Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35626 | 107101;107102;107103 | chr2:178528875;178528874;178528873 | chr2:179393602;179393601;179393600 |
| N2AB | 33985 | 102178;102179;102180 | chr2:178528875;178528874;178528873 | chr2:179393602;179393601;179393600 |
| N2A | 33058 | 99397;99398;99399 | chr2:178528875;178528874;178528873 | chr2:179393602;179393601;179393600 |
| N2B | 26561 | 79906;79907;79908 | chr2:178528875;178528874;178528873 | chr2:179393602;179393601;179393600 |
| Novex-1 | 26686 | 80281;80282;80283 | chr2:178528875;178528874;178528873 | chr2:179393602;179393601;179393600 |
| Novex-2 | 26753 | 80482;80483;80484 | chr2:178528875;178528874;178528873 | chr2:179393602;179393601;179393600 |
| 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/V | rs373152640  |
-1.401 | 0.999 | N | 0.604 | 0.457 | None | gnomAD-2.1.1 | 4.64E-05 | None | None | None | None | N | None | 3.71962E-04 | 0 | None | 0 | 5.12E-05 | None | 3.27E-05 | None | 0 | 7.8E-06 | 1.40331E-04 |
| L/V | rs373152640 |
-1.401 | 0.999 | N | 0.604 | 0.457 | None | gnomAD-3.1.2 | 6.57E-05 | None | None | None | None | N | None | 1.68878E-04 | 0 | 0 | 0 | 1.92234E-04 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| L/V | rs373152640 |
-1.401 | 0.999 | N | 0.604 | 0.457 | None | 1000 genomes | 5.99042E-04 | None | None | None | None | N | None | 1.5E-03 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| L/V | rs373152640 |
-1.401 | 0.999 | N | 0.604 | 0.457 | None | gnomAD-4.0.0 | 4.39903E-05 | None | None | None | None | N | None | 5.46288E-04 | 0 | None | 0 | 1.78213E-04 | None | 0 | 1.64962E-04 | 4.2377E-06 | 3.29366E-05 | 2.08053E-04 |
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 | 0.8638 | likely_pathogenic | 0.8781 | pathogenic | -2.4 | Highly Destabilizing | 0.999 | D | 0.766 | deleterious | None | None | None | None | N |
| L/C | 0.8988 | likely_pathogenic | 0.9203 | pathogenic | -1.739 | Destabilizing | 1.0 | D | 0.867 | deleterious | None | None | None | None | N |
| L/D | 0.997 | likely_pathogenic | 0.9975 | pathogenic | -2.8 | Highly Destabilizing | 1.0 | D | 0.923 | deleterious | None | None | None | None | N |
| L/E | 0.9799 | likely_pathogenic | 0.9832 | pathogenic | -2.528 | Highly Destabilizing | 1.0 | D | 0.907 | deleterious | None | None | None | None | N |
| L/F | 0.296 | likely_benign | 0.3385 | benign | -1.55 | Destabilizing | 1.0 | D | 0.8 | deleterious | N | 0.484054876 | None | None | N |
| L/G | 0.9697 | likely_pathogenic | 0.9738 | pathogenic | -2.933 | Highly Destabilizing | 1.0 | D | 0.902 | deleterious | None | None | None | None | N |
| L/H | 0.9426 | likely_pathogenic | 0.9565 | pathogenic | -2.403 | Highly Destabilizing | 1.0 | D | 0.893 | deleterious | None | None | None | None | N |
| L/I | 0.1748 | likely_benign | 0.1766 | benign | -0.826 | Destabilizing | 0.999 | D | 0.582 | neutral | N | 0.51189171 | None | None | N |
| L/K | 0.9563 | likely_pathogenic | 0.9632 | pathogenic | -1.886 | Destabilizing | 1.0 | D | 0.913 | deleterious | None | None | None | None | N |
| L/M | 0.2492 | likely_benign | 0.258 | benign | -0.862 | Destabilizing | 1.0 | D | 0.75 | deleterious | None | None | None | None | N |
| L/N | 0.9862 | likely_pathogenic | 0.9886 | pathogenic | -2.411 | Highly Destabilizing | 1.0 | D | 0.923 | deleterious | None | None | None | None | N |
| L/P | 0.9837 | likely_pathogenic | 0.9859 | pathogenic | -1.338 | Destabilizing | 1.0 | D | 0.922 | deleterious | None | None | None | None | N |
| L/Q | 0.9025 | likely_pathogenic | 0.9196 | pathogenic | -2.152 | Highly Destabilizing | 1.0 | D | 0.929 | deleterious | None | None | None | None | N |
| L/R | 0.9294 | likely_pathogenic | 0.9406 | pathogenic | -1.877 | Destabilizing | 1.0 | D | 0.922 | deleterious | None | None | None | None | N |
| L/S | 0.9637 | likely_pathogenic | 0.9718 | pathogenic | -3.037 | Highly Destabilizing | 1.0 | D | 0.916 | deleterious | N | 0.513113266 | None | None | N |
| L/T | 0.9133 | likely_pathogenic | 0.928 | pathogenic | -2.6 | Highly Destabilizing | 1.0 | D | 0.861 | deleterious | None | None | None | None | N |
| L/V | 0.2285 | likely_benign | 0.2341 | benign | -1.338 | Destabilizing | 0.999 | D | 0.604 | neutral | N | 0.512502488 | None | None | N |
| L/W | 0.777 | likely_pathogenic | 0.8196 | pathogenic | -1.834 | Destabilizing | 1.0 | D | 0.886 | deleterious | None | None | None | None | N |
| L/Y | 0.8792 | likely_pathogenic | 0.9021 | pathogenic | -1.563 | Destabilizing | 1.0 | D | 0.871 | 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.