Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26897 | 80914;80915;80916 | chr2:178565443;178565442;178565441 | chr2:179430170;179430169;179430168 |
| N2AB | 25256 | 75991;75992;75993 | chr2:178565443;178565442;178565441 | chr2:179430170;179430169;179430168 |
| N2A | 24329 | 73210;73211;73212 | chr2:178565443;178565442;178565441 | chr2:179430170;179430169;179430168 |
| N2B | 17832 | 53719;53720;53721 | chr2:178565443;178565442;178565441 | chr2:179430170;179430169;179430168 |
| Novex-1 | 17957 | 54094;54095;54096 | chr2:178565443;178565442;178565441 | chr2:179430170;179430169;179430168 |
| Novex-2 | 18024 | 54295;54296;54297 | chr2:178565443;178565442;178565441 | chr2:179430170;179430169;179430168 |
| 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 | rs754480353  |
-1.36 | 1.0 | N | 0.821 | 0.597 | None | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| L/P | rs754480353 |
-1.36 | 1.0 | N | 0.821 | 0.597 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| L/P | rs754480353 |
-1.36 | 1.0 | N | 0.821 | 0.597 | None | gnomAD-4.0.0 | 7.69039E-06 | None | None | None | None | N | None | 0 | 8.48234E-05 | None | 0 | 0 | None | 0 | 0 | 2.39383E-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 | 0.6281 | likely_pathogenic | 0.6877 | pathogenic | -2.069 | Highly Destabilizing | 0.999 | D | 0.731 | prob.delet. | None | None | None | None | N |
| L/C | 0.577 | likely_pathogenic | 0.6321 | pathogenic | -1.444 | Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | N |
| L/D | 0.9868 | likely_pathogenic | 0.9912 | pathogenic | -1.572 | Destabilizing | 1.0 | D | 0.825 | deleterious | None | None | None | None | N |
| L/E | 0.9262 | likely_pathogenic | 0.9489 | pathogenic | -1.414 | Destabilizing | 1.0 | D | 0.814 | deleterious | None | None | None | None | N |
| L/F | 0.2534 | likely_benign | 0.2795 | benign | -1.158 | Destabilizing | 1.0 | D | 0.765 | deleterious | N | 0.506850725 | None | None | N |
| L/G | 0.8896 | likely_pathogenic | 0.9192 | pathogenic | -2.553 | Highly Destabilizing | 1.0 | D | 0.813 | deleterious | None | None | None | None | N |
| L/H | 0.7596 | likely_pathogenic | 0.8274 | pathogenic | -1.769 | Destabilizing | 1.0 | D | 0.802 | deleterious | N | 0.508958603 | None | None | N |
| L/I | 0.1114 | likely_benign | 0.1148 | benign | -0.728 | Destabilizing | 0.999 | D | 0.567 | neutral | N | 0.467137544 | None | None | N |
| L/K | 0.8274 | likely_pathogenic | 0.8826 | pathogenic | -1.553 | Destabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | N |
| L/M | 0.1287 | likely_benign | 0.1442 | benign | -0.699 | Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | N |
| L/N | 0.9217 | likely_pathogenic | 0.9484 | pathogenic | -1.674 | Destabilizing | 1.0 | D | 0.825 | deleterious | None | None | None | None | N |
| L/P | 0.9878 | likely_pathogenic | 0.9894 | pathogenic | -1.149 | Destabilizing | 1.0 | D | 0.821 | deleterious | N | 0.520314909 | None | None | N |
| L/Q | 0.6525 | likely_pathogenic | 0.7315 | pathogenic | -1.607 | Destabilizing | 1.0 | D | 0.816 | deleterious | None | None | None | None | N |
| L/R | 0.7347 | likely_pathogenic | 0.7986 | pathogenic | -1.204 | Destabilizing | 1.0 | D | 0.811 | deleterious | N | 0.508705114 | None | None | N |
| L/S | 0.8403 | likely_pathogenic | 0.8811 | pathogenic | -2.432 | Highly Destabilizing | 1.0 | D | 0.8 | deleterious | None | None | None | None | N |
| L/T | 0.6243 | likely_pathogenic | 0.6922 | pathogenic | -2.123 | Highly Destabilizing | 1.0 | D | 0.813 | deleterious | None | None | None | None | N |
| L/V | 0.1274 | likely_benign | 0.1301 | benign | -1.149 | Destabilizing | 0.999 | D | 0.553 | neutral | N | 0.45622433 | None | None | N |
| L/W | 0.6314 | likely_pathogenic | 0.6825 | pathogenic | -1.37 | Destabilizing | 1.0 | D | 0.738 | prob.delet. | None | None | None | None | N |
| L/Y | 0.6961 | likely_pathogenic | 0.772 | pathogenic | -1.102 | Destabilizing | 1.0 | D | 0.828 | 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.