Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31236 | 93931;93932;93933 | chr2:178547920;178547919;178547918 | chr2:179412647;179412646;179412645 |
| N2AB | 29595 | 89008;89009;89010 | chr2:178547920;178547919;178547918 | chr2:179412647;179412646;179412645 |
| N2A | 28668 | 86227;86228;86229 | chr2:178547920;178547919;178547918 | chr2:179412647;179412646;179412645 |
| N2B | 22171 | 66736;66737;66738 | chr2:178547920;178547919;178547918 | chr2:179412647;179412646;179412645 |
| Novex-1 | 22296 | 67111;67112;67113 | chr2:178547920;178547919;178547918 | chr2:179412647;179412646;179412645 |
| Novex-2 | 22363 | 67312;67313;67314 | chr2:178547920;178547919;178547918 | chr2:179412647;179412646;179412645 |
| 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 | rs560835240  |
-0.026 | 0.092 | N | 0.357 | 0.134 | 0.0884992946249 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 9.95E-05 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/E | rs560835240 |
-0.026 | 0.092 | N | 0.357 | 0.134 | 0.0884992946249 | gnomAD-4.0.0 | 6.84202E-07 | None | None | None | None | I | None | 0 | 0 | None | 3.82731E-05 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/N | rs1697878797 |
None | 0.978 | N | 0.677 | 0.33 | 0.430923071578 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/N | rs1697878797 |
None | 0.978 | N | 0.677 | 0.33 | 0.430923071578 | gnomAD-4.0.0 | 6.57523E-06 | None | None | None | None | I | None | 2.41429E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.2925 | likely_benign | 0.328 | benign | -0.426 | Destabilizing | 0.957 | D | 0.709 | prob.delet. | D | 0.524322631 | None | None | I |
| D/C | 0.8047 | likely_pathogenic | 0.8255 | pathogenic | -0.094 | Destabilizing | 0.999 | D | 0.755 | deleterious | None | None | None | None | I |
| D/E | 0.2573 | likely_benign | 0.2858 | benign | -0.666 | Destabilizing | 0.092 | N | 0.357 | neutral | N | 0.479222272 | None | None | I |
| D/F | 0.8031 | likely_pathogenic | 0.8374 | pathogenic | -0.194 | Destabilizing | 0.999 | D | 0.767 | deleterious | None | None | None | None | I |
| D/G | 0.4621 | ambiguous | 0.5138 | ambiguous | -0.742 | Destabilizing | 0.928 | D | 0.713 | prob.delet. | N | 0.490176235 | None | None | I |
| D/H | 0.4284 | ambiguous | 0.4504 | ambiguous | -0.474 | Destabilizing | 0.997 | D | 0.766 | deleterious | N | 0.518802168 | None | None | I |
| D/I | 0.5104 | ambiguous | 0.5596 | ambiguous | 0.39 | Stabilizing | 0.992 | D | 0.789 | deleterious | None | None | None | None | I |
| D/K | 0.6711 | likely_pathogenic | 0.6913 | pathogenic | -0.13 | Destabilizing | 0.968 | D | 0.748 | deleterious | None | None | None | None | I |
| D/L | 0.5669 | likely_pathogenic | 0.6129 | pathogenic | 0.39 | Stabilizing | 0.983 | D | 0.769 | deleterious | None | None | None | None | I |
| D/M | 0.7578 | likely_pathogenic | 0.7951 | pathogenic | 0.744 | Stabilizing | 0.999 | D | 0.759 | deleterious | None | None | None | None | I |
| D/N | 0.1651 | likely_benign | 0.1634 | benign | -0.552 | Destabilizing | 0.978 | D | 0.677 | prob.neutral | N | 0.489151264 | None | None | I |
| D/P | 0.8549 | likely_pathogenic | 0.877 | pathogenic | 0.143 | Stabilizing | 0.992 | D | 0.793 | deleterious | None | None | None | None | I |
| D/Q | 0.5432 | ambiguous | 0.5855 | pathogenic | -0.443 | Destabilizing | 0.968 | D | 0.733 | prob.delet. | None | None | None | None | I |
| D/R | 0.6606 | likely_pathogenic | 0.676 | pathogenic | -0.021 | Destabilizing | 0.983 | D | 0.76 | deleterious | None | None | None | None | I |
| D/S | 0.1881 | likely_benign | 0.1988 | benign | -0.733 | Destabilizing | 0.895 | D | 0.62 | neutral | None | None | None | None | I |
| D/T | 0.3158 | likely_benign | 0.3501 | ambiguous | -0.478 | Destabilizing | 0.983 | D | 0.785 | deleterious | None | None | None | None | I |
| D/V | 0.3094 | likely_benign | 0.3467 | ambiguous | 0.143 | Stabilizing | 0.978 | D | 0.773 | deleterious | D | 0.529576522 | None | None | I |
| D/W | 0.9578 | likely_pathogenic | 0.9645 | pathogenic | -0.049 | Destabilizing | 0.999 | D | 0.755 | deleterious | None | None | None | None | I |
| D/Y | 0.4608 | ambiguous | 0.4766 | ambiguous | 0.044 | Stabilizing | 0.999 | D | 0.767 | deleterious | N | 0.521938473 | 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.