Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 7846 | 23761;23762;23763 | chr2:178720106;178720105;178720104 | chr2:179584833;179584832;179584831 |
| N2AB | 7529 | 22810;22811;22812 | chr2:178720106;178720105;178720104 | chr2:179584833;179584832;179584831 |
| N2A | 6602 | 20029;20030;20031 | chr2:178720106;178720105;178720104 | chr2:179584833;179584832;179584831 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/L | rs149523263  |
-1.116 | 0.885 | D | 0.639 | 0.329 | 0.608069465739 | gnomAD-2.1.1 | 3.42798E-03 | None | None | None | None | N | None | 1.24049E-04 | 7.63661E-04 | None | 1.06404E-03 | 0 | None | 2.18642E-02 | None | 4E-05 | 1.77455E-03 | 3.08989E-03 |
| F/L | rs149523263 |
-1.116 | 0.885 | D | 0.639 | 0.329 | 0.608069465739 | gnomAD-3.1.2 | 1.74839E-03 | None | None | None | None | N | None | 1.6896E-04 | 1.70202E-03 | 0 | 8.64055E-04 | 0 | None | 0 | 0 | 1.64686E-03 | 2.38194E-02 | 1.43403E-03 |
| F/L | rs149523263 |
-1.116 | 0.885 | D | 0.639 | 0.329 | 0.608069465739 | 1000 genomes | 5.99042E-03 | None | None | None | None | N | None | 0 | 1.4E-03 | None | None | 0 | 2E-03 | None | None | None | 2.76E-02 | None |
| F/L | rs149523263 |
-1.116 | 0.885 | D | 0.639 | 0.329 | 0.608069465739 | gnomAD-4.0.0 | 1.36846E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79902E-06 | 0 | 0 |
| F/Y | rs397517504 |
None | 0.02 | N | 0.325 | 0.202 | 0.315609569513 | gnomAD-4.0.0 | 1.59144E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85881E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.9275 | likely_pathogenic | 0.9138 | pathogenic | -2.144 | Highly Destabilizing | 0.953 | D | 0.745 | deleterious | None | None | None | None | N |
| F/C | 0.7053 | likely_pathogenic | 0.6442 | pathogenic | -1.191 | Destabilizing | 0.999 | D | 0.813 | deleterious | N | 0.51064712 | None | None | N |
| F/D | 0.9749 | likely_pathogenic | 0.9663 | pathogenic | -0.729 | Destabilizing | 0.998 | D | 0.83 | deleterious | None | None | None | None | N |
| F/E | 0.978 | likely_pathogenic | 0.9745 | pathogenic | -0.625 | Destabilizing | 0.993 | D | 0.824 | deleterious | None | None | None | None | N |
| F/G | 0.9676 | likely_pathogenic | 0.9581 | pathogenic | -2.497 | Highly Destabilizing | 0.993 | D | 0.798 | deleterious | None | None | None | None | N |
| F/H | 0.791 | likely_pathogenic | 0.7516 | pathogenic | -0.772 | Destabilizing | 0.986 | D | 0.787 | deleterious | None | None | None | None | N |
| F/I | 0.5368 | ambiguous | 0.4992 | ambiguous | -1.082 | Destabilizing | 0.982 | D | 0.728 | prob.delet. | N | 0.487262946 | None | None | N |
| F/K | 0.9798 | likely_pathogenic | 0.9766 | pathogenic | -1.175 | Destabilizing | 0.993 | D | 0.825 | deleterious | None | None | None | None | N |
| F/L | 0.9406 | likely_pathogenic | 0.9247 | pathogenic | -1.082 | Destabilizing | 0.885 | D | 0.639 | neutral | D | 0.525842783 | None | None | N |
| F/M | 0.7994 | likely_pathogenic | 0.7789 | pathogenic | -0.838 | Destabilizing | 0.999 | D | 0.754 | deleterious | None | None | None | None | N |
| F/N | 0.9051 | likely_pathogenic | 0.882 | pathogenic | -1.246 | Destabilizing | 0.998 | D | 0.839 | deleterious | None | None | None | None | N |
| F/P | 0.998 | likely_pathogenic | 0.9974 | pathogenic | -1.43 | Destabilizing | 0.998 | D | 0.827 | deleterious | None | None | None | None | N |
| F/Q | 0.9536 | likely_pathogenic | 0.9467 | pathogenic | -1.288 | Destabilizing | 0.998 | D | 0.833 | deleterious | None | None | None | None | N |
| F/R | 0.9436 | likely_pathogenic | 0.9366 | pathogenic | -0.573 | Destabilizing | 0.993 | D | 0.836 | deleterious | None | None | None | None | N |
| F/S | 0.8467 | likely_pathogenic | 0.8097 | pathogenic | -2.102 | Highly Destabilizing | 0.991 | D | 0.795 | deleterious | N | 0.482628137 | None | None | N |
| F/T | 0.8898 | likely_pathogenic | 0.8713 | pathogenic | -1.902 | Destabilizing | 0.993 | D | 0.809 | deleterious | None | None | None | None | N |
| F/V | 0.5029 | ambiguous | 0.4768 | ambiguous | -1.43 | Destabilizing | 0.939 | D | 0.701 | prob.neutral | D | 0.524282558 | None | None | N |
| F/W | 0.6537 | likely_pathogenic | 0.6149 | pathogenic | -0.193 | Destabilizing | 0.998 | D | 0.739 | prob.delet. | None | None | None | None | N |
| F/Y | 0.183 | likely_benign | 0.158 | benign | -0.42 | Destabilizing | 0.02 | N | 0.325 | neutral | N | 0.446939282 | 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.