Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31508 | 94747;94748;94749 | chr2:178547003;178546905;178546904 | chr2:179411730;179411632;179411631 |
| N2AB | 29867 | 89824;89825;89826 | chr2:178547003;178546905;178546904 | chr2:179411730;179411632;179411631 |
| N2A | 28940 | 87043;87044;87045 | chr2:178547003;178546905;178546904 | chr2:179411730;179411632;179411631 |
| N2B | 22443 | 67552;67553;67554 | chr2:178547003;178546905;178546904 | chr2:179411730;179411632;179411631 |
| Novex-1 | 22568 | 67927;67928;67929 | chr2:178547003;178546905;178546904 | chr2:179411730;179411632;179411631 |
| Novex-2 | 22635 | 68128;68129;68130 | chr2:178547003;178546905;178546904 | chr2:179411730;179411632;179411631 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | rs727505200  |
-0.351 | 1.0 | N | 0.659 | None | 0.365317461125 | gnomAD-2.1.1 | 1.57E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.54E-05 | 1.56348E-04 |
| D/E | rs727505200 |
-0.351 | 1.0 | N | 0.659 | None | 0.365317461125 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 5.88E-05 | 0 | 0 |
| D/E | rs727505200 |
-0.351 | 1.0 | N | 0.659 | None | 0.365317461125 | gnomAD-4.0.0 | 1.70964E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.32623E-05 | 0 | 0 |
| D/G | rs772571812 |
None | 1.0 | N | 0.834 | None | 0.303781844768 | gnomAD-4.0.0 | 1.68489E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.56133E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.4634 | ambiguous | 0.4311 | ambiguous | -0.638 | Destabilizing | 1.0 | D | 0.847 | deleterious | N | 0.508169498 | None | None | N |
| D/C | 0.9185 | likely_pathogenic | 0.9018 | pathogenic | -0.273 | Destabilizing | 1.0 | D | 0.866 | deleterious | None | None | None | None | N |
| D/E | 0.4589 | ambiguous | 0.4102 | ambiguous | -0.56 | Destabilizing | 1.0 | D | 0.659 | neutral | N | 0.485430434 | None | None | N |
| D/F | 0.9399 | likely_pathogenic | 0.9265 | pathogenic | -0.188 | Destabilizing | 1.0 | D | 0.881 | deleterious | None | None | None | None | N |
| D/G | 0.4518 | ambiguous | 0.4255 | ambiguous | -0.991 | Destabilizing | 1.0 | D | 0.834 | deleterious | N | 0.459080064 | None | None | N |
| D/H | 0.8194 | likely_pathogenic | 0.8083 | pathogenic | -0.506 | Destabilizing | 1.0 | D | 0.881 | deleterious | D | 0.531642577 | None | None | N |
| D/I | 0.9433 | likely_pathogenic | 0.9175 | pathogenic | 0.296 | Stabilizing | 1.0 | D | 0.877 | deleterious | None | None | None | None | N |
| D/K | 0.9261 | likely_pathogenic | 0.9183 | pathogenic | -0.362 | Destabilizing | 1.0 | D | 0.865 | deleterious | None | None | None | None | N |
| D/L | 0.8475 | likely_pathogenic | 0.8224 | pathogenic | 0.296 | Stabilizing | 1.0 | D | 0.885 | deleterious | None | None | None | None | N |
| D/M | 0.9338 | likely_pathogenic | 0.9124 | pathogenic | 0.694 | Stabilizing | 1.0 | D | 0.836 | deleterious | None | None | None | None | N |
| D/N | 0.4001 | ambiguous | 0.3867 | ambiguous | -0.793 | Destabilizing | 1.0 | D | 0.844 | deleterious | N | 0.503623594 | None | None | N |
| D/P | 0.9894 | likely_pathogenic | 0.9825 | pathogenic | 0.01 | Stabilizing | 1.0 | D | 0.885 | deleterious | None | None | None | None | N |
| D/Q | 0.8227 | likely_pathogenic | 0.8079 | pathogenic | -0.659 | Destabilizing | 1.0 | D | 0.854 | deleterious | None | None | None | None | N |
| D/R | 0.9278 | likely_pathogenic | 0.9191 | pathogenic | -0.207 | Destabilizing | 1.0 | D | 0.898 | deleterious | None | None | None | None | N |
| D/S | 0.3245 | likely_benign | 0.3135 | benign | -1.07 | Destabilizing | 1.0 | D | 0.819 | deleterious | None | None | None | None | N |
| D/T | 0.7584 | likely_pathogenic | 0.7103 | pathogenic | -0.778 | Destabilizing | 1.0 | D | 0.866 | deleterious | None | None | None | None | N |
| D/V | 0.8274 | likely_pathogenic | 0.7634 | pathogenic | 0.01 | Stabilizing | 1.0 | D | 0.885 | deleterious | N | 0.52104674 | None | None | N |
| D/W | 0.9897 | likely_pathogenic | 0.9882 | pathogenic | 0.027 | Stabilizing | 1.0 | D | 0.877 | deleterious | None | None | None | None | N |
| D/Y | 0.7363 | likely_pathogenic | 0.7162 | pathogenic | 0.065 | Stabilizing | 1.0 | D | 0.879 | deleterious | N | 0.502688996 | 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.