Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26799 | 80620;80621;80622 | chr2:178565737;178565736;178565735 | chr2:179430464;179430463;179430462 |
| N2AB | 25158 | 75697;75698;75699 | chr2:178565737;178565736;178565735 | chr2:179430464;179430463;179430462 |
| N2A | 24231 | 72916;72917;72918 | chr2:178565737;178565736;178565735 | chr2:179430464;179430463;179430462 |
| N2B | 17734 | 53425;53426;53427 | chr2:178565737;178565736;178565735 | chr2:179430464;179430463;179430462 |
| Novex-1 | 17859 | 53800;53801;53802 | chr2:178565737;178565736;178565735 | chr2:179430464;179430463;179430462 |
| Novex-2 | 17926 | 54001;54002;54003 | chr2:178565737;178565736;178565735 | chr2:179430464;179430463;179430462 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/F | rs781537985  |
-1.628 | 0.208 | D | 0.367 | 0.315 | 0.44389696681 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| L/F | rs781537985 |
-1.628 | 0.208 | D | 0.367 | 0.315 | 0.44389696681 | gnomAD-4.0.0 | 1.59169E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85933E-06 | 0 | 0 |
| L/R | rs1236098527 |
-1.888 | 1.0 | D | 0.863 | 0.69 | 0.852974075071 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| L/R | rs1236098527 |
-1.888 | 1.0 | D | 0.863 | 0.69 | 0.852974075071 | gnomAD-4.0.0 | 6.1586E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.09615E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.9697 | likely_pathogenic | 0.963 | pathogenic | -2.577 | Highly Destabilizing | 0.998 | D | 0.673 | neutral | None | None | None | None | N |
| L/C | 0.9433 | likely_pathogenic | 0.9204 | pathogenic | -2.005 | Highly Destabilizing | 1.0 | D | 0.746 | deleterious | None | None | None | None | N |
| L/D | 0.9995 | likely_pathogenic | 0.9994 | pathogenic | -2.977 | Highly Destabilizing | 1.0 | D | 0.887 | deleterious | None | None | None | None | N |
| L/E | 0.9968 | likely_pathogenic | 0.9963 | pathogenic | -2.647 | Highly Destabilizing | 1.0 | D | 0.877 | deleterious | None | None | None | None | N |
| L/F | 0.3725 | ambiguous | 0.2004 | benign | -1.569 | Destabilizing | 0.208 | N | 0.367 | neutral | D | 0.526087894 | None | None | N |
| L/G | 0.9955 | likely_pathogenic | 0.9944 | pathogenic | -3.218 | Highly Destabilizing | 1.0 | D | 0.867 | deleterious | None | None | None | None | N |
| L/H | 0.9891 | likely_pathogenic | 0.9847 | pathogenic | -2.981 | Highly Destabilizing | 1.0 | D | 0.879 | deleterious | D | 0.559956227 | None | None | N |
| L/I | 0.1216 | likely_benign | 0.1127 | benign | -0.664 | Destabilizing | 0.757 | D | 0.599 | neutral | D | 0.526413213 | None | None | N |
| L/K | 0.9934 | likely_pathogenic | 0.993 | pathogenic | -1.908 | Destabilizing | 1.0 | D | 0.842 | deleterious | None | None | None | None | N |
| L/M | 0.3299 | likely_benign | 0.2787 | benign | -0.901 | Destabilizing | 0.996 | D | 0.666 | neutral | None | None | None | None | N |
| L/N | 0.9975 | likely_pathogenic | 0.9972 | pathogenic | -2.567 | Highly Destabilizing | 1.0 | D | 0.889 | deleterious | None | None | None | None | N |
| L/P | 0.9958 | likely_pathogenic | 0.9957 | pathogenic | -1.29 | Destabilizing | 1.0 | D | 0.89 | deleterious | D | 0.559956227 | None | None | N |
| L/Q | 0.9885 | likely_pathogenic | 0.9867 | pathogenic | -2.187 | Highly Destabilizing | 1.0 | D | 0.876 | deleterious | None | None | None | None | N |
| L/R | 0.9855 | likely_pathogenic | 0.9845 | pathogenic | -2.048 | Highly Destabilizing | 1.0 | D | 0.863 | deleterious | D | 0.559956227 | None | None | N |
| L/S | 0.9958 | likely_pathogenic | 0.9948 | pathogenic | -3.242 | Highly Destabilizing | 1.0 | D | 0.828 | deleterious | None | None | None | None | N |
| L/T | 0.9797 | likely_pathogenic | 0.9779 | pathogenic | -2.728 | Highly Destabilizing | 0.998 | D | 0.699 | prob.neutral | None | None | None | None | N |
| L/V | 0.1986 | likely_benign | 0.1921 | benign | -1.29 | Destabilizing | 0.891 | D | 0.632 | neutral | N | 0.476803742 | None | None | N |
| L/W | 0.9231 | likely_pathogenic | 0.8579 | pathogenic | -1.958 | Destabilizing | 1.0 | D | 0.855 | deleterious | None | None | None | None | N |
| L/Y | 0.9438 | likely_pathogenic | 0.8994 | pathogenic | -1.69 | Destabilizing | 0.958 | D | 0.699 | prob.neutral | 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.