Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16533 | 49822;49823;49824 | chr2:178613212;178613211;178613210 | chr2:179477939;179477938;179477937 |
| N2AB | 14892 | 44899;44900;44901 | chr2:178613212;178613211;178613210 | chr2:179477939;179477938;179477937 |
| N2A | 13965 | 42118;42119;42120 | chr2:178613212;178613211;178613210 | chr2:179477939;179477938;179477937 |
| N2B | 7468 | 22627;22628;22629 | chr2:178613212;178613211;178613210 | chr2:179477939;179477938;179477937 |
| Novex-1 | 7593 | 23002;23003;23004 | chr2:178613212;178613211;178613210 | chr2:179477939;179477938;179477937 |
| Novex-2 | 7660 | 23203;23204;23205 | chr2:178613212;178613211;178613210 | chr2:179477939;179477938;179477937 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/S | rs756975730  |
-1.406 | 0.817 | N | 0.432 | 0.224 | 0.17948927462 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 6.48E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| P/S | rs756975730 |
-1.406 | 0.817 | N | 0.432 | 0.224 | 0.17948927462 | gnomAD-3.1.2 | 6.59E-06 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/S | rs756975730 |
-1.406 | 0.817 | N | 0.432 | 0.224 | 0.17948927462 | gnomAD-4.0.0 | 5.58499E-06 | None | None | None | None | N | None | 2.6753E-05 | 0 | None | 0 | 2.24215E-05 | None | 0 | 1.64853E-04 | 4.24137E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.126 | likely_benign | 0.0927 | benign | -1.372 | Destabilizing | 0.911 | D | 0.645 | neutral | N | 0.46166703 | None | None | N |
| P/C | 0.7312 | likely_pathogenic | 0.5569 | ambiguous | -0.824 | Destabilizing | 1.0 | D | 0.821 | deleterious | None | None | None | None | N |
| P/D | 0.9279 | likely_pathogenic | 0.8011 | pathogenic | -1.202 | Destabilizing | 0.996 | D | 0.727 | prob.delet. | None | None | None | None | N |
| P/E | 0.7026 | likely_pathogenic | 0.4974 | ambiguous | -1.26 | Destabilizing | 0.996 | D | 0.715 | prob.delet. | None | None | None | None | N |
| P/F | 0.8009 | likely_pathogenic | 0.5937 | pathogenic | -1.244 | Destabilizing | 0.999 | D | 0.819 | deleterious | None | None | None | None | N |
| P/G | 0.7619 | likely_pathogenic | 0.5469 | ambiguous | -1.632 | Destabilizing | 0.985 | D | 0.749 | deleterious | None | None | None | None | N |
| P/H | 0.6272 | likely_pathogenic | 0.411 | ambiguous | -1.107 | Destabilizing | 1.0 | D | 0.817 | deleterious | N | 0.466294037 | None | None | N |
| P/I | 0.3389 | likely_benign | 0.2045 | benign | -0.782 | Destabilizing | 0.996 | D | 0.821 | deleterious | None | None | None | None | N |
| P/K | 0.7619 | likely_pathogenic | 0.5351 | ambiguous | -1.068 | Destabilizing | 0.996 | D | 0.728 | prob.delet. | None | None | None | None | N |
| P/L | 0.2156 | likely_benign | 0.1328 | benign | -0.782 | Destabilizing | 0.98 | D | 0.763 | deleterious | N | 0.413383433 | None | None | N |
| P/M | 0.4503 | ambiguous | 0.2917 | benign | -0.487 | Destabilizing | 1.0 | D | 0.819 | deleterious | None | None | None | None | N |
| P/N | 0.7874 | likely_pathogenic | 0.5776 | pathogenic | -0.733 | Destabilizing | 0.996 | D | 0.788 | deleterious | None | None | None | None | N |
| P/Q | 0.442 | ambiguous | 0.2777 | benign | -1.004 | Destabilizing | 0.998 | D | 0.771 | deleterious | None | None | None | None | N |
| P/R | 0.6347 | likely_pathogenic | 0.4075 | ambiguous | -0.442 | Destabilizing | 0.997 | D | 0.819 | deleterious | N | 0.460392683 | None | None | N |
| P/S | 0.3978 | ambiguous | 0.2519 | benign | -1.204 | Destabilizing | 0.817 | D | 0.432 | neutral | N | 0.468148019 | None | None | N |
| P/T | 0.2227 | likely_benign | 0.1346 | benign | -1.161 | Destabilizing | 0.4 | N | 0.442 | neutral | N | 0.447666488 | None | None | N |
| P/V | 0.2475 | likely_benign | 0.1558 | benign | -0.944 | Destabilizing | 0.985 | D | 0.754 | deleterious | None | None | None | None | N |
| P/W | 0.9327 | likely_pathogenic | 0.8091 | pathogenic | -1.339 | Destabilizing | 1.0 | D | 0.772 | deleterious | None | None | None | None | N |
| P/Y | 0.8338 | likely_pathogenic | 0.6445 | pathogenic | -1.085 | Destabilizing | 0.999 | D | 0.819 | 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.