Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3350 | 10273;10274;10275 | chr2:178764243;178764242;178764241 | chr2:179628970;179628969;179628968 |
| N2AB | 3350 | 10273;10274;10275 | chr2:178764243;178764242;178764241 | chr2:179628970;179628969;179628968 |
| N2A | 3350 | 10273;10274;10275 | chr2:178764243;178764242;178764241 | chr2:179628970;179628969;179628968 |
| N2B | 3304 | 10135;10136;10137 | chr2:178764243;178764242;178764241 | chr2:179628970;179628969;179628968 |
| Novex-1 | 3304 | 10135;10136;10137 | chr2:178764243;178764242;178764241 | chr2:179628970;179628969;179628968 |
| Novex-2 | 3304 | 10135;10136;10137 | chr2:178764243;178764242;178764241 | chr2:179628970;179628969;179628968 |
| Novex-3 | 3350 | 10273;10274;10275 | chr2:178764243;178764242;178764241 | chr2:179628970;179628969;179628968 |
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/L | rs139504522  |
-0.381 | 0.992 | D | 0.769 | 0.521 | None | gnomAD-2.1.1 | 1.8399E-04 | None | None | None | None | N | None | 1.562E-03 | 1.12924E-04 | None | 0 | 0 | None | 0 | None | 0 | 6.2E-05 | 1.38619E-04 |
| P/L | rs139504522 |
-0.381 | 0.992 | D | 0.769 | 0.521 | None | gnomAD-3.1.2 | 3.81153E-04 | None | None | None | None | N | None | 1.27927E-03 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 9.57854E-04 |
| P/L | rs139504522 |
-0.381 | 0.992 | D | 0.769 | 0.521 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| P/L | rs139504522 |
-0.381 | 0.992 | D | 0.769 | 0.521 | None | gnomAD-4.0.0 | 8.73562E-05 | None | None | None | None | N | None | 1.41277E-03 | 9.99833E-05 | None | 0 | 0 | None | 0 | 0 | 1.94918E-05 | 0 | 9.59939E-05 |
| P/Q | rs139504522 |
None | 0.996 | D | 0.809 | 0.468 | 0.573031010871 | gnomAD-4.0.0 | 1.36818E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99313E-07 | 0 | 1.65579E-05 |
| P/S | rs1192725293 |
None | 0.957 | N | 0.743 | 0.48 | 0.447901950027 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 | 0.1002 | likely_benign | 0.0977 | benign | -0.969 | Destabilizing | 0.865 | D | 0.623 | neutral | D | 0.522579635 | None | None | N |
| P/C | 0.7034 | likely_pathogenic | 0.6026 | pathogenic | -0.7 | Destabilizing | 0.999 | D | 0.78 | deleterious | None | None | None | None | N |
| P/D | 0.542 | ambiguous | 0.5834 | pathogenic | -0.726 | Destabilizing | 0.983 | D | 0.805 | deleterious | None | None | None | None | N |
| P/E | 0.3283 | likely_benign | 0.3503 | ambiguous | -0.813 | Destabilizing | 0.983 | D | 0.786 | deleterious | None | None | None | None | N |
| P/F | 0.6597 | likely_pathogenic | 0.6083 | pathogenic | -0.973 | Destabilizing | 0.998 | D | 0.789 | deleterious | None | None | None | None | N |
| P/G | 0.4106 | ambiguous | 0.4106 | ambiguous | -1.169 | Destabilizing | 0.983 | D | 0.723 | prob.delet. | None | None | None | None | N |
| P/H | 0.2594 | likely_benign | 0.2392 | benign | -0.704 | Destabilizing | 0.999 | D | 0.766 | deleterious | None | None | None | None | N |
| P/I | 0.503 | ambiguous | 0.4679 | ambiguous | -0.568 | Destabilizing | 0.983 | D | 0.8 | deleterious | None | None | None | None | N |
| P/K | 0.345 | ambiguous | 0.369 | ambiguous | -0.815 | Destabilizing | 0.983 | D | 0.801 | deleterious | None | None | None | None | N |
| P/L | 0.1851 | likely_benign | 0.1639 | benign | -0.568 | Destabilizing | 0.992 | D | 0.769 | deleterious | D | 0.570005716 | None | None | N |
| P/M | 0.4866 | ambiguous | 0.4473 | ambiguous | -0.42 | Destabilizing | 0.998 | D | 0.767 | deleterious | None | None | None | None | N |
| P/N | 0.4491 | ambiguous | 0.4647 | ambiguous | -0.533 | Destabilizing | 0.983 | D | 0.774 | deleterious | None | None | None | None | N |
| P/Q | 0.1944 | likely_benign | 0.2001 | benign | -0.799 | Destabilizing | 0.996 | D | 0.809 | deleterious | D | 0.522019364 | None | None | N |
| P/R | 0.2054 | likely_benign | 0.2065 | benign | -0.229 | Destabilizing | 0.991 | D | 0.786 | deleterious | N | 0.519444616 | None | None | N |
| P/S | 0.1435 | likely_benign | 0.1413 | benign | -0.943 | Destabilizing | 0.957 | D | 0.743 | deleterious | N | 0.516093521 | None | None | N |
| P/T | 0.1574 | likely_benign | 0.1523 | benign | -0.933 | Destabilizing | 0.085 | N | 0.339 | neutral | N | 0.514973619 | None | None | N |
| P/V | 0.3355 | likely_benign | 0.31 | benign | -0.666 | Destabilizing | 0.968 | D | 0.715 | prob.delet. | None | None | None | None | N |
| P/W | 0.8204 | likely_pathogenic | 0.7694 | pathogenic | -1.061 | Destabilizing | 0.999 | D | 0.781 | deleterious | None | None | None | None | N |
| P/Y | 0.5752 | likely_pathogenic | 0.536 | ambiguous | -0.785 | Destabilizing | 0.999 | D | 0.789 | 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.