Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1588 | 4987;4988;4989 | chr2:178777201;178777200;178777199 | chr2:179641928;179641927;179641926 |
| N2AB | 1588 | 4987;4988;4989 | chr2:178777201;178777200;178777199 | chr2:179641928;179641927;179641926 |
| N2A | 1588 | 4987;4988;4989 | chr2:178777201;178777200;178777199 | chr2:179641928;179641927;179641926 |
| N2B | 1542 | 4849;4850;4851 | chr2:178777201;178777200;178777199 | chr2:179641928;179641927;179641926 |
| Novex-1 | 1542 | 4849;4850;4851 | chr2:178777201;178777200;178777199 | chr2:179641928;179641927;179641926 |
| Novex-2 | 1542 | 4849;4850;4851 | chr2:178777201;178777200;178777199 | chr2:179641928;179641927;179641926 |
| Novex-3 | 1588 | 4987;4988;4989 | chr2:178777201;178777200;178777199 | chr2:179641928;179641927;179641926 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs1561301529  |
None | 0.928 | N | 0.573 | 0.319 | 0.610589977033 | gnomAD-4.0.0 | 1.59062E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.02151E-05 |
| V/I | rs1375582195 |
None | 0.039 | N | 0.308 | 0.121 | 0.470318359215 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| V/I | rs1375582195 |
None | 0.039 | N | 0.308 | 0.121 | 0.470318359215 | gnomAD-4.0.0 | 3.09789E-06 | None | None | None | None | N | None | 2.66937E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 8.47471E-07 | 2.19553E-05 | 0 |
| V/L | rs1375582195 |
-0.272 | 0.476 | D | 0.494 | 0.223 | 0.47185959272 | gnomAD-2.1.1 | 3.18E-05 | None | None | None | None | N | None | 1.14811E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/L | rs1375582195 |
-0.272 | 0.476 | D | 0.494 | 0.223 | 0.47185959272 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/L | rs1375582195 |
-0.272 | 0.476 | D | 0.494 | 0.223 | 0.47185959272 | gnomAD-4.0.0 | 6.56953E-06 | None | None | None | None | N | None | 2.41243E-05 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.8783 | likely_pathogenic | 0.8449 | pathogenic | -1.162 | Destabilizing | 0.928 | D | 0.573 | neutral | N | 0.502228287 | None | None | N |
| V/C | 0.9683 | likely_pathogenic | 0.9528 | pathogenic | -0.852 | Destabilizing | 0.999 | D | 0.773 | deleterious | None | None | None | None | N |
| V/D | 0.9978 | likely_pathogenic | 0.9968 | pathogenic | -1.003 | Destabilizing | 0.997 | D | 0.807 | deleterious | None | None | None | None | N |
| V/E | 0.9922 | likely_pathogenic | 0.9897 | pathogenic | -0.97 | Destabilizing | 0.996 | D | 0.756 | deleterious | N | 0.499725235 | None | None | N |
| V/F | 0.8522 | likely_pathogenic | 0.8209 | pathogenic | -0.769 | Destabilizing | 0.983 | D | 0.788 | deleterious | None | None | None | None | N |
| V/G | 0.962 | likely_pathogenic | 0.9457 | pathogenic | -1.486 | Destabilizing | 0.989 | D | 0.763 | deleterious | D | 0.63113572 | None | None | N |
| V/H | 0.9942 | likely_pathogenic | 0.9914 | pathogenic | -0.884 | Destabilizing | 0.999 | D | 0.813 | deleterious | None | None | None | None | N |
| V/I | 0.1953 | likely_benign | 0.1763 | benign | -0.369 | Destabilizing | 0.039 | N | 0.308 | neutral | N | 0.511086878 | None | None | N |
| V/K | 0.9916 | likely_pathogenic | 0.9876 | pathogenic | -1.049 | Destabilizing | 0.992 | D | 0.756 | deleterious | None | None | None | None | N |
| V/L | 0.8068 | likely_pathogenic | 0.764 | pathogenic | -0.369 | Destabilizing | 0.476 | N | 0.494 | neutral | D | 0.536608686 | None | None | N |
| V/M | 0.8415 | likely_pathogenic | 0.7956 | pathogenic | -0.407 | Destabilizing | 0.983 | D | 0.755 | deleterious | None | None | None | None | N |
| V/N | 0.9883 | likely_pathogenic | 0.9819 | pathogenic | -0.997 | Destabilizing | 0.997 | D | 0.821 | deleterious | None | None | None | None | N |
| V/P | 0.9975 | likely_pathogenic | 0.9958 | pathogenic | -0.598 | Destabilizing | 0.997 | D | 0.787 | deleterious | None | None | None | None | N |
| V/Q | 0.9821 | likely_pathogenic | 0.975 | pathogenic | -1.082 | Destabilizing | 0.997 | D | 0.799 | deleterious | None | None | None | None | N |
| V/R | 0.9737 | likely_pathogenic | 0.9648 | pathogenic | -0.583 | Destabilizing | 0.997 | D | 0.819 | deleterious | None | None | None | None | N |
| V/S | 0.9412 | likely_pathogenic | 0.9256 | pathogenic | -1.498 | Destabilizing | 0.992 | D | 0.752 | deleterious | None | None | None | None | N |
| V/T | 0.8855 | likely_pathogenic | 0.8488 | pathogenic | -1.342 | Destabilizing | 0.944 | D | 0.656 | neutral | None | None | None | None | N |
| V/W | 0.9977 | likely_pathogenic | 0.9962 | pathogenic | -0.994 | Destabilizing | 0.999 | D | 0.804 | deleterious | None | None | None | None | N |
| V/Y | 0.9839 | likely_pathogenic | 0.9767 | pathogenic | -0.664 | Destabilizing | 0.992 | D | 0.799 | 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.