Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15092 | 45499;45500;45501 | chr2:178621550;178621549;178621548 | chr2:179486277;179486276;179486275 |
| N2AB | 13451 | 40576;40577;40578 | chr2:178621550;178621549;178621548 | chr2:179486277;179486276;179486275 |
| N2A | 12524 | 37795;37796;37797 | chr2:178621550;178621549;178621548 | chr2:179486277;179486276;179486275 |
| N2B | 6027 | 18304;18305;18306 | chr2:178621550;178621549;178621548 | chr2:179486277;179486276;179486275 |
| Novex-1 | 6152 | 18679;18680;18681 | chr2:178621550;178621549;178621548 | chr2:179486277;179486276;179486275 |
| Novex-2 | 6219 | 18880;18881;18882 | chr2:178621550;178621549;178621548 | chr2:179486277;179486276;179486275 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/S | None | None | 0.549 | D | 0.553 | 0.308 | 0.497679007273 | gnomAD-4.0.0 | 6.8469E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99931E-07 | 0 | 0 |
| A/T | rs760392307  |
-1.654 | 0.729 | N | 0.561 | 0.283 | None | gnomAD-2.1.1 | 3.63E-05 | None | None | None | None | N | None | 0 | 5.82E-05 | None | 0 | 0 | None | 3.27E-05 | None | 4.64E-05 | 3.57E-05 | 1.66445E-04 |
| A/T | rs760392307 |
-1.654 | 0.729 | N | 0.561 | 0.283 | None | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 2.88184E-04 | 0 | None | 0 | 0 | 4.42E-05 | 0 | 0 |
| A/T | rs760392307 |
-1.654 | 0.729 | N | 0.561 | 0.283 | None | gnomAD-4.0.0 | 1.61254E-05 | None | None | None | None | N | None | 0 | 1.67196E-05 | None | 3.38295E-05 | 0 | None | 1.56245E-05 | 0 | 1.52659E-05 | 1.09815E-05 | 6.41169E-05 |
| A/V | None | None | 0.001 | N | 0.249 | 0.147 | 0.408036853922 | gnomAD-4.0.0 | 1.59387E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.78412E-05 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.5533 | ambiguous | 0.6357 | pathogenic | -1.882 | Destabilizing | 0.944 | D | 0.615 | neutral | None | None | None | None | N |
| A/D | 0.9565 | likely_pathogenic | 0.9708 | pathogenic | -3.292 | Highly Destabilizing | 0.773 | D | 0.689 | prob.neutral | D | 0.634531208 | None | None | N |
| A/E | 0.9432 | likely_pathogenic | 0.9602 | pathogenic | -3.173 | Highly Destabilizing | 0.818 | D | 0.659 | neutral | None | None | None | None | N |
| A/F | 0.8752 | likely_pathogenic | 0.9041 | pathogenic | -0.804 | Destabilizing | 0.69 | D | 0.683 | prob.neutral | None | None | None | None | N |
| A/G | 0.254 | likely_benign | 0.2994 | benign | -1.519 | Destabilizing | 0.492 | N | 0.565 | neutral | D | 0.673616931 | None | None | N |
| A/H | 0.9651 | likely_pathogenic | 0.9745 | pathogenic | -1.563 | Destabilizing | 0.981 | D | 0.659 | neutral | None | None | None | None | N |
| A/I | 0.4548 | ambiguous | 0.4894 | ambiguous | -0.275 | Destabilizing | 0.043 | N | 0.543 | neutral | None | None | None | None | N |
| A/K | 0.9742 | likely_pathogenic | 0.9842 | pathogenic | -1.493 | Destabilizing | 0.818 | D | 0.661 | neutral | None | None | None | None | N |
| A/L | 0.4818 | ambiguous | 0.5263 | ambiguous | -0.275 | Destabilizing | 0.001 | N | 0.375 | neutral | None | None | None | None | N |
| A/M | 0.617 | likely_pathogenic | 0.6263 | pathogenic | -0.655 | Destabilizing | 0.69 | D | 0.667 | neutral | None | None | None | None | N |
| A/N | 0.8685 | likely_pathogenic | 0.8952 | pathogenic | -1.901 | Destabilizing | 0.932 | D | 0.684 | prob.neutral | None | None | None | None | N |
| A/P | 0.6747 | likely_pathogenic | 0.7341 | pathogenic | -0.538 | Destabilizing | 0.963 | D | 0.685 | prob.neutral | D | 0.545972905 | None | None | N |
| A/Q | 0.927 | likely_pathogenic | 0.9452 | pathogenic | -1.87 | Destabilizing | 0.932 | D | 0.677 | prob.neutral | None | None | None | None | N |
| A/R | 0.9429 | likely_pathogenic | 0.9646 | pathogenic | -1.323 | Destabilizing | 0.818 | D | 0.692 | prob.neutral | None | None | None | None | N |
| A/S | 0.1708 | likely_benign | 0.184 | benign | -2.116 | Highly Destabilizing | 0.549 | D | 0.553 | neutral | D | 0.522868961 | None | None | N |
| A/T | 0.1514 | likely_benign | 0.1601 | benign | -1.908 | Destabilizing | 0.729 | D | 0.561 | neutral | N | 0.518363707 | None | None | N |
| A/V | 0.2105 | likely_benign | 0.2283 | benign | -0.538 | Destabilizing | 0.001 | N | 0.249 | neutral | N | 0.448788821 | None | None | N |
| A/W | 0.9862 | likely_pathogenic | 0.9925 | pathogenic | -1.447 | Destabilizing | 0.981 | D | 0.713 | prob.delet. | None | None | None | None | N |
| A/Y | 0.9538 | likely_pathogenic | 0.9688 | pathogenic | -1.027 | Destabilizing | 0.818 | D | 0.684 | 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.