Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32145 | 96658;96659;96660 | chr2:178543540;178543539;178543538 | chr2:179408267;179408266;179408265 |
| N2AB | 30504 | 91735;91736;91737 | chr2:178543540;178543539;178543538 | chr2:179408267;179408266;179408265 |
| N2A | 29577 | 88954;88955;88956 | chr2:178543540;178543539;178543538 | chr2:179408267;179408266;179408265 |
| N2B | 23080 | 69463;69464;69465 | chr2:178543540;178543539;178543538 | chr2:179408267;179408266;179408265 |
| Novex-1 | 23205 | 69838;69839;69840 | chr2:178543540;178543539;178543538 | chr2:179408267;179408266;179408265 |
| Novex-2 | 23272 | 70039;70040;70041 | chr2:178543540;178543539;178543538 | chr2:179408267;179408266;179408265 |
| 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 | rs878907981  |
-1.616 | 1.0 | N | 0.886 | 0.498 | None | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 1.14837E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/C | rs878907981 |
-1.616 | 1.0 | N | 0.886 | 0.498 | 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/C | rs878907981 |
-1.616 | 1.0 | N | 0.886 | 0.498 | None | gnomAD-4.0.0 | 5.58189E-06 | None | None | None | None | N | None | 4.00481E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 4.23839E-06 | 1.09815E-05 | 0 |
| R/H | rs759948951 |
-2.274 | 1.0 | N | 0.761 | 0.553 | 0.38225645794 | gnomAD-2.1.1 | 1.62E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.68E-05 | 1.66778E-04 |
| R/H | rs759948951 |
-2.274 | 1.0 | N | 0.761 | 0.553 | 0.38225645794 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 5.88E-05 | 0 | 0 |
| R/H | rs759948951 |
-2.274 | 1.0 | N | 0.761 | 0.553 | 0.38225645794 | gnomAD-4.0.0 | 1.30229E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.23135E-05 | None | 0 | 0 | 1.52582E-05 | 1.09827E-05 | 1.60133E-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 | 0.988 | likely_pathogenic | 0.9894 | pathogenic | -2.115 | Highly Destabilizing | 1.0 | D | 0.55 | neutral | None | None | None | None | N |
| R/C | 0.8258 | likely_pathogenic | 0.7901 | pathogenic | -1.896 | Destabilizing | 1.0 | D | 0.886 | deleterious | N | 0.472030802 | None | None | N |
| R/D | 0.9982 | likely_pathogenic | 0.9984 | pathogenic | -1.062 | Destabilizing | 1.0 | D | 0.865 | deleterious | None | None | None | None | N |
| R/E | 0.9804 | likely_pathogenic | 0.982 | pathogenic | -0.84 | Destabilizing | 1.0 | D | 0.548 | neutral | None | None | None | None | N |
| R/F | 0.9947 | likely_pathogenic | 0.9939 | pathogenic | -1.221 | Destabilizing | 1.0 | D | 0.889 | deleterious | None | None | None | None | N |
| R/G | 0.9697 | likely_pathogenic | 0.9727 | pathogenic | -2.46 | Highly Destabilizing | 1.0 | D | 0.783 | deleterious | N | 0.485931548 | None | None | N |
| R/H | 0.7837 | likely_pathogenic | 0.7579 | pathogenic | -2.187 | Highly Destabilizing | 1.0 | D | 0.761 | deleterious | N | 0.497959417 | None | None | N |
| R/I | 0.9893 | likely_pathogenic | 0.9903 | pathogenic | -1.103 | Destabilizing | 1.0 | D | 0.901 | deleterious | None | None | None | None | N |
| R/K | 0.454 | ambiguous | 0.4346 | ambiguous | -1.353 | Destabilizing | 0.998 | D | 0.45 | neutral | None | None | None | None | N |
| R/L | 0.965 | likely_pathogenic | 0.9598 | pathogenic | -1.103 | Destabilizing | 1.0 | D | 0.783 | deleterious | N | 0.48319607 | None | None | N |
| R/M | 0.9719 | likely_pathogenic | 0.9721 | pathogenic | -1.551 | Destabilizing | 1.0 | D | 0.858 | deleterious | None | None | None | None | N |
| R/N | 0.9954 | likely_pathogenic | 0.9957 | pathogenic | -1.406 | Destabilizing | 1.0 | D | 0.698 | prob.neutral | None | None | None | None | N |
| R/P | 0.9991 | likely_pathogenic | 0.9991 | pathogenic | -1.431 | Destabilizing | 1.0 | D | 0.872 | deleterious | N | 0.509062233 | None | None | N |
| R/Q | 0.6328 | likely_pathogenic | 0.6198 | pathogenic | -1.247 | Destabilizing | 1.0 | D | 0.68 | prob.neutral | None | None | None | None | N |
| R/S | 0.9953 | likely_pathogenic | 0.9956 | pathogenic | -2.3 | Highly Destabilizing | 1.0 | D | 0.783 | deleterious | N | 0.471533369 | None | None | N |
| R/T | 0.992 | likely_pathogenic | 0.9932 | pathogenic | -1.866 | Destabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | N |
| R/V | 0.9873 | likely_pathogenic | 0.9886 | pathogenic | -1.431 | Destabilizing | 1.0 | D | 0.881 | deleterious | None | None | None | None | N |
| R/W | 0.928 | likely_pathogenic | 0.9045 | pathogenic | -0.719 | Destabilizing | 1.0 | D | 0.877 | deleterious | None | None | None | None | N |
| R/Y | 0.9736 | likely_pathogenic | 0.9683 | pathogenic | -0.627 | Destabilizing | 1.0 | D | 0.901 | 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.