Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24049 | 72370;72371;72372 | chr2:178573987;178573986;178573985 | chr2:179438714;179438713;179438712 |
| N2AB | 22408 | 67447;67448;67449 | chr2:178573987;178573986;178573985 | chr2:179438714;179438713;179438712 |
| N2A | 21481 | 64666;64667;64668 | chr2:178573987;178573986;178573985 | chr2:179438714;179438713;179438712 |
| N2B | 14984 | 45175;45176;45177 | chr2:178573987;178573986;178573985 | chr2:179438714;179438713;179438712 |
| Novex-1 | 15109 | 45550;45551;45552 | chr2:178573987;178573986;178573985 | chr2:179438714;179438713;179438712 |
| Novex-2 | 15176 | 45751;45752;45753 | chr2:178573987;178573986;178573985 | chr2:179438714;179438713;179438712 |
| 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/P | rs56399205  |
-0.764 | 1.0 | D | 0.853 | 0.863 | None | gnomAD-2.1.1 | 5.50799E-04 | None | None | None | None | N | None | 1.24059E-04 | 2.54929E-04 | None | 0 | 0 | None | 3.27E-05 | None | 1.59962E-04 | 1.02534E-03 | 8.44832E-04 |
| L/P | rs56399205 |
-0.764 | 1.0 | D | 0.853 | 0.863 | None | gnomAD-3.1.2 | 6.90317E-04 | None | None | None | None | N | None | 1.20656E-04 | 7.2065E-04 | 0 | 0 | 0 | None | 9.41E-05 | 0 | 1.27964E-03 | 0 | 4.78011E-04 |
| L/P | rs56399205 |
-0.764 | 1.0 | D | 0.853 | 0.863 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| L/P | rs56399205 |
-0.764 | 1.0 | D | 0.853 | 0.863 | None | gnomAD-4.0.0 | 1.15904E-03 | None | None | None | None | N | None | 1.33301E-04 | 4.16764E-04 | None | 0 | 0 | None | 1.24977E-04 | 0 | 1.49033E-03 | 3.29446E-05 | 1.05661E-03 |
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 | 0.9026 | likely_pathogenic | 0.9006 | pathogenic | -1.092 | Destabilizing | 0.999 | D | 0.723 | prob.delet. | None | None | None | None | N |
| L/C | 0.9105 | likely_pathogenic | 0.9102 | pathogenic | -0.928 | Destabilizing | 1.0 | D | 0.785 | deleterious | None | None | None | None | N |
| L/D | 0.9993 | likely_pathogenic | 0.999 | pathogenic | -1.968 | Destabilizing | 1.0 | D | 0.856 | deleterious | None | None | None | None | N |
| L/E | 0.994 | likely_pathogenic | 0.993 | pathogenic | -1.772 | Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | N |
| L/F | 0.6173 | likely_pathogenic | 0.5942 | pathogenic | -0.807 | Destabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | N |
| L/G | 0.9844 | likely_pathogenic | 0.9812 | pathogenic | -1.434 | Destabilizing | 1.0 | D | 0.843 | deleterious | None | None | None | None | N |
| L/H | 0.9892 | likely_pathogenic | 0.9874 | pathogenic | -1.811 | Destabilizing | 1.0 | D | 0.813 | deleterious | None | None | None | None | N |
| L/I | 0.1854 | likely_benign | 0.1925 | benign | -0.07 | Destabilizing | 0.999 | D | 0.616 | neutral | None | None | None | None | N |
| L/K | 0.9886 | likely_pathogenic | 0.9863 | pathogenic | -1.061 | Destabilizing | 1.0 | D | 0.859 | deleterious | None | None | None | None | N |
| L/M | 0.2811 | likely_benign | 0.2767 | benign | -0.593 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | D | 0.558057316 | None | None | N |
| L/N | 0.9963 | likely_pathogenic | 0.9953 | pathogenic | -1.667 | Destabilizing | 1.0 | D | 0.856 | deleterious | None | None | None | None | N |
| L/P | 0.9906 | likely_pathogenic | 0.9891 | pathogenic | -0.405 | Destabilizing | 1.0 | D | 0.853 | deleterious | D | 0.638900617 | None | None | N |
| L/Q | 0.978 | likely_pathogenic | 0.9744 | pathogenic | -1.261 | Destabilizing | 1.0 | D | 0.857 | deleterious | D | 0.638900617 | None | None | N |
| L/R | 0.9782 | likely_pathogenic | 0.9749 | pathogenic | -1.583 | Destabilizing | 1.0 | D | 0.848 | deleterious | D | 0.638900617 | None | None | N |
| L/S | 0.992 | likely_pathogenic | 0.9915 | pathogenic | -1.774 | Destabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | None | N |
| L/T | 0.9593 | likely_pathogenic | 0.9569 | pathogenic | -1.468 | Destabilizing | 1.0 | D | 0.8 | deleterious | None | None | None | None | N |
| L/V | 0.2661 | likely_benign | 0.2922 | benign | -0.405 | Destabilizing | 0.999 | D | 0.639 | neutral | D | 0.566152718 | None | None | N |
| L/W | 0.9467 | likely_pathogenic | 0.9432 | pathogenic | -1.108 | Destabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | N |
| L/Y | 0.9673 | likely_pathogenic | 0.9634 | pathogenic | -0.951 | Destabilizing | 1.0 | D | 0.787 | 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.