Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15761 | 47506;47507;47508 | chr2:178618070;178618069;178618068 | chr2:179482797;179482796;179482795 |
| N2AB | 14120 | 42583;42584;42585 | chr2:178618070;178618069;178618068 | chr2:179482797;179482796;179482795 |
| N2A | 13193 | 39802;39803;39804 | chr2:178618070;178618069;178618068 | chr2:179482797;179482796;179482795 |
| N2B | 6696 | 20311;20312;20313 | chr2:178618070;178618069;178618068 | chr2:179482797;179482796;179482795 |
| Novex-1 | 6821 | 20686;20687;20688 | chr2:178618070;178618069;178618068 | chr2:179482797;179482796;179482795 |
| Novex-2 | 6888 | 20887;20888;20889 | chr2:178618070;178618069;178618068 | chr2:179482797;179482796;179482795 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | None | None | 0.961 | D | 0.788 | 0.464 | 0.669175797544 | gnomAD-4.0.0 | 1.5949E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86357E-06 | 0 | 0 |
| P/S | rs766763223  |
-1.568 | 0.925 | D | 0.715 | 0.386 | None | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | I | None | 6.48E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| P/S | rs766763223 |
-1.568 | 0.925 | D | 0.715 | 0.386 | None | gnomAD-3.1.2 | 6.59E-06 | None | None | None | None | I | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/S | rs766763223 |
-1.568 | 0.925 | D | 0.715 | 0.386 | None | gnomAD-4.0.0 | 6.58579E-06 | None | None | None | None | I | None | 2.41639E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0926 | likely_benign | 0.0843 | benign | -1.808 | Destabilizing | 0.044 | N | 0.423 | neutral | N | 0.46515017 | None | None | I |
| P/C | 0.6225 | likely_pathogenic | 0.5798 | pathogenic | -1.285 | Destabilizing | 1.0 | D | 0.82 | deleterious | None | None | None | None | I |
| P/D | 0.7925 | likely_pathogenic | 0.7893 | pathogenic | -2.234 | Highly Destabilizing | 0.996 | D | 0.719 | prob.delet. | None | None | None | None | I |
| P/E | 0.4784 | ambiguous | 0.4808 | ambiguous | -2.211 | Highly Destabilizing | 0.985 | D | 0.708 | prob.delet. | None | None | None | None | I |
| P/F | 0.6622 | likely_pathogenic | 0.634 | pathogenic | -1.353 | Destabilizing | 0.999 | D | 0.835 | deleterious | None | None | None | None | I |
| P/G | 0.4874 | ambiguous | 0.4576 | ambiguous | -2.144 | Highly Destabilizing | 0.942 | D | 0.757 | deleterious | None | None | None | None | I |
| P/H | 0.3961 | ambiguous | 0.3879 | ambiguous | -1.676 | Destabilizing | 1.0 | D | 0.793 | deleterious | D | 0.66343 | None | None | I |
| P/I | 0.5122 | ambiguous | 0.4689 | ambiguous | -0.954 | Destabilizing | 0.996 | D | 0.809 | deleterious | None | None | None | None | I |
| P/K | 0.5678 | likely_pathogenic | 0.5514 | ambiguous | -1.498 | Destabilizing | 0.97 | D | 0.707 | prob.neutral | None | None | None | None | I |
| P/L | 0.3246 | likely_benign | 0.297 | benign | -0.954 | Destabilizing | 0.961 | D | 0.788 | deleterious | D | 0.722508664 | None | None | I |
| P/M | 0.479 | ambiguous | 0.4453 | ambiguous | -0.778 | Destabilizing | 1.0 | D | 0.798 | deleterious | None | None | None | None | I |
| P/N | 0.6026 | likely_pathogenic | 0.585 | pathogenic | -1.377 | Destabilizing | 0.999 | D | 0.798 | deleterious | None | None | None | None | I |
| P/Q | 0.2709 | likely_benign | 0.2568 | benign | -1.565 | Destabilizing | 0.999 | D | 0.72 | prob.delet. | None | None | None | None | I |
| P/R | 0.4021 | ambiguous | 0.3814 | ambiguous | -0.955 | Destabilizing | 0.994 | D | 0.793 | deleterious | D | 0.598591039 | None | None | I |
| P/S | 0.1772 | likely_benign | 0.1704 | benign | -1.848 | Destabilizing | 0.925 | D | 0.715 | prob.delet. | D | 0.524737777 | None | None | I |
| P/T | 0.2471 | likely_benign | 0.2159 | benign | -1.727 | Destabilizing | 0.961 | D | 0.697 | prob.neutral | D | 0.646062368 | None | None | I |
| P/V | 0.3686 | ambiguous | 0.3316 | benign | -1.207 | Destabilizing | 0.97 | D | 0.749 | deleterious | None | None | None | None | I |
| P/W | 0.8611 | likely_pathogenic | 0.8499 | pathogenic | -1.596 | Destabilizing | 1.0 | D | 0.819 | deleterious | None | None | None | None | I |
| P/Y | 0.6596 | likely_pathogenic | 0.6422 | pathogenic | -1.327 | Destabilizing | 0.999 | D | 0.835 | deleterious | None | None | None | None | I |
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.