Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14336 | 43231;43232;43233 | chr2:178633267;178633266;178633265 | chr2:179497994;179497993;179497992 |
| N2AB | 12695 | 38308;38309;38310 | chr2:178633267;178633266;178633265 | chr2:179497994;179497993;179497992 |
| N2A | 11768 | 35527;35528;35529 | chr2:178633267;178633266;178633265 | chr2:179497994;179497993;179497992 |
| N2B | 5271 | 16036;16037;16038 | chr2:178633267;178633266;178633265 | chr2:179497994;179497993;179497992 |
| Novex-1 | 5396 | 16411;16412;16413 | chr2:178633267;178633266;178633265 | chr2:179497994;179497993;179497992 |
| Novex-2 | 5463 | 16612;16613;16614 | chr2:178633267;178633266;178633265 | chr2:179497994;179497993;179497992 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/T | rs2060026775  |
None | 0.071 | D | 0.266 | 0.347 | 0.221734844693 | gnomAD-4.0.0 | 6.36914E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.11111E-04 | None | 0 | 0 | 0 | 0 | 0 |
| A/V | rs749230107 |
-0.084 | 0.841 | N | 0.51 | 0.33 | 0.30921473904 | gnomAD-2.1.1 | 2.01E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.79486E-04 | None | 0 | None | 0 | 0 | 0 |
| A/V | rs749230107 |
-0.084 | 0.841 | N | 0.51 | 0.33 | 0.30921473904 | gnomAD-4.0.0 | 1.75153E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 3.05539E-04 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.8083 | likely_pathogenic | 0.7202 | pathogenic | -0.823 | Destabilizing | 0.999 | D | 0.799 | deleterious | None | None | None | None | N |
| A/D | 0.9922 | likely_pathogenic | 0.99 | pathogenic | -2.449 | Highly Destabilizing | 0.974 | D | 0.899 | deleterious | D | 0.639867921 | None | None | N |
| A/E | 0.9822 | likely_pathogenic | 0.9786 | pathogenic | -2.245 | Highly Destabilizing | 0.98 | D | 0.823 | deleterious | None | None | None | None | N |
| A/F | 0.9628 | likely_pathogenic | 0.9364 | pathogenic | -0.819 | Destabilizing | 0.99 | D | 0.91 | deleterious | None | None | None | None | N |
| A/G | 0.5336 | ambiguous | 0.4925 | ambiguous | -1.611 | Destabilizing | 0.914 | D | 0.483 | neutral | D | 0.639207399 | None | None | N |
| A/H | 0.9927 | likely_pathogenic | 0.9892 | pathogenic | -2.168 | Highly Destabilizing | 0.999 | D | 0.906 | deleterious | None | None | None | None | N |
| A/I | 0.7858 | likely_pathogenic | 0.6422 | pathogenic | 0.15 | Stabilizing | 0.98 | D | 0.867 | deleterious | None | None | None | None | N |
| A/K | 0.9926 | likely_pathogenic | 0.9904 | pathogenic | -1.299 | Destabilizing | 0.98 | D | 0.839 | deleterious | None | None | None | None | N |
| A/L | 0.7431 | likely_pathogenic | 0.6606 | pathogenic | 0.15 | Stabilizing | 0.875 | D | 0.669 | prob.neutral | None | None | None | None | N |
| A/M | 0.8774 | likely_pathogenic | 0.8034 | pathogenic | 0.163 | Stabilizing | 0.999 | D | 0.844 | deleterious | None | None | None | None | N |
| A/N | 0.9845 | likely_pathogenic | 0.9783 | pathogenic | -1.549 | Destabilizing | 0.98 | D | 0.887 | deleterious | None | None | None | None | N |
| A/P | 0.9658 | likely_pathogenic | 0.9579 | pathogenic | -0.237 | Destabilizing | 0.987 | D | 0.871 | deleterious | D | 0.639867921 | None | None | N |
| A/Q | 0.9738 | likely_pathogenic | 0.9663 | pathogenic | -1.359 | Destabilizing | 0.99 | D | 0.878 | deleterious | None | None | None | None | N |
| A/R | 0.9742 | likely_pathogenic | 0.9711 | pathogenic | -1.377 | Destabilizing | 0.98 | D | 0.866 | deleterious | None | None | None | None | N |
| A/S | 0.4365 | ambiguous | 0.3847 | ambiguous | -1.919 | Destabilizing | 0.841 | D | 0.509 | neutral | D | 0.639062378 | None | None | N |
| A/T | 0.5097 | ambiguous | 0.3774 | ambiguous | -1.597 | Destabilizing | 0.071 | N | 0.266 | neutral | D | 0.637059924 | None | None | N |
| A/V | 0.427 | ambiguous | 0.2824 | benign | -0.237 | Destabilizing | 0.841 | D | 0.51 | neutral | N | 0.447759192 | None | None | N |
| A/W | 0.9977 | likely_pathogenic | 0.9957 | pathogenic | -1.687 | Destabilizing | 0.999 | D | 0.91 | deleterious | None | None | None | None | N |
| A/Y | 0.9898 | likely_pathogenic | 0.9832 | pathogenic | -1.084 | Destabilizing | 0.999 | D | 0.917 | 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.