Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33136 | 99631;99632;99633 | chr2:178537801;178537800;178537799 | chr2:179402528;179402527;179402526 |
| N2AB | 31495 | 94708;94709;94710 | chr2:178537801;178537800;178537799 | chr2:179402528;179402527;179402526 |
| N2A | 30568 | 91927;91928;91929 | chr2:178537801;178537800;178537799 | chr2:179402528;179402527;179402526 |
| N2B | 24071 | 72436;72437;72438 | chr2:178537801;178537800;178537799 | chr2:179402528;179402527;179402526 |
| Novex-1 | 24196 | 72811;72812;72813 | chr2:178537801;178537800;178537799 | chr2:179402528;179402527;179402526 |
| Novex-2 | 24263 | 73012;73013;73014 | chr2:178537801;178537800;178537799 | chr2:179402528;179402527;179402526 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/G | rs746964527  |
-2.556 | 1.0 | N | 0.742 | 0.472 | 0.237489013734 | gnomAD-2.1.1 | 2.01E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 4.43E-05 | 0 |
| R/G | rs746964527 |
-2.556 | 1.0 | N | 0.742 | 0.472 | 0.237489013734 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/G | rs746964527 |
-2.556 | 1.0 | N | 0.742 | 0.472 | 0.237489013734 | gnomAD-4.0.0 | 6.19709E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.62854E-06 | 0 | 1.60113E-05 |
| R/K | None | None | 0.997 | N | 0.555 | 0.297 | 0.151104730317 | gnomAD-4.0.0 | 3.18288E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.71706E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9577 | likely_pathogenic | 0.9451 | pathogenic | -2.122 | Highly Destabilizing | 1.0 | D | 0.583 | neutral | None | None | None | None | N |
| R/C | 0.4549 | ambiguous | 0.3948 | ambiguous | -1.955 | Destabilizing | 1.0 | D | 0.853 | deleterious | None | None | None | None | N |
| R/D | 0.9913 | likely_pathogenic | 0.9894 | pathogenic | -0.921 | Destabilizing | 1.0 | D | 0.784 | deleterious | None | None | None | None | N |
| R/E | 0.9534 | likely_pathogenic | 0.9423 | pathogenic | -0.679 | Destabilizing | 1.0 | D | 0.603 | neutral | None | None | None | None | N |
| R/F | 0.9405 | likely_pathogenic | 0.938 | pathogenic | -1.4 | Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | N |
| R/G | 0.9355 | likely_pathogenic | 0.9106 | pathogenic | -2.498 | Highly Destabilizing | 1.0 | D | 0.742 | deleterious | N | 0.468697942 | None | None | N |
| R/H | 0.2562 | likely_benign | 0.2305 | benign | -2.046 | Highly Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | N |
| R/I | 0.8754 | likely_pathogenic | 0.851 | pathogenic | -1.024 | Destabilizing | 1.0 | D | 0.832 | deleterious | N | 0.46554439 | None | None | N |
| R/K | 0.3419 | ambiguous | 0.3377 | benign | -1.05 | Destabilizing | 0.997 | D | 0.555 | neutral | N | 0.365004893 | None | None | N |
| R/L | 0.7763 | likely_pathogenic | 0.7508 | pathogenic | -1.024 | Destabilizing | 1.0 | D | 0.742 | deleterious | None | None | None | None | N |
| R/M | 0.9205 | likely_pathogenic | 0.8936 | pathogenic | -1.417 | Destabilizing | 1.0 | D | 0.808 | deleterious | None | None | None | None | N |
| R/N | 0.9685 | likely_pathogenic | 0.9635 | pathogenic | -1.363 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | N |
| R/P | 0.9968 | likely_pathogenic | 0.995 | pathogenic | -1.38 | Destabilizing | 1.0 | D | 0.796 | deleterious | None | None | None | None | N |
| R/Q | 0.3786 | ambiguous | 0.3472 | ambiguous | -1.272 | Destabilizing | 1.0 | D | 0.675 | neutral | None | None | None | None | N |
| R/S | 0.9606 | likely_pathogenic | 0.9505 | pathogenic | -2.404 | Highly Destabilizing | 1.0 | D | 0.73 | prob.delet. | N | 0.459556909 | None | None | N |
| R/T | 0.9538 | likely_pathogenic | 0.9364 | pathogenic | -1.916 | Destabilizing | 1.0 | D | 0.72 | prob.delet. | N | 0.461038166 | None | None | N |
| R/V | 0.9116 | likely_pathogenic | 0.8992 | pathogenic | -1.38 | Destabilizing | 1.0 | D | 0.807 | deleterious | None | None | None | None | N |
| R/W | 0.6704 | likely_pathogenic | 0.619 | pathogenic | -0.804 | Destabilizing | 1.0 | D | 0.849 | deleterious | None | None | None | None | N |
| R/Y | 0.8139 | likely_pathogenic | 0.7944 | pathogenic | -0.732 | Destabilizing | 1.0 | D | 0.831 | 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.