Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35482 | 106669;106670;106671 | chr2:178530047;178530046;178530045 | chr2:179394774;179394773;179394772 |
| N2AB | 33841 | 101746;101747;101748 | chr2:178530047;178530046;178530045 | chr2:179394774;179394773;179394772 |
| N2A | 32914 | 98965;98966;98967 | chr2:178530047;178530046;178530045 | chr2:179394774;179394773;179394772 |
| N2B | 26417 | 79474;79475;79476 | chr2:178530047;178530046;178530045 | chr2:179394774;179394773;179394772 |
| Novex-1 | 26542 | 79849;79850;79851 | chr2:178530047;178530046;178530045 | chr2:179394774;179394773;179394772 |
| Novex-2 | 26609 | 80050;80051;80052 | chr2:178530047;178530046;178530045 | chr2:179394774;179394773;179394772 |
| 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/A | rs1423470146  |
-0.134 | 0.114 | N | 0.23 | 0.208 | 0.173771789658 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.33E-05 | None | 0 | 0 | 0 |
| T/A | rs1423470146 |
-0.134 | 0.114 | N | 0.23 | 0.208 | 0.173771789658 | gnomAD-4.0.0 | 1.59654E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.44932E-05 | 0 |
| T/S | rs1423470146 |
None | 0.664 | N | 0.513 | 0.148 | 0.256793551483 | gnomAD-4.0.0 | 3.19307E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.72452E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1216 | likely_benign | 0.1109 | benign | -0.629 | Destabilizing | 0.114 | N | 0.23 | neutral | N | 0.399873267 | None | None | N |
| T/C | 0.7157 | likely_pathogenic | 0.6896 | pathogenic | -1.375 | Destabilizing | 0.999 | D | 0.605 | neutral | None | None | None | None | N |
| T/D | 0.7063 | likely_pathogenic | 0.742 | pathogenic | -2.588 | Highly Destabilizing | 0.989 | D | 0.628 | neutral | None | None | None | None | N |
| T/E | 0.5882 | likely_pathogenic | 0.6352 | pathogenic | -2.464 | Highly Destabilizing | 0.963 | D | 0.595 | neutral | None | None | None | None | N |
| T/F | 0.6011 | likely_pathogenic | 0.5866 | pathogenic | -0.938 | Destabilizing | 0.989 | D | 0.634 | neutral | None | None | None | None | N |
| T/G | 0.3925 | ambiguous | 0.4227 | ambiguous | -0.885 | Destabilizing | 0.864 | D | 0.553 | neutral | None | None | None | None | N |
| T/H | 0.6972 | likely_pathogenic | 0.7126 | pathogenic | -1.194 | Destabilizing | 0.999 | D | 0.605 | neutral | None | None | None | None | N |
| T/I | 0.2982 | likely_benign | 0.2607 | benign | -0.016 | Destabilizing | 0.827 | D | 0.583 | neutral | N | 0.407743389 | None | None | N |
| T/K | 0.4881 | ambiguous | 0.5354 | ambiguous | -0.673 | Destabilizing | 0.927 | D | 0.587 | neutral | None | None | None | None | N |
| T/L | 0.2125 | likely_benign | 0.1898 | benign | -0.016 | Destabilizing | 0.724 | D | 0.509 | neutral | None | None | None | None | N |
| T/M | 0.1285 | likely_benign | 0.1241 | benign | -0.095 | Destabilizing | 0.533 | D | 0.483 | neutral | None | None | None | None | N |
| T/N | 0.2653 | likely_benign | 0.2959 | benign | -1.502 | Destabilizing | 0.995 | D | 0.591 | neutral | D | 0.522322475 | None | None | N |
| T/P | 0.285 | likely_benign | 0.2371 | benign | -0.192 | Destabilizing | 0.986 | D | 0.628 | neutral | N | 0.46737327 | None | None | N |
| T/Q | 0.5479 | ambiguous | 0.5896 | pathogenic | -1.555 | Destabilizing | 0.989 | D | 0.633 | neutral | None | None | None | None | N |
| T/R | 0.4346 | ambiguous | 0.4766 | ambiguous | -0.589 | Destabilizing | 0.989 | D | 0.629 | neutral | None | None | None | None | N |
| T/S | 0.206 | likely_benign | 0.2166 | benign | -1.39 | Destabilizing | 0.664 | D | 0.513 | neutral | N | 0.471797655 | None | None | N |
| T/V | 0.2432 | likely_benign | 0.214 | benign | -0.192 | Destabilizing | 0.724 | D | 0.505 | neutral | None | None | None | None | N |
| T/W | 0.866 | likely_pathogenic | 0.8681 | pathogenic | -1.22 | Destabilizing | 0.999 | D | 0.601 | neutral | None | None | None | None | N |
| T/Y | 0.6761 | likely_pathogenic | 0.6675 | pathogenic | -0.703 | Destabilizing | 0.996 | D | 0.611 | neutral | 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.