Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24614 | 74065;74066;74067 | chr2:178572292;178572291;178572290 | chr2:179437019;179437018;179437017 |
| N2AB | 22973 | 69142;69143;69144 | chr2:178572292;178572291;178572290 | chr2:179437019;179437018;179437017 |
| N2A | 22046 | 66361;66362;66363 | chr2:178572292;178572291;178572290 | chr2:179437019;179437018;179437017 |
| N2B | 15549 | 46870;46871;46872 | chr2:178572292;178572291;178572290 | chr2:179437019;179437018;179437017 |
| Novex-1 | 15674 | 47245;47246;47247 | chr2:178572292;178572291;178572290 | chr2:179437019;179437018;179437017 |
| Novex-2 | 15741 | 47446;47447;47448 | chr2:178572292;178572291;178572290 | chr2:179437019;179437018;179437017 |
| 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/A | None | None | 0.99 | N | 0.472 | 0.157 | 0.236278675362 | gnomAD-4.0.0 | 2.05445E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 3.47987E-05 | 0 |
| S/P | rs759970555  |
0.199 | 1.0 | N | 0.695 | 0.312 | 0.297031009988 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| S/P | rs759970555 |
0.199 | 1.0 | N | 0.695 | 0.312 | 0.297031009988 | gnomAD-4.0.0 | 6.84817E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15996E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0731 | likely_benign | 0.0705 | benign | -0.445 | Destabilizing | 0.99 | D | 0.472 | neutral | N | 0.460929221 | None | None | N |
| S/C | 0.1665 | likely_benign | 0.1472 | benign | -0.371 | Destabilizing | 1.0 | D | 0.736 | deleterious | None | None | None | None | N |
| S/D | 0.9753 | likely_pathogenic | 0.9716 | pathogenic | -0.014 | Destabilizing | 0.999 | D | 0.695 | prob.delet. | None | None | None | None | N |
| S/E | 0.9664 | likely_pathogenic | 0.9615 | pathogenic | -0.11 | Destabilizing | 1.0 | D | 0.678 | prob.neutral | None | None | None | None | N |
| S/F | 0.7543 | likely_pathogenic | 0.6741 | pathogenic | -0.981 | Destabilizing | 1.0 | D | 0.736 | deleterious | None | None | None | None | N |
| S/G | 0.2443 | likely_benign | 0.2309 | benign | -0.559 | Destabilizing | 1.0 | D | 0.401 | neutral | None | None | None | None | N |
| S/H | 0.9364 | likely_pathogenic | 0.9256 | pathogenic | -1.079 | Destabilizing | 1.0 | D | 0.731 | deleterious | None | None | None | None | N |
| S/I | 0.7587 | likely_pathogenic | 0.6846 | pathogenic | -0.274 | Destabilizing | 1.0 | D | 0.668 | prob.neutral | None | None | None | None | N |
| S/K | 0.9935 | likely_pathogenic | 0.9917 | pathogenic | -0.595 | Destabilizing | 1.0 | D | 0.682 | prob.neutral | None | None | None | None | N |
| S/L | 0.4008 | ambiguous | 0.3217 | benign | -0.274 | Destabilizing | 1.0 | D | 0.654 | prob.neutral | N | 0.461437149 | None | None | N |
| S/M | 0.4992 | ambiguous | 0.4247 | ambiguous | 0.012 | Stabilizing | 1.0 | D | 0.735 | deleterious | None | None | None | None | N |
| S/N | 0.8131 | likely_pathogenic | 0.7767 | pathogenic | -0.298 | Destabilizing | 0.995 | D | 0.671 | prob.neutral | None | None | None | None | N |
| S/P | 0.9923 | likely_pathogenic | 0.9876 | pathogenic | -0.303 | Destabilizing | 1.0 | D | 0.695 | prob.delet. | N | 0.488113036 | None | None | N |
| S/Q | 0.9339 | likely_pathogenic | 0.922 | pathogenic | -0.596 | Destabilizing | 1.0 | D | 0.697 | prob.delet. | None | None | None | None | N |
| S/R | 0.9849 | likely_pathogenic | 0.9806 | pathogenic | -0.354 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | None | None | None | None | N |
| S/T | 0.1928 | likely_benign | 0.1798 | benign | -0.417 | Destabilizing | 0.96 | D | 0.483 | neutral | N | 0.486038309 | None | None | N |
| S/V | 0.5446 | ambiguous | 0.4845 | ambiguous | -0.303 | Destabilizing | 1.0 | D | 0.689 | prob.delet. | None | None | None | None | N |
| S/W | 0.9178 | likely_pathogenic | 0.8879 | pathogenic | -0.952 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | N |
| S/Y | 0.8075 | likely_pathogenic | 0.7605 | pathogenic | -0.698 | Destabilizing | 1.0 | D | 0.767 | 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.