Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21891 | 65896;65897;65898 | chr2:178583132;178583131;178583130 | chr2:179447859;179447858;179447857 |
| N2AB | 20250 | 60973;60974;60975 | chr2:178583132;178583131;178583130 | chr2:179447859;179447858;179447857 |
| N2A | 19323 | 58192;58193;58194 | chr2:178583132;178583131;178583130 | chr2:179447859;179447858;179447857 |
| N2B | 12826 | 38701;38702;38703 | chr2:178583132;178583131;178583130 | chr2:179447859;179447858;179447857 |
| Novex-1 | 12951 | 39076;39077;39078 | chr2:178583132;178583131;178583130 | chr2:179447859;179447858;179447857 |
| Novex-2 | 13018 | 39277;39278;39279 | chr2:178583132;178583131;178583130 | chr2:179447859;179447858;179447857 |
| 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/L | rs397517662  |
0.086 | 1.0 | D | 0.759 | 0.653 | None | gnomAD-2.1.1 | 5.4E-05 | None | None | None | None | I | None | 4.15E-05 | 1.706E-04 | None | 0 | 0 | None | 0 | None | 0 | 5.52E-05 | 1.41804E-04 |
| P/L | rs397517662 |
0.086 | 1.0 | D | 0.759 | 0.653 | None | gnomAD-3.1.2 | 8.56E-05 | None | None | None | None | I | None | 2.42E-05 | 3.93391E-04 | 0 | 0 | 0 | None | 0 | 0 | 5.89E-05 | 0 | 9.58773E-04 |
| P/L | rs397517662 |
0.086 | 1.0 | D | 0.759 | 0.653 | None | gnomAD-4.0.0 | 5.08679E-05 | None | None | None | None | I | None | 1.33679E-05 | 2.17108E-04 | None | 0 | 0 | None | 0 | 1.6469E-04 | 4.58014E-05 | 3.2991E-05 | 1.60339E-04 |
| P/Q | rs397517662 |
-0.142 | 1.0 | D | 0.759 | 0.733 | 0.763579139685 | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | I | None | 0 | 2.91E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| P/Q | rs397517662 |
-0.142 | 1.0 | D | 0.759 | 0.733 | 0.763579139685 | gnomAD-4.0.0 | 1.36979E-06 | None | None | None | None | I | None | 0 | 4.48169E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/S | None | None | 1.0 | D | 0.745 | 0.744 | 0.59105502098 | gnomAD-4.0.0 | 6.84839E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99993E-07 | 0 | 0 |
| P/T | rs1446139113 |
-0.265 | 1.0 | D | 0.745 | 0.752 | 0.759977468783 | gnomAD-2.1.1 | 7.19E-06 | None | None | None | None | I | None | 4.15E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 7.89E-06 | 0 |
| P/T | rs1446139113 |
-0.265 | 1.0 | D | 0.745 | 0.752 | 0.759977468783 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/T | rs1446139113 |
-0.265 | 1.0 | D | 0.745 | 0.752 | 0.759977468783 | gnomAD-4.0.0 | 1.36462E-05 | None | None | None | None | I | None | 2.67358E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.69623E-05 | 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 | 0.9646 | likely_pathogenic | 0.962 | pathogenic | -0.497 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | D | 0.547795407 | None | None | I |
| P/C | 0.9972 | likely_pathogenic | 0.9964 | pathogenic | -0.553 | Destabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | None | I |
| P/D | 0.9876 | likely_pathogenic | 0.9855 | pathogenic | -0.371 | Destabilizing | 1.0 | D | 0.742 | deleterious | None | None | None | None | I |
| P/E | 0.9878 | likely_pathogenic | 0.9863 | pathogenic | -0.503 | Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | I |
| P/F | 0.9982 | likely_pathogenic | 0.9975 | pathogenic | -0.835 | Destabilizing | 1.0 | D | 0.8 | deleterious | None | None | None | None | I |
| P/G | 0.985 | likely_pathogenic | 0.9819 | pathogenic | -0.609 | Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | I |
| P/H | 0.9879 | likely_pathogenic | 0.9855 | pathogenic | -0.239 | Destabilizing | 1.0 | D | 0.785 | deleterious | None | None | None | None | I |
| P/I | 0.9854 | likely_pathogenic | 0.9841 | pathogenic | -0.359 | Destabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | I |
| P/K | 0.9889 | likely_pathogenic | 0.9863 | pathogenic | -0.4 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | I |
| P/L | 0.965 | likely_pathogenic | 0.9596 | pathogenic | -0.359 | Destabilizing | 1.0 | D | 0.759 | deleterious | D | 0.601563187 | None | None | I |
| P/M | 0.9898 | likely_pathogenic | 0.9882 | pathogenic | -0.291 | Destabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | I |
| P/N | 0.9878 | likely_pathogenic | 0.986 | pathogenic | -0.1 | Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | I |
| P/Q | 0.986 | likely_pathogenic | 0.9839 | pathogenic | -0.388 | Destabilizing | 1.0 | D | 0.759 | deleterious | D | 0.565899662 | None | None | I |
| P/R | 0.9779 | likely_pathogenic | 0.9737 | pathogenic | 0.146 | Stabilizing | 1.0 | D | 0.775 | deleterious | D | 0.610678329 | None | None | I |
| P/S | 0.9887 | likely_pathogenic | 0.9881 | pathogenic | -0.435 | Destabilizing | 1.0 | D | 0.745 | deleterious | D | 0.547288428 | None | None | I |
| P/T | 0.9706 | likely_pathogenic | 0.9681 | pathogenic | -0.471 | Destabilizing | 1.0 | D | 0.745 | deleterious | D | 0.610678329 | None | None | I |
| P/V | 0.9722 | likely_pathogenic | 0.9692 | pathogenic | -0.371 | Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | I |
| P/W | 0.9987 | likely_pathogenic | 0.9983 | pathogenic | -0.899 | Destabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | I |
| P/Y | 0.9957 | likely_pathogenic | 0.9939 | pathogenic | -0.596 | Destabilizing | 1.0 | D | 0.809 | deleterious | None | None | 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.