Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22778 | 68557;68558;68559 | chr2:178578183;178578182;178578181 | chr2:179442910;179442909;179442908 |
| N2AB | 21137 | 63634;63635;63636 | chr2:178578183;178578182;178578181 | chr2:179442910;179442909;179442908 |
| N2A | 20210 | 60853;60854;60855 | chr2:178578183;178578182;178578181 | chr2:179442910;179442909;179442908 |
| N2B | 13713 | 41362;41363;41364 | chr2:178578183;178578182;178578181 | chr2:179442910;179442909;179442908 |
| Novex-1 | 13838 | 41737;41738;41739 | chr2:178578183;178578182;178578181 | chr2:179442910;179442909;179442908 |
| Novex-2 | 13905 | 41938;41939;41940 | chr2:178578183;178578182;178578181 | chr2:179442910;179442909;179442908 |
| 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/C | rs1331107431  |
None | 1.0 | D | 0.861 | 0.784 | 0.866710377902 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| Y/C | rs1331107431 |
None | 1.0 | D | 0.861 | 0.784 | 0.866710377902 | gnomAD-4.0.0 | 2.57183E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.39653E-06 | 1.34372E-05 | 0 |
| Y/H | rs376535279 |
-2.856 | 1.0 | D | 0.821 | 0.806 | 0.743984732499 | gnomAD-2.1.1 | 4.07E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.61E-05 | None | 0 | None | 0 | 0 | 0 |
| Y/H | rs376535279 |
-2.856 | 1.0 | D | 0.821 | 0.806 | 0.743984732499 | gnomAD-4.0.0 | 1.59983E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77932E-05 | 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 | -3.402 | Highly Destabilizing | 1.0 | D | 0.826 | deleterious | None | None | None | None | N |
| Y/C | 0.9056 | likely_pathogenic | 0.8979 | pathogenic | -1.803 | Destabilizing | 1.0 | D | 0.861 | deleterious | D | 0.669067714 | None | None | N |
| Y/D | 0.9978 | likely_pathogenic | 0.9978 | pathogenic | -3.911 | Highly Destabilizing | 1.0 | D | 0.913 | deleterious | D | 0.669269518 | None | None | N |
| Y/E | 0.9992 | likely_pathogenic | 0.9992 | pathogenic | -3.694 | Highly Destabilizing | 1.0 | D | 0.901 | deleterious | None | None | None | None | N |
| Y/F | 0.1982 | likely_benign | 0.1655 | benign | -1.457 | Destabilizing | 0.999 | D | 0.647 | neutral | D | 0.571842522 | None | None | N |
| Y/G | 0.9925 | likely_pathogenic | 0.9923 | pathogenic | -3.803 | Highly Destabilizing | 1.0 | D | 0.924 | deleterious | None | None | None | None | N |
| Y/H | 0.9656 | likely_pathogenic | 0.9646 | pathogenic | -2.603 | Highly Destabilizing | 1.0 | D | 0.821 | deleterious | D | 0.643125994 | None | None | N |
| Y/I | 0.9718 | likely_pathogenic | 0.9704 | pathogenic | -2.04 | Highly Destabilizing | 1.0 | D | 0.866 | deleterious | None | None | None | None | N |
| Y/K | 0.9983 | likely_pathogenic | 0.9985 | pathogenic | -2.589 | Highly Destabilizing | 1.0 | D | 0.896 | deleterious | None | None | None | None | N |
| Y/L | 0.9524 | likely_pathogenic | 0.9546 | pathogenic | -2.04 | Highly Destabilizing | 0.999 | D | 0.759 | deleterious | None | None | None | None | N |
| Y/M | 0.9847 | likely_pathogenic | 0.9826 | pathogenic | -1.666 | Destabilizing | 1.0 | D | 0.839 | deleterious | None | None | None | None | N |
| Y/N | 0.9821 | likely_pathogenic | 0.9828 | pathogenic | -3.44 | Highly Destabilizing | 1.0 | D | 0.891 | deleterious | D | 0.669067714 | None | None | N |
| Y/P | 0.9995 | likely_pathogenic | 0.9994 | pathogenic | -2.514 | Highly Destabilizing | 1.0 | D | 0.939 | deleterious | None | None | None | None | N |
| Y/Q | 0.9978 | likely_pathogenic | 0.9978 | pathogenic | -3.151 | Highly Destabilizing | 1.0 | D | 0.852 | deleterious | None | None | None | None | N |
| Y/R | 0.9932 | likely_pathogenic | 0.9938 | pathogenic | -2.407 | Highly Destabilizing | 1.0 | D | 0.89 | deleterious | None | None | None | None | N |
| Y/S | 0.9867 | likely_pathogenic | 0.9873 | pathogenic | -3.681 | Highly Destabilizing | 1.0 | D | 0.901 | deleterious | D | 0.669067714 | None | None | N |
| Y/T | 0.996 | likely_pathogenic | 0.9963 | pathogenic | -3.348 | Highly Destabilizing | 1.0 | D | 0.901 | deleterious | None | None | None | None | N |
| Y/V | 0.9622 | likely_pathogenic | 0.9602 | pathogenic | -2.514 | Highly Destabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | N |
| Y/W | 0.7761 | likely_pathogenic | 0.7645 | pathogenic | -0.754 | Destabilizing | 1.0 | D | 0.805 | 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.