Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17814 | 53665;53666;53667 | chr2:178607162;178607161;178607160 | chr2:179471889;179471888;179471887 |
| N2AB | 16173 | 48742;48743;48744 | chr2:178607162;178607161;178607160 | chr2:179471889;179471888;179471887 |
| N2A | 15246 | 45961;45962;45963 | chr2:178607162;178607161;178607160 | chr2:179471889;179471888;179471887 |
| N2B | 8749 | 26470;26471;26472 | chr2:178607162;178607161;178607160 | chr2:179471889;179471888;179471887 |
| Novex-1 | 8874 | 26845;26846;26847 | chr2:178607162;178607161;178607160 | chr2:179471889;179471888;179471887 |
| Novex-2 | 8941 | 27046;27047;27048 | chr2:178607162;178607161;178607160 | chr2:179471889;179471888;179471887 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/R | rs1332418723  |
-0.724 | 0.782 | D | 0.741 | 0.329 | 0.473538153929 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| P/R | rs1332418723 |
-0.724 | 0.782 | D | 0.741 | 0.329 | 0.473538153929 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| P/R | rs1332418723 |
-0.724 | 0.782 | D | 0.741 | 0.329 | 0.473538153929 | gnomAD-4.0.0 | 7.44046E-06 | None | None | None | None | N | None | 0 | 1.66856E-05 | None | 0 | 0 | None | 0 | 0 | 9.32777E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.1739 | likely_benign | 0.1292 | benign | -0.883 | Destabilizing | 0.001 | N | 0.306 | neutral | N | 0.412871489 | None | None | N |
| P/C | 0.7394 | likely_pathogenic | 0.7363 | pathogenic | -0.689 | Destabilizing | 0.973 | D | 0.765 | deleterious | None | None | None | None | N |
| P/D | 0.9498 | likely_pathogenic | 0.9372 | pathogenic | -0.806 | Destabilizing | 0.826 | D | 0.676 | prob.neutral | None | None | None | None | N |
| P/E | 0.9076 | likely_pathogenic | 0.8842 | pathogenic | -0.885 | Destabilizing | 0.826 | D | 0.629 | neutral | None | None | None | None | N |
| P/F | 0.9506 | likely_pathogenic | 0.9418 | pathogenic | -0.839 | Destabilizing | 0.826 | D | 0.774 | deleterious | None | None | None | None | N |
| P/G | 0.6942 | likely_pathogenic | 0.6284 | pathogenic | -1.088 | Destabilizing | 0.404 | N | 0.601 | neutral | None | None | None | None | N |
| P/H | 0.8792 | likely_pathogenic | 0.8412 | pathogenic | -0.597 | Destabilizing | 0.991 | D | 0.74 | deleterious | None | None | None | None | N |
| P/I | 0.7332 | likely_pathogenic | 0.704 | pathogenic | -0.464 | Destabilizing | 0.45 | N | 0.702 | prob.neutral | None | None | None | None | N |
| P/K | 0.9458 | likely_pathogenic | 0.9369 | pathogenic | -0.888 | Destabilizing | 0.826 | D | 0.626 | neutral | None | None | None | None | N |
| P/L | 0.6234 | likely_pathogenic | 0.5867 | pathogenic | -0.464 | Destabilizing | 0.338 | N | 0.638 | neutral | N | 0.423704558 | None | None | N |
| P/M | 0.7635 | likely_pathogenic | 0.7406 | pathogenic | -0.412 | Destabilizing | 0.947 | D | 0.739 | prob.delet. | None | None | None | None | N |
| P/N | 0.8769 | likely_pathogenic | 0.8423 | pathogenic | -0.589 | Destabilizing | 0.906 | D | 0.744 | deleterious | None | None | None | None | N |
| P/Q | 0.8207 | likely_pathogenic | 0.7634 | pathogenic | -0.835 | Destabilizing | 0.879 | D | 0.702 | prob.neutral | N | 0.463164237 | None | None | N |
| P/R | 0.9128 | likely_pathogenic | 0.8889 | pathogenic | -0.284 | Destabilizing | 0.782 | D | 0.741 | deleterious | D | 0.522423184 | None | None | N |
| P/S | 0.5584 | ambiguous | 0.4585 | ambiguous | -0.969 | Destabilizing | 0.338 | N | 0.555 | neutral | N | 0.469204775 | None | None | N |
| P/T | 0.4278 | ambiguous | 0.3621 | ambiguous | -0.951 | Destabilizing | 0.338 | N | 0.572 | neutral | N | 0.459603857 | None | None | N |
| P/V | 0.4956 | ambiguous | 0.4605 | ambiguous | -0.568 | Destabilizing | 0.01 | N | 0.457 | neutral | None | None | None | None | N |
| P/W | 0.9798 | likely_pathogenic | 0.9769 | pathogenic | -0.946 | Destabilizing | 0.991 | D | 0.722 | prob.delet. | None | None | None | None | N |
| P/Y | 0.9418 | likely_pathogenic | 0.9282 | pathogenic | -0.679 | Destabilizing | 0.906 | D | 0.775 | 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.