Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21292 | 64099;64100;64101 | chr2:178587337;178587336;178587335 | chr2:179452064;179452063;179452062 |
| N2AB | 19651 | 59176;59177;59178 | chr2:178587337;178587336;178587335 | chr2:179452064;179452063;179452062 |
| N2A | 18724 | 56395;56396;56397 | chr2:178587337;178587336;178587335 | chr2:179452064;179452063;179452062 |
| N2B | 12227 | 36904;36905;36906 | chr2:178587337;178587336;178587335 | chr2:179452064;179452063;179452062 |
| Novex-1 | 12352 | 37279;37280;37281 | chr2:178587337;178587336;178587335 | chr2:179452064;179452063;179452062 |
| Novex-2 | 12419 | 37480;37481;37482 | chr2:178587337;178587336;178587335 | chr2:179452064;179452063;179452062 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/D | None | None | 0.999 | N | 0.556 | 0.338 | 0.27855597813 | gnomAD-4.0.0 | 6.92895E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.62743E-05 | None | 0 | 0 | 0 | 0 | 0 |
| N/H | None | None | 1.0 | N | 0.657 | 0.362 | 0.315609569513 | gnomAD-4.0.0 | 2.77219E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.72713E-06 | 1.16225E-05 | 0 |
| N/Y | None | None | 1.0 | N | 0.678 | 0.423 | 0.460526725402 | gnomAD-4.0.0 | 6.92895E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.08833E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.4148 | ambiguous | 0.48 | ambiguous | -0.381 | Destabilizing | 1.0 | D | 0.645 | neutral | None | None | None | None | N |
| N/C | 0.4048 | ambiguous | 0.4722 | ambiguous | 0.412 | Stabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | N |
| N/D | 0.1988 | likely_benign | 0.2225 | benign | -0.11 | Destabilizing | 0.999 | D | 0.556 | neutral | N | 0.427237935 | None | None | N |
| N/E | 0.5825 | likely_pathogenic | 0.6531 | pathogenic | -0.144 | Destabilizing | 0.999 | D | 0.67 | neutral | None | None | None | None | N |
| N/F | 0.554 | ambiguous | 0.6296 | pathogenic | -0.731 | Destabilizing | 1.0 | D | 0.688 | prob.neutral | None | None | None | None | N |
| N/G | 0.5582 | ambiguous | 0.5992 | pathogenic | -0.564 | Destabilizing | 0.999 | D | 0.505 | neutral | None | None | None | None | N |
| N/H | 0.21 | likely_benign | 0.2361 | benign | -0.693 | Destabilizing | 1.0 | D | 0.657 | neutral | N | 0.479555054 | None | None | N |
| N/I | 0.1972 | likely_benign | 0.2396 | benign | 0.016 | Stabilizing | 1.0 | D | 0.727 | prob.delet. | N | 0.499044892 | None | None | N |
| N/K | 0.5579 | ambiguous | 0.6206 | pathogenic | 0.048 | Stabilizing | 1.0 | D | 0.689 | prob.neutral | N | 0.457486271 | None | None | N |
| N/L | 0.2988 | likely_benign | 0.3329 | benign | 0.016 | Stabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | N |
| N/M | 0.3335 | likely_benign | 0.3927 | ambiguous | 0.513 | Stabilizing | 1.0 | D | 0.637 | neutral | None | None | None | None | N |
| N/P | 0.9535 | likely_pathogenic | 0.9612 | pathogenic | -0.09 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | N |
| N/Q | 0.5361 | ambiguous | 0.6025 | pathogenic | -0.428 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | N |
| N/R | 0.6347 | likely_pathogenic | 0.6838 | pathogenic | 0.092 | Stabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | N |
| N/S | 0.1638 | likely_benign | 0.1817 | benign | -0.144 | Destabilizing | 0.999 | D | 0.505 | neutral | N | 0.455350043 | None | None | N |
| N/T | 0.1908 | likely_benign | 0.218 | benign | -0.038 | Destabilizing | 0.999 | D | 0.668 | neutral | N | 0.461257295 | None | None | N |
| N/V | 0.2317 | likely_benign | 0.2894 | benign | -0.09 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | N |
| N/W | 0.8367 | likely_pathogenic | 0.8707 | pathogenic | -0.692 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | N |
| N/Y | 0.2071 | likely_benign | 0.2354 | benign | -0.435 | Destabilizing | 1.0 | D | 0.678 | prob.neutral | N | 0.447327993 | 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.