Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32263 | 97012;97013;97014 | chr2:178543186;178543185;178543184 | chr2:179407913;179407912;179407911 |
| N2AB | 30622 | 92089;92090;92091 | chr2:178543186;178543185;178543184 | chr2:179407913;179407912;179407911 |
| N2A | 29695 | 89308;89309;89310 | chr2:178543186;178543185;178543184 | chr2:179407913;179407912;179407911 |
| N2B | 23198 | 69817;69818;69819 | chr2:178543186;178543185;178543184 | chr2:179407913;179407912;179407911 |
| Novex-1 | 23323 | 70192;70193;70194 | chr2:178543186;178543185;178543184 | chr2:179407913;179407912;179407911 |
| Novex-2 | 23390 | 70393;70394;70395 | chr2:178543186;178543185;178543184 | chr2:179407913;179407912;179407911 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs762871001  |
0.205 | 0.612 | N | 0.276 | 0.382 | 0.38225645794 | gnomAD-2.1.1 | 8.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.77E-05 | 0 |
| T/I | rs762871001 |
0.205 | 0.612 | N | 0.276 | 0.382 | 0.38225645794 | gnomAD-4.0.0 | 1.36849E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99515E-07 | 1.15934E-05 | 0 |
| T/N | None | None | 0.996 | N | 0.623 | 0.387 | 0.404034981753 | gnomAD-4.0.0 | 6.84244E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99515E-07 | 0 | 0 |
| T/S | rs762871001 |
-1.021 | 0.956 | N | 0.397 | 0.424 | 0.245660935333 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| T/S | rs762871001 |
-1.021 | 0.956 | N | 0.397 | 0.424 | 0.245660935333 | gnomAD-4.0.0 | 6.84244E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15934E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1066 | likely_benign | 0.094 | benign | -0.664 | Destabilizing | 0.878 | D | 0.437 | neutral | N | 0.480681764 | None | None | N |
| T/C | 0.4079 | ambiguous | 0.3587 | ambiguous | -0.345 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | N |
| T/D | 0.5848 | likely_pathogenic | 0.559 | ambiguous | -0.472 | Destabilizing | 0.997 | D | 0.713 | prob.delet. | None | None | None | None | N |
| T/E | 0.3768 | ambiguous | 0.3529 | ambiguous | -0.492 | Destabilizing | 0.999 | D | 0.713 | prob.delet. | None | None | None | None | N |
| T/F | 0.4053 | ambiguous | 0.3403 | ambiguous | -0.809 | Destabilizing | 0.999 | D | 0.773 | deleterious | None | None | None | None | N |
| T/G | 0.3677 | ambiguous | 0.3413 | ambiguous | -0.908 | Destabilizing | 1.0 | D | 0.667 | neutral | None | None | None | None | N |
| T/H | 0.3287 | likely_benign | 0.2896 | benign | -1.276 | Destabilizing | 1.0 | D | 0.774 | deleterious | None | None | None | None | N |
| T/I | 0.1702 | likely_benign | 0.1456 | benign | -0.112 | Destabilizing | 0.612 | D | 0.276 | neutral | N | 0.477870607 | None | None | N |
| T/K | 0.2205 | likely_benign | 0.2064 | benign | -0.808 | Destabilizing | 0.999 | D | 0.715 | prob.delet. | None | None | None | None | N |
| T/L | 0.1546 | likely_benign | 0.129 | benign | -0.112 | Destabilizing | 0.971 | D | 0.505 | neutral | None | None | None | None | N |
| T/M | 0.1185 | likely_benign | 0.101 | benign | 0.243 | Stabilizing | 0.999 | D | 0.735 | prob.delet. | None | None | None | None | N |
| T/N | 0.2304 | likely_benign | 0.2062 | benign | -0.703 | Destabilizing | 0.996 | D | 0.623 | neutral | N | 0.516292219 | None | None | N |
| T/P | 0.2887 | likely_benign | 0.2586 | benign | -0.263 | Destabilizing | 0.996 | D | 0.741 | deleterious | N | 0.481695722 | None | None | N |
| T/Q | 0.2512 | likely_benign | 0.232 | benign | -0.893 | Destabilizing | 0.999 | D | 0.757 | deleterious | None | None | None | None | N |
| T/R | 0.1747 | likely_benign | 0.1602 | benign | -0.535 | Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | N |
| T/S | 0.1535 | likely_benign | 0.1403 | benign | -0.888 | Destabilizing | 0.956 | D | 0.397 | neutral | N | 0.486428982 | None | None | N |
| T/V | 0.1174 | likely_benign | 0.1049 | benign | -0.263 | Destabilizing | 0.909 | D | 0.443 | neutral | None | None | None | None | N |
| T/W | 0.7578 | likely_pathogenic | 0.7074 | pathogenic | -0.79 | Destabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | N |
| T/Y | 0.4566 | ambiguous | 0.4017 | ambiguous | -0.555 | Destabilizing | 1.0 | D | 0.785 | 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.