Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 13937 | 42034;42035;42036 | chr2:178635515;178635514;178635513 | chr2:179500242;179500241;179500240 |
| N2AB | 12296 | 37111;37112;37113 | chr2:178635515;178635514;178635513 | chr2:179500242;179500241;179500240 |
| N2A | 11369 | 34330;34331;34332 | chr2:178635515;178635514;178635513 | chr2:179500242;179500241;179500240 |
| N2B | 4872 | 14839;14840;14841 | chr2:178635515;178635514;178635513 | chr2:179500242;179500241;179500240 |
| Novex-1 | 4997 | 15214;15215;15216 | chr2:178635515;178635514;178635513 | chr2:179500242;179500241;179500240 |
| Novex-2 | 5064 | 15415;15416;15417 | chr2:178635515;178635514;178635513 | chr2:179500242;179500241;179500240 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/D | None | None | 0.963 | N | 0.771 | 0.256 | 0.566919426312 | gnomAD-4.0.0 | 6.90088E-07 | None | None | None | None | N | None | 0 | 2.33242E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/V | rs545806408  |
-0.426 | 0.016 | N | 0.418 | 0.072 | 0.327686398923 | gnomAD-2.1.1 | 4.2682E-04 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.32773E-03 | None | 0 | 1.99E-05 | 0 |
| A/V | rs545806408 |
-0.426 | 0.016 | N | 0.418 | 0.072 | 0.327686398923 | gnomAD-3.1.2 | 1.31581E-04 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 3.94518E-03 | 0 |
| A/V | rs545806408 |
-0.426 | 0.016 | N | 0.418 | 0.072 | 0.327686398923 | 1000 genomes | 1.39776E-03 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 7.2E-03 | None |
| A/V | rs545806408 |
-0.426 | 0.016 | N | 0.418 | 0.072 | 0.327686398923 | gnomAD-4.0.0 | 1.69248E-04 | None | None | None | None | N | None | 1.33504E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 5.11537E-06 | 2.77175E-03 | 2.58006E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.5163 | ambiguous | 0.6217 | pathogenic | -1.379 | Destabilizing | 0.005 | N | 0.368 | neutral | None | None | None | None | N |
| A/D | 0.9927 | likely_pathogenic | 0.9936 | pathogenic | -2.253 | Highly Destabilizing | 0.963 | D | 0.771 | deleterious | N | 0.51269937 | None | None | N |
| A/E | 0.9905 | likely_pathogenic | 0.9897 | pathogenic | -2.268 | Highly Destabilizing | 0.972 | D | 0.718 | prob.delet. | None | None | None | None | N |
| A/F | 0.9741 | likely_pathogenic | 0.9683 | pathogenic | -1.245 | Destabilizing | 0.919 | D | 0.76 | deleterious | None | None | None | None | N |
| A/G | 0.5751 | likely_pathogenic | 0.6516 | pathogenic | -1.262 | Destabilizing | 0.546 | D | 0.623 | neutral | N | 0.51269937 | None | None | N |
| A/H | 0.9939 | likely_pathogenic | 0.9941 | pathogenic | -1.379 | Destabilizing | 0.992 | D | 0.775 | deleterious | None | None | None | None | N |
| A/I | 0.6615 | likely_pathogenic | 0.6358 | pathogenic | -0.455 | Destabilizing | 0.444 | N | 0.687 | prob.delet. | None | None | None | None | N |
| A/K | 0.9976 | likely_pathogenic | 0.9973 | pathogenic | -1.314 | Destabilizing | 0.919 | D | 0.723 | deleterious | None | None | None | None | N |
| A/L | 0.6041 | likely_pathogenic | 0.5768 | pathogenic | -0.455 | Destabilizing | 0.248 | N | 0.649 | prob.neutral | None | None | None | None | N |
| A/M | 0.8342 | likely_pathogenic | 0.8306 | pathogenic | -0.404 | Destabilizing | 0.919 | D | 0.731 | deleterious | None | None | None | None | N |
| A/N | 0.9689 | likely_pathogenic | 0.9764 | pathogenic | -1.269 | Destabilizing | 0.972 | D | 0.759 | deleterious | None | None | None | None | N |
| A/P | 0.9191 | likely_pathogenic | 0.9172 | pathogenic | -0.602 | Destabilizing | 0.963 | D | 0.753 | deleterious | N | 0.510173927 | None | None | N |
| A/Q | 0.9844 | likely_pathogenic | 0.9849 | pathogenic | -1.477 | Destabilizing | 0.972 | D | 0.73 | deleterious | None | None | None | None | N |
| A/R | 0.9908 | likely_pathogenic | 0.9891 | pathogenic | -0.953 | Destabilizing | 0.972 | D | 0.755 | deleterious | None | None | None | None | N |
| A/S | 0.3942 | ambiguous | 0.451 | ambiguous | -1.537 | Destabilizing | 0.546 | D | 0.635 | neutral | N | 0.510173927 | None | None | N |
| A/T | 0.349 | ambiguous | 0.3743 | ambiguous | -1.471 | Destabilizing | 0.546 | D | 0.631 | neutral | N | 0.507100757 | None | None | N |
| A/V | 0.2796 | likely_benign | 0.2039 | benign | -0.602 | Destabilizing | 0.016 | N | 0.418 | neutral | N | 0.439281892 | None | None | N |
| A/W | 0.9987 | likely_pathogenic | 0.998 | pathogenic | -1.619 | Destabilizing | 0.992 | D | 0.798 | deleterious | None | None | None | None | N |
| A/Y | 0.9927 | likely_pathogenic | 0.991 | pathogenic | -1.206 | Destabilizing | 0.972 | D | 0.76 | 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.