Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14081 | 42466;42467;42468 | chr2:178634540;178634539;178634538 | chr2:179499267;179499266;179499265 |
| N2AB | 12440 | 37543;37544;37545 | chr2:178634540;178634539;178634538 | chr2:179499267;179499266;179499265 |
| N2A | 11513 | 34762;34763;34764 | chr2:178634540;178634539;178634538 | chr2:179499267;179499266;179499265 |
| N2B | 5016 | 15271;15272;15273 | chr2:178634540;178634539;178634538 | chr2:179499267;179499266;179499265 |
| Novex-1 | 5141 | 15646;15647;15648 | chr2:178634540;178634539;178634538 | chr2:179499267;179499266;179499265 |
| Novex-2 | 5208 | 15847;15848;15849 | chr2:178634540;178634539;178634538 | chr2:179499267;179499266;179499265 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/T | rs1174918107  |
None | 1.0 | N | 0.775 | 0.457 | 0.444605663662 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/T | rs1174918107 |
None | 1.0 | N | 0.775 | 0.457 | 0.444605663662 | gnomAD-4.0.0 | 2.56387E-06 | None | None | None | None | N | None | 1.69337E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.39446E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.7889 | likely_pathogenic | 0.7669 | pathogenic | -0.694 | Destabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | N |
| A/D | 0.6884 | likely_pathogenic | 0.7182 | pathogenic | -1.299 | Destabilizing | 1.0 | D | 0.772 | deleterious | None | None | None | None | N |
| A/E | 0.6468 | likely_pathogenic | 0.659 | pathogenic | -1.337 | Destabilizing | 1.0 | D | 0.8 | deleterious | D | 0.675194433 | None | None | N |
| A/F | 0.8254 | likely_pathogenic | 0.8075 | pathogenic | -0.96 | Destabilizing | 1.0 | D | 0.762 | deleterious | None | None | None | None | N |
| A/G | 0.2459 | likely_benign | 0.2647 | benign | -1.006 | Destabilizing | 1.0 | D | 0.595 | neutral | D | 0.555795603 | None | None | N |
| A/H | 0.8693 | likely_pathogenic | 0.8645 | pathogenic | -1.174 | Destabilizing | 1.0 | D | 0.684 | prob.neutral | None | None | None | None | N |
| A/I | 0.7086 | likely_pathogenic | 0.6633 | pathogenic | -0.324 | Destabilizing | 1.0 | D | 0.788 | deleterious | None | None | None | None | N |
| A/K | 0.8425 | likely_pathogenic | 0.8277 | pathogenic | -1.206 | Destabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | N |
| A/L | 0.6674 | likely_pathogenic | 0.6106 | pathogenic | -0.324 | Destabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | N |
| A/M | 0.6161 | likely_pathogenic | 0.5911 | pathogenic | -0.327 | Destabilizing | 1.0 | D | 0.71 | prob.delet. | None | None | None | None | N |
| A/N | 0.6359 | likely_pathogenic | 0.6232 | pathogenic | -0.847 | Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | N |
| A/P | 0.9571 | likely_pathogenic | 0.9285 | pathogenic | -0.438 | Destabilizing | 1.0 | D | 0.781 | deleterious | N | 0.462698673 | None | None | N |
| A/Q | 0.6917 | likely_pathogenic | 0.6774 | pathogenic | -1.018 | Destabilizing | 1.0 | D | 0.776 | deleterious | None | None | None | None | N |
| A/R | 0.7888 | likely_pathogenic | 0.7895 | pathogenic | -0.818 | Destabilizing | 1.0 | D | 0.785 | deleterious | None | None | None | None | N |
| A/S | 0.1647 | likely_benign | 0.1731 | benign | -1.077 | Destabilizing | 1.0 | D | 0.625 | neutral | N | 0.510265871 | None | None | N |
| A/T | 0.2081 | likely_benign | 0.205 | benign | -1.028 | Destabilizing | 1.0 | D | 0.775 | deleterious | N | 0.499164703 | None | None | N |
| A/V | 0.3541 | ambiguous | 0.3267 | benign | -0.438 | Destabilizing | 1.0 | D | 0.712 | prob.delet. | N | 0.500876099 | None | None | N |
| A/W | 0.968 | likely_pathogenic | 0.964 | pathogenic | -1.295 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | N |
| A/Y | 0.888 | likely_pathogenic | 0.8794 | pathogenic | -0.896 | Destabilizing | 1.0 | D | 0.754 | 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.