Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15990 | 48193;48194;48195 | chr2:178616921;178616920;178616919 | chr2:179481648;179481647;179481646 |
| N2AB | 14349 | 43270;43271;43272 | chr2:178616921;178616920;178616919 | chr2:179481648;179481647;179481646 |
| N2A | 13422 | 40489;40490;40491 | chr2:178616921;178616920;178616919 | chr2:179481648;179481647;179481646 |
| N2B | 6925 | 20998;20999;21000 | chr2:178616921;178616920;178616919 | chr2:179481648;179481647;179481646 |
| Novex-1 | 7050 | 21373;21374;21375 | chr2:178616921;178616920;178616919 | chr2:179481648;179481647;179481646 |
| Novex-2 | 7117 | 21574;21575;21576 | chr2:178616921;178616920;178616919 | chr2:179481648;179481647;179481646 |
| 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 | rs1253292798  |
-0.084 | 1.0 | D | 0.761 | 0.65 | 0.787459768874 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.96E-06 | 0 |
| P/L | rs1253292798 |
-0.084 | 1.0 | D | 0.761 | 0.65 | 0.787459768874 | gnomAD-4.0.0 | 1.59339E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86248E-06 | 0 | 0 |
| P/T | rs2057439809 |
None | 1.0 | D | 0.744 | 0.697 | 0.618957995044 | gnomAD-3.1.2 | 6.59E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| P/T | rs2057439809 |
None | 1.0 | D | 0.744 | 0.697 | 0.618957995044 | gnomAD-4.0.0 | 6.58597E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47284E-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 | 0.9409 | likely_pathogenic | 0.9625 | pathogenic | -0.958 | Destabilizing | 1.0 | D | 0.724 | prob.delet. | D | 0.721556792 | None | None | I |
| P/C | 0.992 | likely_pathogenic | 0.9951 | pathogenic | -0.646 | Destabilizing | 1.0 | D | 0.793 | deleterious | None | None | None | None | I |
| P/D | 0.9822 | likely_pathogenic | 0.9892 | pathogenic | -0.646 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | I |
| P/E | 0.9573 | likely_pathogenic | 0.9755 | pathogenic | -0.7 | Destabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | I |
| P/F | 0.9958 | likely_pathogenic | 0.9974 | pathogenic | -0.885 | Destabilizing | 1.0 | D | 0.818 | deleterious | None | None | None | None | I |
| P/G | 0.9738 | likely_pathogenic | 0.9809 | pathogenic | -1.182 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | I |
| P/H | 0.9765 | likely_pathogenic | 0.9856 | pathogenic | -0.72 | Destabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | I |
| P/I | 0.9741 | likely_pathogenic | 0.9833 | pathogenic | -0.478 | Destabilizing | 1.0 | D | 0.813 | deleterious | None | None | None | None | I |
| P/K | 0.9748 | likely_pathogenic | 0.9827 | pathogenic | -0.84 | Destabilizing | 1.0 | D | 0.744 | deleterious | None | None | None | None | I |
| P/L | 0.9276 | likely_pathogenic | 0.9523 | pathogenic | -0.478 | Destabilizing | 1.0 | D | 0.761 | deleterious | D | 0.700629325 | None | None | I |
| P/M | 0.9855 | likely_pathogenic | 0.9906 | pathogenic | -0.456 | Destabilizing | 1.0 | D | 0.788 | deleterious | None | None | None | None | I |
| P/N | 0.9848 | likely_pathogenic | 0.9902 | pathogenic | -0.552 | Destabilizing | 1.0 | D | 0.785 | deleterious | None | None | None | None | I |
| P/Q | 0.9541 | likely_pathogenic | 0.9704 | pathogenic | -0.74 | Destabilizing | 1.0 | D | 0.779 | deleterious | D | 0.721556792 | None | None | I |
| P/R | 0.9354 | likely_pathogenic | 0.9562 | pathogenic | -0.325 | Destabilizing | 1.0 | D | 0.791 | deleterious | D | 0.722052835 | None | None | I |
| P/S | 0.9752 | likely_pathogenic | 0.986 | pathogenic | -0.967 | Destabilizing | 1.0 | D | 0.748 | deleterious | D | 0.720334207 | None | None | I |
| P/T | 0.9458 | likely_pathogenic | 0.9685 | pathogenic | -0.916 | Destabilizing | 1.0 | D | 0.744 | deleterious | D | 0.722052835 | None | None | I |
| P/V | 0.9563 | likely_pathogenic | 0.9715 | pathogenic | -0.603 | Destabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | I |
| P/W | 0.9974 | likely_pathogenic | 0.9984 | pathogenic | -1.021 | Destabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | None | I |
| P/Y | 0.9936 | likely_pathogenic | 0.996 | pathogenic | -0.735 | Destabilizing | 1.0 | D | 0.829 | 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.