Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1891 | 5896;5897;5898 | chr2:178776193;178776192;178776191 | chr2:179640920;179640919;179640918 |
| N2AB | 1891 | 5896;5897;5898 | chr2:178776193;178776192;178776191 | chr2:179640920;179640919;179640918 |
| N2A | 1891 | 5896;5897;5898 | chr2:178776193;178776192;178776191 | chr2:179640920;179640919;179640918 |
| N2B | 1845 | 5758;5759;5760 | chr2:178776193;178776192;178776191 | chr2:179640920;179640919;179640918 |
| Novex-1 | 1845 | 5758;5759;5760 | chr2:178776193;178776192;178776191 | chr2:179640920;179640919;179640918 |
| Novex-2 | 1845 | 5758;5759;5760 | chr2:178776193;178776192;178776191 | chr2:179640920;179640919;179640918 |
| Novex-3 | 1891 | 5896;5897;5898 | chr2:178776193;178776192;178776191 | chr2:179640920;179640919;179640918 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/C | rs547305291  |
-0.254 | 1.0 | D | 0.799 | 0.707 | 0.604789236398 | gnomAD-2.1.1 | 4.38E-05 | None | None | None | None | N | None | 0 | 2.89E-05 | None | 0 | 0 | None | 3.26627E-04 | None | 0 | 0 | 0 |
| Y/C | rs547305291 |
-0.254 | 1.0 | D | 0.799 | 0.707 | 0.604789236398 | gnomAD-3.1.2 | 3.28E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 1.0352E-03 | 0 |
| Y/C | rs547305291 |
-0.254 | 1.0 | D | 0.799 | 0.707 | 0.604789236398 | 1000 genomes | 5.99042E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 3.1E-03 | None |
| Y/C | rs547305291 |
-0.254 | 1.0 | D | 0.799 | 0.707 | 0.604789236398 | gnomAD-4.0.0 | 3.65513E-05 | None | None | None | None | N | None | 0 | 1.66622E-05 | None | 0 | 0 | None | 0 | 0 | 2.54237E-06 | 5.92859E-04 | 1.59974E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.7857 | likely_pathogenic | 0.7591 | pathogenic | -0.915 | Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | N |
| Y/C | 0.445 | ambiguous | 0.4308 | ambiguous | 0.097 | Stabilizing | 1.0 | D | 0.799 | deleterious | D | 0.559198388 | None | None | N |
| Y/D | 0.7501 | likely_pathogenic | 0.6812 | pathogenic | 0.333 | Stabilizing | 1.0 | D | 0.82 | deleterious | N | 0.501719533 | None | None | N |
| Y/E | 0.895 | likely_pathogenic | 0.8672 | pathogenic | 0.322 | Stabilizing | 1.0 | D | 0.811 | deleterious | None | None | None | None | N |
| Y/F | 0.129 | likely_benign | 0.1267 | benign | -0.489 | Destabilizing | 0.999 | D | 0.667 | neutral | N | 0.503016513 | None | None | N |
| Y/G | 0.727 | likely_pathogenic | 0.6947 | pathogenic | -1.121 | Destabilizing | 1.0 | D | 0.806 | deleterious | None | None | None | None | N |
| Y/H | 0.4346 | ambiguous | 0.3932 | ambiguous | 0.019 | Stabilizing | 1.0 | D | 0.729 | prob.delet. | N | 0.510672257 | None | None | N |
| Y/I | 0.8285 | likely_pathogenic | 0.8032 | pathogenic | -0.374 | Destabilizing | 1.0 | D | 0.782 | deleterious | None | None | None | None | N |
| Y/K | 0.9129 | likely_pathogenic | 0.8938 | pathogenic | -0.044 | Destabilizing | 1.0 | D | 0.809 | deleterious | None | None | None | None | N |
| Y/L | 0.776 | likely_pathogenic | 0.7536 | pathogenic | -0.374 | Destabilizing | 0.999 | D | 0.76 | deleterious | None | None | None | None | N |
| Y/M | 0.8276 | likely_pathogenic | 0.807 | pathogenic | -0.196 | Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | N |
| Y/N | 0.3709 | ambiguous | 0.3229 | benign | -0.282 | Destabilizing | 1.0 | D | 0.818 | deleterious | N | 0.470458649 | None | None | N |
| Y/P | 0.9619 | likely_pathogenic | 0.9576 | pathogenic | -0.538 | Destabilizing | 1.0 | D | 0.815 | deleterious | None | None | None | None | N |
| Y/Q | 0.8095 | likely_pathogenic | 0.7761 | pathogenic | -0.251 | Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | N |
| Y/R | 0.8286 | likely_pathogenic | 0.797 | pathogenic | 0.264 | Stabilizing | 1.0 | D | 0.817 | deleterious | None | None | None | None | N |
| Y/S | 0.4022 | ambiguous | 0.3586 | ambiguous | -0.616 | Destabilizing | 1.0 | D | 0.808 | deleterious | N | 0.465151884 | None | None | N |
| Y/T | 0.6969 | likely_pathogenic | 0.6602 | pathogenic | -0.536 | Destabilizing | 1.0 | D | 0.812 | deleterious | None | None | None | None | N |
| Y/V | 0.7137 | likely_pathogenic | 0.6844 | pathogenic | -0.538 | Destabilizing | 1.0 | D | 0.762 | deleterious | None | None | None | None | N |
| Y/W | 0.6256 | likely_pathogenic | 0.6219 | pathogenic | -0.569 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | 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.