Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17054 | 51385;51386;51387 | chr2:178610366;178610365;178610364 | chr2:179475093;179475092;179475091 |
| N2AB | 15413 | 46462;46463;46464 | chr2:178610366;178610365;178610364 | chr2:179475093;179475092;179475091 |
| N2A | 14486 | 43681;43682;43683 | chr2:178610366;178610365;178610364 | chr2:179475093;179475092;179475091 |
| N2B | 7989 | 24190;24191;24192 | chr2:178610366;178610365;178610364 | chr2:179475093;179475092;179475091 |
| Novex-1 | 8114 | 24565;24566;24567 | chr2:178610366;178610365;178610364 | chr2:179475093;179475092;179475091 |
| Novex-2 | 8181 | 24766;24767;24768 | chr2:178610366;178610365;178610364 | chr2:179475093;179475092;179475091 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/N | None | None | 0.859 | D | 0.833 | 0.534 | 0.814444702628 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| I/T | rs2056020027  |
None | 0.22 | D | 0.792 | 0.417 | 0.608471955132 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.75482E-04 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs1277276562 |
-1.201 | 0.025 | N | 0.517 | 0.097 | 0.495573750707 | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 8.9E-06 | 0 |
| I/V | rs1277276562 |
-1.201 | 0.025 | N | 0.517 | 0.097 | 0.495573750707 | gnomAD-4.0.0 | 3.18787E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.8632E-06 | 1.43382E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.8326 | likely_pathogenic | 0.8738 | pathogenic | -2.374 | Highly Destabilizing | 0.272 | N | 0.694 | prob.neutral | None | None | None | None | N |
| I/C | 0.8922 | likely_pathogenic | 0.9241 | pathogenic | -1.701 | Destabilizing | 0.968 | D | 0.737 | prob.delet. | None | None | None | None | N |
| I/D | 0.9929 | likely_pathogenic | 0.9957 | pathogenic | -2.336 | Highly Destabilizing | 0.89 | D | 0.839 | deleterious | None | None | None | None | N |
| I/E | 0.9839 | likely_pathogenic | 0.9897 | pathogenic | -2.147 | Highly Destabilizing | 0.726 | D | 0.831 | deleterious | None | None | None | None | N |
| I/F | 0.3286 | likely_benign | 0.3996 | ambiguous | -1.38 | Destabilizing | 0.331 | N | 0.739 | prob.delet. | N | 0.472535976 | None | None | N |
| I/G | 0.9639 | likely_pathogenic | 0.9778 | pathogenic | -2.896 | Highly Destabilizing | 0.726 | D | 0.831 | deleterious | None | None | None | None | N |
| I/H | 0.9742 | likely_pathogenic | 0.9829 | pathogenic | -2.289 | Highly Destabilizing | 0.968 | D | 0.824 | deleterious | None | None | None | None | N |
| I/K | 0.9653 | likely_pathogenic | 0.9771 | pathogenic | -1.835 | Destabilizing | 0.726 | D | 0.831 | deleterious | None | None | None | None | N |
| I/L | 0.0935 | likely_benign | 0.13 | benign | -0.892 | Destabilizing | None | N | 0.267 | neutral | N | 0.404568323 | None | None | N |
| I/M | 0.1501 | likely_benign | 0.1841 | benign | -0.853 | Destabilizing | 0.331 | N | 0.711 | prob.delet. | N | 0.469723882 | None | None | N |
| I/N | 0.9266 | likely_pathogenic | 0.951 | pathogenic | -2.032 | Highly Destabilizing | 0.859 | D | 0.833 | deleterious | D | 0.61300621 | None | None | N |
| I/P | 0.921 | likely_pathogenic | 0.9355 | pathogenic | -1.363 | Destabilizing | 0.89 | D | 0.832 | deleterious | None | None | None | None | N |
| I/Q | 0.9657 | likely_pathogenic | 0.9769 | pathogenic | -1.942 | Destabilizing | 0.89 | D | 0.841 | deleterious | None | None | None | None | N |
| I/R | 0.9567 | likely_pathogenic | 0.9697 | pathogenic | -1.519 | Destabilizing | 0.726 | D | 0.835 | deleterious | None | None | None | None | N |
| I/S | 0.912 | likely_pathogenic | 0.9367 | pathogenic | -2.761 | Highly Destabilizing | 0.667 | D | 0.793 | deleterious | D | 0.571040494 | None | None | N |
| I/T | 0.8485 | likely_pathogenic | 0.8782 | pathogenic | -2.427 | Highly Destabilizing | 0.22 | N | 0.792 | deleterious | D | 0.546297588 | None | None | N |
| I/V | 0.135 | likely_benign | 0.1394 | benign | -1.363 | Destabilizing | 0.025 | N | 0.517 | neutral | N | 0.435047468 | None | None | N |
| I/W | 0.9505 | likely_pathogenic | 0.9679 | pathogenic | -1.703 | Destabilizing | 0.968 | D | 0.818 | deleterious | None | None | None | None | N |
| I/Y | 0.8687 | likely_pathogenic | 0.9213 | pathogenic | -1.416 | Destabilizing | 0.726 | D | 0.777 | 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.