Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 13729 | 41410;41411;41412 | chr2:178636542;178636541;178636540 | chr2:179501269;179501268;179501267 |
| N2AB | 12088 | 36487;36488;36489 | chr2:178636542;178636541;178636540 | chr2:179501269;179501268;179501267 |
| N2A | 11161 | 33706;33707;33708 | chr2:178636542;178636541;178636540 | chr2:179501269;179501268;179501267 |
| N2B | 4664 | 14215;14216;14217 | chr2:178636542;178636541;178636540 | chr2:179501269;179501268;179501267 |
| Novex-1 | 4789 | 14590;14591;14592 | chr2:178636542;178636541;178636540 | chr2:179501269;179501268;179501267 |
| Novex-2 | 4856 | 14791;14792;14793 | chr2:178636542;178636541;178636540 | chr2:179501269;179501268;179501267 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/G | rs1372970593  |
-0.764 | 0.999 | N | 0.461 | 0.191 | 0.188950314367 | 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 |
| S/G | rs1372970593 |
-0.764 | 0.999 | N | 0.461 | 0.191 | 0.188950314367 | gnomAD-4.0.0 | 4.10599E-06 | None | None | None | None | N | None | 0 | 2.23654E-05 | None | 0 | 0 | None | 0 | 0 | 4.49801E-06 | 0 | 0 |
| S/R | rs1303644206 |
-0.448 | 1.0 | N | 0.629 | 0.525 | 0.293502639404 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.4239 | ambiguous | 0.5399 | ambiguous | -0.451 | Destabilizing | 0.998 | D | 0.423 | neutral | None | None | None | None | N |
| S/C | 0.6831 | likely_pathogenic | 0.7531 | pathogenic | -0.274 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | D | 0.572802814 | None | None | N |
| S/D | 0.8212 | likely_pathogenic | 0.9299 | pathogenic | 0.156 | Stabilizing | 0.999 | D | 0.566 | neutral | None | None | None | None | N |
| S/E | 0.9724 | likely_pathogenic | 0.9866 | pathogenic | 0.134 | Stabilizing | 0.999 | D | 0.553 | neutral | None | None | None | None | N |
| S/F | 0.8771 | likely_pathogenic | 0.9416 | pathogenic | -0.739 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | N |
| S/G | 0.1811 | likely_benign | 0.249 | benign | -0.665 | Destabilizing | 0.999 | D | 0.461 | neutral | N | 0.454264288 | None | None | N |
| S/H | 0.8596 | likely_pathogenic | 0.923 | pathogenic | -1.064 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | N |
| S/I | 0.8796 | likely_pathogenic | 0.9342 | pathogenic | -0.001 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | D | 0.560750442 | None | None | N |
| S/K | 0.9915 | likely_pathogenic | 0.9959 | pathogenic | -0.557 | Destabilizing | 0.999 | D | 0.557 | neutral | None | None | None | None | N |
| S/L | 0.625 | likely_pathogenic | 0.7645 | pathogenic | -0.001 | Destabilizing | 1.0 | D | 0.629 | neutral | None | None | None | None | N |
| S/M | 0.7611 | likely_pathogenic | 0.8497 | pathogenic | 0.039 | Stabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | N |
| S/N | 0.4995 | ambiguous | 0.6688 | pathogenic | -0.423 | Destabilizing | 0.999 | D | 0.549 | neutral | N | 0.457358743 | None | None | N |
| S/P | 0.9892 | likely_pathogenic | 0.9951 | pathogenic | -0.118 | Destabilizing | 1.0 | D | 0.631 | neutral | None | None | None | None | N |
| S/Q | 0.9633 | likely_pathogenic | 0.9795 | pathogenic | -0.511 | Destabilizing | 1.0 | D | 0.653 | neutral | None | None | None | None | N |
| S/R | 0.9913 | likely_pathogenic | 0.9954 | pathogenic | -0.439 | Destabilizing | 1.0 | D | 0.629 | neutral | N | 0.508940507 | None | None | N |
| S/T | 0.2883 | likely_benign | 0.414 | ambiguous | -0.441 | Destabilizing | 0.999 | D | 0.446 | neutral | N | 0.449617948 | None | None | N |
| S/V | 0.8747 | likely_pathogenic | 0.9364 | pathogenic | -0.118 | Destabilizing | 1.0 | D | 0.675 | neutral | None | None | None | None | N |
| S/W | 0.947 | likely_pathogenic | 0.9735 | pathogenic | -0.803 | Destabilizing | 1.0 | D | 0.759 | deleterious | None | None | None | None | N |
| S/Y | 0.848 | likely_pathogenic | 0.9236 | pathogenic | -0.511 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | 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.