.983 | likely_pathogenic | 0.9896 | pathogenic | -1.692 | Destabilizing | 0.999 | D | 0.657 | neutral | None | None | None | None | N |
| R/C | 0.7844 | likely_pathogenic | 0.8343 | pathogenic | -1.656 | Destabilizing | 1.0 | D | 0.811 | deleterious | D | 0.746107466 | None | None | N |
| R/D | 0.9985 | likely_pathogenic | 0.999 | pathogenic | -0.847 | Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | N |
| R/E | 0.9781 | likely_pathogenic | 0.9858 | pathogenic | -0.648 | Destabilizing | 0.999 | D | 0.707 | prob.neutral | None | None | None | None | N |
| R/F | 0.9926 | likely_pathogenic | 0.9957 | pathogenic | -0.914 | Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | N |
| R/G | 0.9816 | likely_pathogenic | 0.9885 | pathogenic | -2.014 | Highly Destabilizing | 1.0 | D | 0.753 | deleterious | D | 0.778557598 | None | None | N |
| R/H | 0.6603 | likely_pathogenic | 0.7469 | pathogenic | -2.002 | Highly Destabilizing | 1.0 | D | 0.829 | deleterious | D | 0.698097456 | None | None | N |
| R/I | 0.9729 | likely_pathogenic | 0.9808 | pathogenic | -0.771 | Destabilizing | 1.0 | D | 0.83 | deleterious | None | None | None | None | N |
| R/K | 0.6282 | likely_pathogenic | 0.6804 | pathogenic | -1.263 | Destabilizing | 0.998 | D | 0.679 | prob.neutral | None | None | None | None | N |
| R/L | 0.9471 | likely_pathogenic | 0.9639 | pathogenic | -0.771 | Destabilizing | 1.0 | D | 0.753 | deleterious | D | 0.687936201 | None | None | N |
| R/M | 0.9805 | likely_pathogenic | 0.9885 | pathogenic | -1.324 | Destabilizing | 1.0 | D | 0.813 | deleterious | None | None | None | None | N |
| R/N | 0.9945 | likely_pathogenic | 0.9967 | pathogenic | -1.149 | Destabilizing | 1.0 | D | 0.798 | deleterious | None | None | None | None | N |
| R/P | 0.9994 | likely_pathogenic | 0.9996 | pathogenic | -1.066 | Destabilizing | 1.0 | D | 0.813 | deleterious | D | 0.779848618 | None | None | N |
| R/Q | 0.6246 | likely_pathogenic | 0.7063 | pathogenic | -0.978 | Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | N |
| R/S | 0.9886 | likely_pathogenic | 0.9935 | pathogenic | -1.925 | Destabilizing | 1.0 | D | 0.753 | deleterious | D | 0.691806597 | None | None | N |
| R/T | 0.9851 | likely_pathogenic | 0.9901 | pathogenic | -1.535 | Destabilizing | 1.0 | D | 0.758 | deleterious | None | None | None | None | N |
| R/V | 0.9723 | likely_pathogenic | 0.9825 | pathogenic | -1.066 | Destabilizing | 1.0 | D | 0.809 | deleterious | None | None | None | None | N |
| R/W | 0.919 | likely_pathogenic | 0.9494 | pathogenic | -0.549 | Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | N |
| R/Y | 0.9791 | likely_pathogenic | 0.9899 | pathogenic | -0.367 | Destabilizing | 1.0 | D | 0.839 | 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.