Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23319 | 70180;70181;70182 | chr2:178576177;178576176;178576175 | chr2:179440904;179440903;179440902 |
| N2AB | 21678 | 65257;65258;65259 | chr2:178576177;178576176;178576175 | chr2:179440904;179440903;179440902 |
| N2A | 20751 | 62476;62477;62478 | chr2:178576177;178576176;178576175 | chr2:179440904;179440903;179440902 |
| N2B | 14254 | 42985;42986;42987 | chr2:178576177;178576176;178576175 | chr2:179440904;179440903;179440902 |
| Novex-1 | 14379 | 43360;43361;43362 | chr2:178576177;178576176;178576175 | chr2:179440904;179440903;179440902 |
| Novex-2 | 14446 | 43561;43562;43563 | chr2:178576177;178576176;178576175 | chr2:179440904;179440903;179440902 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/M | rs540840413  |
-1.1 | 0.003 | N | 0.201 | 0.058 | 0.323886383625 | gnomAD-2.1.1 | 5.73E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 4.26313E-04 | None | 0 | 2.35E-05 | 0 |
| I/M | rs540840413 |
-1.1 | 0.003 | N | 0.201 | 0.058 | 0.323886383625 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 8.29531E-04 | 0 |
| I/M | rs540840413 |
-1.1 | 0.003 | N | 0.201 | 0.058 | 0.323886383625 | 1000 genomes | 3.99361E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 2E-03 | None |
| I/M | rs540840413 |
-1.1 | 0.003 | N | 0.201 | 0.058 | 0.323886383625 | gnomAD-4.0.0 | 3.03769E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.6309E-06 | 4.17693E-04 | 3.20277E-05 |
| I/V | rs753718401 |
-1.233 | None | N | 0.145 | 0.071 | 0.139678290688 | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| I/V | rs753718401 |
-1.233 | None | N | 0.145 | 0.071 | 0.139678290688 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 6.07533E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.3378 | likely_benign | 0.3517 | ambiguous | -2.131 | Highly Destabilizing | 0.055 | N | 0.416 | neutral | None | None | None | None | I |
| I/C | 0.5205 | ambiguous | 0.5263 | ambiguous | -1.819 | Destabilizing | 0.883 | D | 0.549 | neutral | None | None | None | None | I |
| I/D | 0.8342 | likely_pathogenic | 0.8432 | pathogenic | -1.812 | Destabilizing | 0.667 | D | 0.619 | neutral | None | None | None | None | I |
| I/E | 0.543 | ambiguous | 0.5774 | pathogenic | -1.717 | Destabilizing | 0.667 | D | 0.619 | neutral | None | None | None | None | I |
| I/F | 0.1635 | likely_benign | 0.1483 | benign | -1.456 | Destabilizing | 0.175 | N | 0.545 | neutral | N | 0.48384894 | None | None | I |
| I/G | 0.6964 | likely_pathogenic | 0.7084 | pathogenic | -2.532 | Highly Destabilizing | 0.364 | N | 0.615 | neutral | None | None | None | None | I |
| I/H | 0.5542 | ambiguous | 0.5742 | pathogenic | -1.71 | Destabilizing | 0.958 | D | 0.607 | neutral | None | None | None | None | I |
| I/K | 0.3355 | likely_benign | 0.3811 | ambiguous | -1.4 | Destabilizing | 0.22 | N | 0.617 | neutral | None | None | None | None | I |
| I/L | 0.0857 | likely_benign | 0.091 | benign | -1.046 | Destabilizing | None | N | 0.153 | neutral | N | 0.429686381 | None | None | I |
| I/M | 0.0757 | likely_benign | 0.0765 | benign | -1.123 | Destabilizing | 0.003 | N | 0.201 | neutral | N | 0.4550089 | None | None | I |
| I/N | 0.4741 | ambiguous | 0.5018 | ambiguous | -1.436 | Destabilizing | 0.602 | D | 0.609 | neutral | N | 0.489390833 | None | None | I |
| I/P | 0.9764 | likely_pathogenic | 0.9773 | pathogenic | -1.382 | Destabilizing | 0.859 | D | 0.617 | neutral | None | None | None | None | I |
| I/Q | 0.3814 | ambiguous | 0.4089 | ambiguous | -1.536 | Destabilizing | 0.497 | N | 0.607 | neutral | None | None | None | None | I |
| I/R | 0.2953 | likely_benign | 0.3327 | benign | -0.937 | Destabilizing | 0.497 | N | 0.615 | neutral | None | None | None | None | I |
| I/S | 0.3724 | ambiguous | 0.3928 | ambiguous | -2.191 | Highly Destabilizing | 0.175 | N | 0.567 | neutral | N | 0.484022298 | None | None | I |
| I/T | 0.2301 | likely_benign | 0.2504 | benign | -1.968 | Destabilizing | 0.175 | N | 0.527 | neutral | N | 0.445599983 | None | None | I |
| I/V | 0.059 | likely_benign | 0.0595 | benign | -1.382 | Destabilizing | None | N | 0.145 | neutral | N | 0.337386722 | None | None | I |
| I/W | 0.7287 | likely_pathogenic | 0.7179 | pathogenic | -1.562 | Destabilizing | 0.958 | D | 0.631 | neutral | None | None | None | None | I |
| I/Y | 0.5218 | ambiguous | 0.504 | ambiguous | -1.31 | Destabilizing | 0.667 | D | 0.599 | neutral | None | None | None | None | I |
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.