Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33731 | 101416;101417;101418 | chr2:178535424;178535423;178535422 | chr2:179400151;179400150;179400149 |
| N2AB | 32090 | 96493;96494;96495 | chr2:178535424;178535423;178535422 | chr2:179400151;179400150;179400149 |
| N2A | 31163 | 93712;93713;93714 | chr2:178535424;178535423;178535422 | chr2:179400151;179400150;179400149 |
| N2B | 24666 | 74221;74222;74223 | chr2:178535424;178535423;178535422 | chr2:179400151;179400150;179400149 |
| Novex-1 | 24791 | 74596;74597;74598 | chr2:178535424;178535423;178535422 | chr2:179400151;179400150;179400149 |
| Novex-2 | 24858 | 74797;74798;74799 | chr2:178535424;178535423;178535422 | chr2:179400151;179400150;179400149 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | rs746383312  |
-0.888 | 0.963 | N | 0.501 | 0.29 | 0.162503812791 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.87E-06 | 0 |
| T/A | rs746383312 |
-0.888 | 0.963 | N | 0.501 | 0.29 | 0.162503812791 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1218 | likely_benign | 0.1023 | benign | -0.652 | Destabilizing | 0.963 | D | 0.501 | neutral | N | 0.430091813 | None | None | N |
| T/C | 0.7565 | likely_pathogenic | 0.6875 | pathogenic | -0.317 | Destabilizing | 1.0 | D | 0.623 | neutral | None | None | None | None | N |
| T/D | 0.7169 | likely_pathogenic | 0.608 | pathogenic | -0.029 | Destabilizing | 0.999 | D | 0.584 | neutral | None | None | None | None | N |
| T/E | 0.5941 | likely_pathogenic | 0.4877 | ambiguous | -0.088 | Destabilizing | 1.0 | D | 0.583 | neutral | None | None | None | None | N |
| T/F | 0.7144 | likely_pathogenic | 0.6046 | pathogenic | -0.986 | Destabilizing | 1.0 | D | 0.696 | prob.neutral | None | None | None | None | N |
| T/G | 0.4161 | ambiguous | 0.3509 | ambiguous | -0.829 | Destabilizing | 1.0 | D | 0.629 | neutral | None | None | None | None | N |
| T/H | 0.6807 | likely_pathogenic | 0.5709 | pathogenic | -1.142 | Destabilizing | 1.0 | D | 0.677 | prob.neutral | None | None | None | None | N |
| T/I | 0.3933 | ambiguous | 0.2938 | benign | -0.291 | Destabilizing | 1.0 | D | 0.634 | neutral | N | 0.474498738 | None | None | N |
| T/K | 0.4855 | ambiguous | 0.3941 | ambiguous | -0.593 | Destabilizing | 1.0 | D | 0.586 | neutral | None | None | None | None | N |
| T/L | 0.219 | likely_benign | 0.1691 | benign | -0.291 | Destabilizing | 0.999 | D | 0.553 | neutral | None | None | None | None | N |
| T/M | 0.2014 | likely_benign | 0.1581 | benign | 0.05 | Stabilizing | 1.0 | D | 0.625 | neutral | None | None | None | None | N |
| T/N | 0.3074 | likely_benign | 0.2308 | benign | -0.356 | Destabilizing | 0.999 | D | 0.661 | neutral | N | 0.453027388 | None | None | N |
| T/P | 0.2242 | likely_benign | 0.1769 | benign | -0.381 | Destabilizing | 0.202 | N | 0.35 | neutral | N | 0.454470183 | None | None | N |
| T/Q | 0.4818 | ambiguous | 0.3926 | ambiguous | -0.615 | Destabilizing | 1.0 | D | 0.648 | neutral | None | None | None | None | N |
| T/R | 0.4925 | ambiguous | 0.3858 | ambiguous | -0.279 | Destabilizing | 1.0 | D | 0.633 | neutral | None | None | None | None | N |
| T/S | 0.2135 | likely_benign | 0.1745 | benign | -0.608 | Destabilizing | 0.982 | D | 0.521 | neutral | N | 0.435113631 | None | None | N |
| T/V | 0.2292 | likely_benign | 0.192 | benign | -0.381 | Destabilizing | 0.999 | D | 0.562 | neutral | None | None | None | None | N |
| T/W | 0.9377 | likely_pathogenic | 0.9011 | pathogenic | -0.923 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | N |
| T/Y | 0.7785 | likely_pathogenic | 0.6663 | pathogenic | -0.688 | Destabilizing | 1.0 | D | 0.692 | prob.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.