Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23275 | 70048;70049;70050 | chr2:178576309;178576308;178576307 | chr2:179441036;179441035;179441034 |
| N2AB | 21634 | 65125;65126;65127 | chr2:178576309;178576308;178576307 | chr2:179441036;179441035;179441034 |
| N2A | 20707 | 62344;62345;62346 | chr2:178576309;178576308;178576307 | chr2:179441036;179441035;179441034 |
| N2B | 14210 | 42853;42854;42855 | chr2:178576309;178576308;178576307 | chr2:179441036;179441035;179441034 |
| Novex-1 | 14335 | 43228;43229;43230 | chr2:178576309;178576308;178576307 | chr2:179441036;179441035;179441034 |
| Novex-2 | 14402 | 43429;43430;43431 | chr2:178576309;178576308;178576307 | chr2:179441036;179441035;179441034 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/H | rs267599039  |
None | 1.0 | D | 0.813 | 0.783 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| Y/H | rs267599039 |
None | 1.0 | D | 0.813 | 0.783 | None | gnomAD-4.0.0 | 1.31501E-05 | None | None | None | None | N | None | 4.82602E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| Y/N | rs267599039 |
-3.014 | 1.0 | D | 0.891 | 0.803 | 0.908585532488 | gnomAD-2.1.1 | 4.71E-06 | None | None | None | None | N | None | 0 | 3.58E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| Y/N | rs267599039 |
-3.014 | 1.0 | D | 0.891 | 0.803 | 0.908585532488 | gnomAD-4.0.0 | 1.68852E-06 | None | None | None | None | N | None | 0 | 2.72331E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.9972 | likely_pathogenic | 0.997 | pathogenic | -3.357 | Highly Destabilizing | 1.0 | D | 0.806 | deleterious | None | None | None | None | N |
| Y/C | 0.9452 | likely_pathogenic | 0.9397 | pathogenic | -1.723 | Destabilizing | 1.0 | D | 0.867 | deleterious | D | 0.650726706 | None | None | N |
| Y/D | 0.9955 | likely_pathogenic | 0.995 | pathogenic | -3.729 | Highly Destabilizing | 1.0 | D | 0.903 | deleterious | D | 0.650928511 | None | None | N |
| Y/E | 0.9989 | likely_pathogenic | 0.9989 | pathogenic | -3.502 | Highly Destabilizing | 1.0 | D | 0.891 | deleterious | None | None | None | None | N |
| Y/F | 0.3088 | likely_benign | 0.3538 | ambiguous | -1.338 | Destabilizing | 0.999 | D | 0.665 | neutral | D | 0.5627881 | None | None | N |
| Y/G | 0.9915 | likely_pathogenic | 0.991 | pathogenic | -3.778 | Highly Destabilizing | 1.0 | D | 0.908 | deleterious | None | None | None | None | N |
| Y/H | 0.9865 | likely_pathogenic | 0.9864 | pathogenic | -2.493 | Highly Destabilizing | 1.0 | D | 0.813 | deleterious | D | 0.634303737 | None | None | N |
| Y/I | 0.9783 | likely_pathogenic | 0.9785 | pathogenic | -1.933 | Destabilizing | 1.0 | D | 0.835 | deleterious | None | None | None | None | N |
| Y/K | 0.9988 | likely_pathogenic | 0.9987 | pathogenic | -2.409 | Highly Destabilizing | 1.0 | D | 0.887 | deleterious | None | None | None | None | N |
| Y/L | 0.9574 | likely_pathogenic | 0.9556 | pathogenic | -1.933 | Destabilizing | 0.999 | D | 0.733 | prob.delet. | None | None | None | None | N |
| Y/M | 0.9854 | likely_pathogenic | 0.9856 | pathogenic | -1.583 | Destabilizing | 1.0 | D | 0.821 | deleterious | None | None | None | None | N |
| Y/N | 0.977 | likely_pathogenic | 0.976 | pathogenic | -3.258 | Highly Destabilizing | 1.0 | D | 0.891 | deleterious | D | 0.650726706 | None | None | N |
| Y/P | 0.9993 | likely_pathogenic | 0.9991 | pathogenic | -2.428 | Highly Destabilizing | 1.0 | D | 0.923 | deleterious | None | None | None | None | N |
| Y/Q | 0.9988 | likely_pathogenic | 0.9987 | pathogenic | -2.959 | Highly Destabilizing | 1.0 | D | 0.835 | deleterious | None | None | None | None | N |
| Y/R | 0.9958 | likely_pathogenic | 0.9955 | pathogenic | -2.253 | Highly Destabilizing | 1.0 | D | 0.887 | deleterious | None | None | None | None | N |
| Y/S | 0.9889 | likely_pathogenic | 0.9879 | pathogenic | -3.552 | Highly Destabilizing | 1.0 | D | 0.888 | deleterious | D | 0.634707345 | None | None | N |
| Y/T | 0.9958 | likely_pathogenic | 0.9955 | pathogenic | -3.202 | Highly Destabilizing | 1.0 | D | 0.891 | deleterious | None | None | None | None | N |
| Y/V | 0.9652 | likely_pathogenic | 0.9652 | pathogenic | -2.428 | Highly Destabilizing | 1.0 | D | 0.756 | deleterious | None | None | None | None | N |
| Y/W | 0.8819 | likely_pathogenic | 0.8692 | pathogenic | -0.564 | Destabilizing | 1.0 | D | 0.799 | 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.