Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28228 | 84907;84908;84909 | chr2:178561450;178561449;178561448 | chr2:179426177;179426176;179426175 |
| N2AB | 26587 | 79984;79985;79986 | chr2:178561450;178561449;178561448 | chr2:179426177;179426176;179426175 |
| N2A | 25660 | 77203;77204;77205 | chr2:178561450;178561449;178561448 | chr2:179426177;179426176;179426175 |
| N2B | 19163 | 57712;57713;57714 | chr2:178561450;178561449;178561448 | chr2:179426177;179426176;179426175 |
| Novex-1 | 19288 | 58087;58088;58089 | chr2:178561450;178561449;178561448 | chr2:179426177;179426176;179426175 |
| Novex-2 | 19355 | 58288;58289;58290 | chr2:178561450;178561449;178561448 | chr2:179426177;179426176;179426175 |
| 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 | rs776756769  |
-1.652 | 0.996 | D | 0.708 | 0.532 | 0.803072696312 | gnomAD-2.1.1 | 2.01E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 3.56E-05 | 0 |
| R/C | rs776756769 |
-1.652 | 0.996 | D | 0.708 | 0.532 | 0.803072696312 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/C | rs776756769 |
-1.652 | 0.996 | D | 0.708 | 0.532 | 0.803072696312 | gnomAD-4.0.0 | 9.29592E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.01713E-05 | 2.19568E-05 | 1.60097E-05 |
| R/H | rs768301442 |
-2.317 | 0.02 | D | 0.442 | 0.415 | 0.368743488249 | gnomAD-2.1.1 | 2.82E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.30727E-04 | None | 0 | 2.67E-05 | 0 |
| R/H | rs768301442 |
-2.317 | 0.02 | D | 0.442 | 0.415 | 0.368743488249 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/H | rs768301442 |
-2.317 | 0.02 | D | 0.442 | 0.415 | 0.368743488249 | gnomAD-4.0.0 | 2.41684E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.22876E-05 | None | 1.56255E-05 | 0 | 2.11901E-05 | 1.09786E-04 | 3.20184E-05 |
| R/P | rs768301442 |
-1.408 | 0.901 | D | 0.647 | 0.539 | 0.631991100555 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/P | rs768301442 |
-1.408 | 0.901 | D | 0.647 | 0.539 | 0.631991100555 | gnomAD-4.0.0 | 6.8421E-07 | None | None | None | None | N | None | 0 | 2.23644E-05 | None | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9841 | likely_pathogenic | 0.9829 | pathogenic | -1.958 | Destabilizing | 0.399 | N | 0.516 | neutral | None | None | None | None | N |
| R/C | 0.707 | likely_pathogenic | 0.6825 | pathogenic | -1.888 | Destabilizing | 0.996 | D | 0.708 | prob.delet. | D | 0.538602153 | None | None | N |
| R/D | 0.9986 | likely_pathogenic | 0.9986 | pathogenic | -0.997 | Destabilizing | 0.7 | D | 0.569 | neutral | None | None | None | None | N |
| R/E | 0.9764 | likely_pathogenic | 0.9733 | pathogenic | -0.771 | Destabilizing | 0.25 | N | 0.53 | neutral | None | None | None | None | N |
| R/F | 0.991 | likely_pathogenic | 0.9907 | pathogenic | -1.113 | Destabilizing | 0.7 | D | 0.72 | prob.delet. | None | None | None | None | N |
| R/G | 0.9846 | likely_pathogenic | 0.9826 | pathogenic | -2.315 | Highly Destabilizing | 0.561 | D | 0.526 | neutral | D | 0.549704969 | None | None | N |
| R/H | 0.5343 | ambiguous | 0.5251 | ambiguous | -2.112 | Highly Destabilizing | 0.02 | N | 0.442 | neutral | D | 0.549958458 | None | None | N |
| R/I | 0.9604 | likely_pathogenic | 0.9535 | pathogenic | -0.923 | Destabilizing | 0.826 | D | 0.707 | prob.neutral | None | None | None | None | N |
| R/K | 0.4458 | ambiguous | 0.3738 | ambiguous | -1.331 | Destabilizing | 0.215 | N | 0.6 | neutral | None | None | None | None | N |
| R/L | 0.9355 | likely_pathogenic | 0.9248 | pathogenic | -0.923 | Destabilizing | 0.817 | D | 0.535 | neutral | D | 0.523624997 | None | None | N |
| R/M | 0.9646 | likely_pathogenic | 0.9536 | pathogenic | -1.447 | Destabilizing | 0.982 | D | 0.595 | neutral | None | None | None | None | N |
| R/N | 0.9937 | likely_pathogenic | 0.9937 | pathogenic | -1.386 | Destabilizing | 0.25 | N | 0.511 | neutral | None | None | None | None | N |
| R/P | 0.9993 | likely_pathogenic | 0.9994 | pathogenic | -1.257 | Destabilizing | 0.901 | D | 0.647 | neutral | D | 0.550211948 | None | None | N |
| R/Q | 0.4846 | ambiguous | 0.4382 | ambiguous | -1.213 | Destabilizing | 0.7 | D | 0.526 | neutral | None | None | None | None | N |
| R/S | 0.9907 | likely_pathogenic | 0.9901 | pathogenic | -2.258 | Highly Destabilizing | 0.561 | D | 0.499 | neutral | N | 0.520076143 | None | None | N |
| R/T | 0.9792 | likely_pathogenic | 0.9752 | pathogenic | -1.815 | Destabilizing | 0.7 | D | 0.507 | neutral | None | None | None | None | N |
| R/V | 0.9648 | likely_pathogenic | 0.9581 | pathogenic | -1.257 | Destabilizing | 0.826 | D | 0.685 | prob.neutral | None | None | None | None | N |
| R/W | 0.8914 | likely_pathogenic | 0.8904 | pathogenic | -0.632 | Destabilizing | 0.982 | D | 0.692 | prob.neutral | None | None | None | None | N |
| R/Y | 0.9697 | likely_pathogenic | 0.9715 | pathogenic | -0.498 | Destabilizing | 0.539 | D | 0.641 | 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.