Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15458 | 46597;46598;46599 | chr2:178620045;178620044;178620043 | chr2:179484772;179484771;179484770 |
| N2AB | 13817 | 41674;41675;41676 | chr2:178620045;178620044;178620043 | chr2:179484772;179484771;179484770 |
| N2A | 12890 | 38893;38894;38895 | chr2:178620045;178620044;178620043 | chr2:179484772;179484771;179484770 |
| N2B | 6393 | 19402;19403;19404 | chr2:178620045;178620044;178620043 | chr2:179484772;179484771;179484770 |
| Novex-1 | 6518 | 19777;19778;19779 | chr2:178620045;178620044;178620043 | chr2:179484772;179484771;179484770 |
| Novex-2 | 6585 | 19978;19979;19980 | chr2:178620045;178620044;178620043 | chr2:179484772;179484771;179484770 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/R | rs2058036083  |
None | 1.0 | N | 0.819 | 0.578 | 0.840504651409 | gnomAD-3.1.2 | 6.59E-06 | None | None | None | None | N | None | 0 | 6.57E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| C/R | rs2058036083 |
None | 1.0 | N | 0.819 | 0.578 | 0.840504651409 | gnomAD-4.0.0 | 6.58588E-06 | None | None | None | None | N | None | 0 | 6.57289E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| C/Y | rs377564388 |
-0.822 | 1.0 | N | 0.824 | 0.473 | None | gnomAD-2.1.1 | 2.16E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 4.73E-05 | 0 |
| C/Y | rs377564388 |
-0.822 | 1.0 | N | 0.824 | 0.473 | None | gnomAD-3.1.2 | 1.98E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.42E-05 | 0 | 0 |
| C/Y | rs377564388 |
-0.822 | 1.0 | N | 0.824 | 0.473 | None | gnomAD-4.0.0 | 5.64553E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.71966E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/A | 0.4536 | ambiguous | 0.5468 | ambiguous | -1.798 | Destabilizing | 0.998 | D | 0.723 | prob.delet. | None | None | None | None | N |
| C/D | 0.8687 | likely_pathogenic | 0.8944 | pathogenic | -1.093 | Destabilizing | 1.0 | D | 0.815 | deleterious | None | None | None | None | N |
| C/E | 0.9415 | likely_pathogenic | 0.9613 | pathogenic | -0.947 | Destabilizing | 1.0 | D | 0.817 | deleterious | None | None | None | None | N |
| C/F | 0.5387 | ambiguous | 0.6493 | pathogenic | -1.157 | Destabilizing | 1.0 | D | 0.821 | deleterious | N | 0.50172032 | None | None | N |
| C/G | 0.2055 | likely_benign | 0.2156 | benign | -2.129 | Highly Destabilizing | 1.0 | D | 0.795 | deleterious | N | 0.320550302 | None | None | N |
| C/H | 0.8386 | likely_pathogenic | 0.8946 | pathogenic | -2.271 | Highly Destabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | None | N |
| C/I | 0.8803 | likely_pathogenic | 0.9389 | pathogenic | -0.932 | Destabilizing | 1.0 | D | 0.823 | deleterious | None | None | None | None | N |
| C/K | 0.9585 | likely_pathogenic | 0.9753 | pathogenic | -1.267 | Destabilizing | 1.0 | D | 0.812 | deleterious | None | None | None | None | N |
| C/L | 0.788 | likely_pathogenic | 0.8553 | pathogenic | -0.932 | Destabilizing | 0.999 | D | 0.727 | prob.delet. | None | None | None | None | N |
| C/M | 0.7753 | likely_pathogenic | 0.8496 | pathogenic | 0.064 | Stabilizing | 1.0 | D | 0.829 | deleterious | None | None | None | None | N |
| C/N | 0.6711 | likely_pathogenic | 0.7436 | pathogenic | -1.446 | Destabilizing | 1.0 | D | 0.818 | deleterious | None | None | None | None | N |
| C/P | 0.9971 | likely_pathogenic | 0.9979 | pathogenic | -1.196 | Destabilizing | 1.0 | D | 0.818 | deleterious | None | None | None | None | N |
| C/Q | 0.8592 | likely_pathogenic | 0.9141 | pathogenic | -1.263 | Destabilizing | 1.0 | D | 0.823 | deleterious | None | None | None | None | N |
| C/R | 0.8362 | likely_pathogenic | 0.8946 | pathogenic | -1.264 | Destabilizing | 1.0 | D | 0.819 | deleterious | N | 0.507483953 | None | None | N |
| C/S | 0.3323 | likely_benign | 0.3996 | ambiguous | -1.89 | Destabilizing | 1.0 | D | 0.793 | deleterious | N | 0.484042046 | None | None | N |
| C/T | 0.6254 | likely_pathogenic | 0.73 | pathogenic | -1.564 | Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | N |
| C/V | 0.7417 | likely_pathogenic | 0.8438 | pathogenic | -1.196 | Destabilizing | 0.999 | D | 0.771 | deleterious | None | None | None | None | N |
| C/W | 0.8544 | likely_pathogenic | 0.9053 | pathogenic | -1.308 | Destabilizing | 1.0 | D | 0.785 | deleterious | N | 0.501938569 | None | None | N |
| C/Y | 0.6798 | likely_pathogenic | 0.7713 | pathogenic | -1.228 | Destabilizing | 1.0 | D | 0.824 | deleterious | N | 0.50172032 | 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.