Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16056 | 48391;48392;48393 | chr2:178616625;178616624;178616623 | chr2:179481352;179481351;179481350 |
| N2AB | 14415 | 43468;43469;43470 | chr2:178616625;178616624;178616623 | chr2:179481352;179481351;179481350 |
| N2A | 13488 | 40687;40688;40689 | chr2:178616625;178616624;178616623 | chr2:179481352;179481351;179481350 |
| N2B | 6991 | 21196;21197;21198 | chr2:178616625;178616624;178616623 | chr2:179481352;179481351;179481350 |
| Novex-1 | 7116 | 21571;21572;21573 | chr2:178616625;178616624;178616623 | chr2:179481352;179481351;179481350 |
| Novex-2 | 7183 | 21772;21773;21774 | chr2:178616625;178616624;178616623 | chr2:179481352;179481351;179481350 |
| 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 | rs752993848  |
-0.247 | 1.0 | D | 0.822 | 0.764 | None | gnomAD-2.1.1 | 8.25E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 1.60385E-04 | 1.4924E-04 | 0 |
| P/L | rs752993848 |
-0.247 | 1.0 | D | 0.822 | 0.764 | None | gnomAD-3.1.2 | 6.59E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 9.45E-05 | 0 | 0 | 0 | 0 |
| P/L | rs752993848 |
-0.247 | 1.0 | D | 0.822 | 0.764 | None | gnomAD-4.0.0 | 2.29556E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 7.81959E-05 | 0 | 2.37508E-05 | 0 | 6.41519E-05 |
| P/S | rs2057390140 |
None | 1.0 | D | 0.733 | 0.818 | 0.759536342175 | gnomAD-4.0.0 | 1.59508E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43571E-05 | 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 | 0.909 | likely_pathogenic | 0.9444 | pathogenic | -1.313 | Destabilizing | 0.999 | D | 0.802 | deleterious | D | 0.735777754 | None | None | N |
| P/C | 0.988 | likely_pathogenic | 0.9935 | pathogenic | -1.992 | Destabilizing | 1.0 | D | 0.807 | deleterious | None | None | None | None | N |
| P/D | 0.999 | likely_pathogenic | 0.9992 | pathogenic | -3.437 | Highly Destabilizing | 1.0 | D | 0.758 | deleterious | None | None | None | None | N |
| P/E | 0.9976 | likely_pathogenic | 0.9981 | pathogenic | -3.351 | Highly Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | N |
| P/F | 0.9994 | likely_pathogenic | 0.9996 | pathogenic | -0.769 | Destabilizing | 1.0 | D | 0.835 | deleterious | None | None | None | None | N |
| P/G | 0.9906 | likely_pathogenic | 0.9937 | pathogenic | -1.634 | Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | N |
| P/H | 0.9969 | likely_pathogenic | 0.9979 | pathogenic | -1.153 | Destabilizing | 1.0 | D | 0.779 | deleterious | None | None | None | None | N |
| P/I | 0.9926 | likely_pathogenic | 0.9959 | pathogenic | -0.471 | Destabilizing | 1.0 | D | 0.783 | deleterious | None | None | None | None | N |
| P/K | 0.9984 | likely_pathogenic | 0.9989 | pathogenic | -1.449 | Destabilizing | 1.0 | D | 0.75 | deleterious | None | None | None | None | N |
| P/L | 0.9781 | likely_pathogenic | 0.9872 | pathogenic | -0.471 | Destabilizing | 1.0 | D | 0.822 | deleterious | D | 0.769993401 | None | None | N |
| P/M | 0.9967 | likely_pathogenic | 0.9982 | pathogenic | -0.822 | Destabilizing | 1.0 | D | 0.778 | deleterious | None | None | None | None | N |
| P/N | 0.9982 | likely_pathogenic | 0.9988 | pathogenic | -1.922 | Destabilizing | 1.0 | D | 0.824 | deleterious | None | None | None | None | N |
| P/Q | 0.9952 | likely_pathogenic | 0.9966 | pathogenic | -1.991 | Destabilizing | 1.0 | D | 0.807 | deleterious | D | 0.802461889 | None | None | N |
| P/R | 0.9932 | likely_pathogenic | 0.9951 | pathogenic | -1.093 | Destabilizing | 1.0 | D | 0.819 | deleterious | D | 0.803018286 | None | None | N |
| P/S | 0.9845 | likely_pathogenic | 0.9909 | pathogenic | -2.147 | Highly Destabilizing | 1.0 | D | 0.733 | deleterious | D | 0.802937273 | None | None | N |
| P/T | 0.9817 | likely_pathogenic | 0.9895 | pathogenic | -1.964 | Destabilizing | 1.0 | D | 0.741 | deleterious | D | 0.750190133 | None | None | N |
| P/V | 0.9748 | likely_pathogenic | 0.9862 | pathogenic | -0.727 | Destabilizing | 1.0 | D | 0.817 | deleterious | None | None | None | None | N |
| P/W | 0.9997 | likely_pathogenic | 0.9998 | pathogenic | -1.221 | Destabilizing | 1.0 | D | 0.766 | deleterious | None | None | None | None | N |
| P/Y | 0.9992 | likely_pathogenic | 0.9994 | pathogenic | -0.889 | Destabilizing | 1.0 | D | 0.843 | 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.