Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17952 | 54079;54080;54081 | chr2:178605441;178605440;178605439 | chr2:179470168;179470167;179470166 |
| N2AB | 16311 | 49156;49157;49158 | chr2:178605441;178605440;178605439 | chr2:179470168;179470167;179470166 |
| N2A | 15384 | 46375;46376;46377 | chr2:178605441;178605440;178605439 | chr2:179470168;179470167;179470166 |
| N2B | 8887 | 26884;26885;26886 | chr2:178605441;178605440;178605439 | chr2:179470168;179470167;179470166 |
| Novex-1 | 9012 | 27259;27260;27261 | chr2:178605441;178605440;178605439 | chr2:179470168;179470167;179470166 |
| Novex-2 | 9079 | 27460;27461;27462 | chr2:178605441;178605440;178605439 | chr2:179470168;179470167;179470166 |
| 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/I | None | None | 0.666 | N | 0.536 | 0.055 | 0.236890367714 | gnomAD-4.0.0 | 1.60772E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.88944E-06 | 0 | 0 |
| L/R | rs1419642739  |
-1.19 | 0.966 | N | 0.709 | 0.408 | 0.639332231701 | gnomAD-2.1.1 | 4.08E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.02E-06 | 0 |
| L/R | rs1419642739 |
-1.19 | 0.966 | N | 0.709 | 0.408 | 0.639332231701 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| L/R | rs1419642739 |
-1.19 | 0.966 | N | 0.709 | 0.408 | 0.639332231701 | gnomAD-4.0.0 | 1.31605E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.94421E-05 | 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 | 0.7862 | likely_pathogenic | 0.6958 | pathogenic | -2.315 | Highly Destabilizing | 0.841 | D | 0.55 | neutral | None | None | None | None | N |
| L/C | 0.8271 | likely_pathogenic | 0.7729 | pathogenic | -1.552 | Destabilizing | 0.998 | D | 0.566 | neutral | None | None | None | None | N |
| L/D | 0.9894 | likely_pathogenic | 0.9821 | pathogenic | -2.443 | Highly Destabilizing | 0.991 | D | 0.799 | deleterious | None | None | None | None | N |
| L/E | 0.9173 | likely_pathogenic | 0.8678 | pathogenic | -2.241 | Highly Destabilizing | 0.991 | D | 0.783 | deleterious | None | None | None | None | N |
| L/F | 0.6233 | likely_pathogenic | 0.4956 | ambiguous | -1.386 | Destabilizing | 0.028 | N | 0.375 | neutral | N | 0.466440806 | None | None | N |
| L/G | 0.9579 | likely_pathogenic | 0.929 | pathogenic | -2.835 | Highly Destabilizing | 0.974 | D | 0.763 | deleterious | None | None | None | None | N |
| L/H | 0.8914 | likely_pathogenic | 0.8171 | pathogenic | -2.183 | Highly Destabilizing | 0.997 | D | 0.793 | deleterious | N | 0.467201275 | None | None | N |
| L/I | 0.1681 | likely_benign | 0.1539 | benign | -0.834 | Destabilizing | 0.666 | D | 0.536 | neutral | N | 0.446538559 | None | None | N |
| L/K | 0.8758 | likely_pathogenic | 0.8152 | pathogenic | -1.863 | Destabilizing | 0.974 | D | 0.683 | prob.neutral | None | None | None | None | N |
| L/M | 0.2285 | likely_benign | 0.1868 | benign | -0.702 | Destabilizing | 0.522 | D | 0.419 | neutral | None | None | None | None | N |
| L/N | 0.9364 | likely_pathogenic | 0.9011 | pathogenic | -2.137 | Highly Destabilizing | 0.991 | D | 0.797 | deleterious | None | None | None | None | N |
| L/P | 0.9817 | likely_pathogenic | 0.9726 | pathogenic | -1.306 | Destabilizing | 0.989 | D | 0.794 | deleterious | N | 0.510571395 | None | None | N |
| L/Q | 0.7424 | likely_pathogenic | 0.6256 | pathogenic | -2.036 | Highly Destabilizing | 0.974 | D | 0.707 | prob.delet. | None | None | None | None | N |
| L/R | 0.8304 | likely_pathogenic | 0.757 | pathogenic | -1.521 | Destabilizing | 0.966 | D | 0.709 | prob.delet. | N | 0.509877961 | None | None | N |
| L/S | 0.9117 | likely_pathogenic | 0.8446 | pathogenic | -2.823 | Highly Destabilizing | 0.974 | D | 0.638 | neutral | None | None | None | None | N |
| L/T | 0.7347 | likely_pathogenic | 0.6471 | pathogenic | -2.473 | Highly Destabilizing | 0.949 | D | 0.587 | neutral | None | None | None | None | N |
| L/V | 0.1896 | likely_benign | 0.1606 | benign | -1.306 | Destabilizing | 0.051 | N | 0.39 | neutral | N | 0.415540861 | None | None | N |
| L/W | 0.8676 | likely_pathogenic | 0.7979 | pathogenic | -1.731 | Destabilizing | 0.998 | D | 0.718 | prob.delet. | None | None | None | None | N |
| L/Y | 0.8983 | likely_pathogenic | 0.8328 | pathogenic | -1.417 | Destabilizing | 0.903 | D | 0.572 | 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.