Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28451 | 85576;85577;85578 | chr2:178560781;178560780;178560779 | chr2:179425508;179425507;179425506 |
| N2AB | 26810 | 80653;80654;80655 | chr2:178560781;178560780;178560779 | chr2:179425508;179425507;179425506 |
| N2A | 25883 | 77872;77873;77874 | chr2:178560781;178560780;178560779 | chr2:179425508;179425507;179425506 |
| N2B | 19386 | 58381;58382;58383 | chr2:178560781;178560780;178560779 | chr2:179425508;179425507;179425506 |
| Novex-1 | 19511 | 58756;58757;58758 | chr2:178560781;178560780;178560779 | chr2:179425508;179425507;179425506 |
| Novex-2 | 19578 | 58957;58958;58959 | chr2:178560781;178560780;178560779 | chr2:179425508;179425507;179425506 |
| 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/S | rs727503554  |
-2.495 | 1.0 | D | 0.799 | 0.512 | 0.570337063641 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 1.14732E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| P/S | rs727503554 |
-2.495 | 1.0 | D | 0.799 | 0.512 | 0.570337063641 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/S | rs727503554 |
-2.495 | 1.0 | D | 0.799 | 0.512 | 0.570337063641 | gnomAD-4.0.0 | 3.09865E-06 | None | None | None | None | N | None | 6.67414E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.7846 | likely_pathogenic | 0.8173 | pathogenic | -1.637 | Destabilizing | 0.999 | D | 0.841 | deleterious | D | 0.524111387 | None | None | N |
| P/C | 0.9786 | likely_pathogenic | 0.986 | pathogenic | -1.911 | Destabilizing | 1.0 | D | 0.802 | deleterious | None | None | None | None | N |
| P/D | 0.9952 | likely_pathogenic | 0.998 | pathogenic | -3.27 | Highly Destabilizing | 1.0 | D | 0.814 | deleterious | None | None | None | None | N |
| P/E | 0.9884 | likely_pathogenic | 0.9947 | pathogenic | -3.2 | Highly Destabilizing | 1.0 | D | 0.807 | deleterious | None | None | None | None | N |
| P/F | 0.9975 | likely_pathogenic | 0.9985 | pathogenic | -1.094 | Destabilizing | 1.0 | D | 0.828 | deleterious | None | None | None | None | N |
| P/G | 0.9821 | likely_pathogenic | 0.9891 | pathogenic | -1.973 | Destabilizing | 1.0 | D | 0.827 | deleterious | None | None | None | None | N |
| P/H | 0.9856 | likely_pathogenic | 0.9932 | pathogenic | -1.402 | Destabilizing | 1.0 | D | 0.795 | deleterious | D | 0.551876881 | None | None | N |
| P/I | 0.9639 | likely_pathogenic | 0.9696 | pathogenic | -0.76 | Destabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | None | N |
| P/K | 0.9881 | likely_pathogenic | 0.9951 | pathogenic | -1.521 | Destabilizing | 1.0 | D | 0.807 | deleterious | None | None | None | None | N |
| P/L | 0.8811 | likely_pathogenic | 0.9141 | pathogenic | -0.76 | Destabilizing | 1.0 | D | 0.835 | deleterious | D | 0.540355991 | None | None | N |
| P/M | 0.983 | likely_pathogenic | 0.9879 | pathogenic | -0.975 | Destabilizing | 1.0 | D | 0.792 | deleterious | None | None | None | None | N |
| P/N | 0.9947 | likely_pathogenic | 0.9974 | pathogenic | -1.812 | Destabilizing | 1.0 | D | 0.85 | deleterious | None | None | None | None | N |
| P/Q | 0.9816 | likely_pathogenic | 0.9902 | pathogenic | -1.949 | Destabilizing | 1.0 | D | 0.835 | deleterious | None | None | None | None | N |
| P/R | 0.9635 | likely_pathogenic | 0.9835 | pathogenic | -1.061 | Destabilizing | 1.0 | D | 0.847 | deleterious | D | 0.551116412 | None | None | N |
| P/S | 0.9653 | likely_pathogenic | 0.9772 | pathogenic | -2.145 | Highly Destabilizing | 1.0 | D | 0.799 | deleterious | D | 0.550102454 | None | None | N |
| P/T | 0.9309 | likely_pathogenic | 0.9535 | pathogenic | -1.975 | Destabilizing | 1.0 | D | 0.803 | deleterious | D | 0.551116412 | None | None | N |
| P/V | 0.9211 | likely_pathogenic | 0.9314 | pathogenic | -1.026 | Destabilizing | 1.0 | D | 0.854 | deleterious | None | None | None | None | N |
| P/W | 0.998 | likely_pathogenic | 0.9991 | pathogenic | -1.446 | Destabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | N |
| P/Y | 0.9953 | likely_pathogenic | 0.9974 | pathogenic | -1.135 | Destabilizing | 1.0 | D | 0.837 | 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.