Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 9578 | 28957;28958;28959 | chr2:178709587;178709586;178709585 | chr2:179574314;179574313;179574312 |
| N2AB | 9261 | 28006;28007;28008 | chr2:178709587;178709586;178709585 | chr2:179574314;179574313;179574312 |
| N2A | 8334 | 25225;25226;25227 | chr2:178709587;178709586;178709585 | chr2:179574314;179574313;179574312 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | rs1370314453  |
-0.866 | 0.679 | None | 0.4 | 0.166 | 0.301789629655 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| T/A | rs1370314453 |
-0.866 | 0.679 | None | 0.4 | 0.166 | 0.301789629655 | gnomAD-4.0.0 | 1.59847E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.87781E-06 | 0 | 0 |
| T/K | None | None | 0.729 | None | 0.481 | 0.282 | 0.413113201963 | gnomAD-4.0.0 | 6.85554E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.014E-07 | 0 | 0 |
| T/M | rs184923756 |
-0.067 | 0.998 | None | 0.623 | 0.395 | None | gnomAD-2.1.1 | 1.53731E-04 | None | None | None | None | N | None | 0 | 2.83E-05 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 3.13063E-04 | 1.40766E-04 |
| T/M | rs184923756 |
-0.067 | 0.998 | None | 0.623 | 0.395 | None | gnomAD-3.1.2 | 2.62826E-04 | None | None | None | None | N | None | 4.82E-05 | 0 | 2.41228E-02 | 0 | 0 | None | 0 | 0 | 2.3517E-04 | 0 | 0 |
| T/M | rs184923756 |
-0.067 | 0.998 | None | 0.623 | 0.395 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| T/M | rs184923756 |
-0.067 | 0.998 | None | 0.623 | 0.395 | None | gnomAD-4.0.0 | 1.85601E-04 | None | None | None | None | N | None | 6.66702E-05 | 1.66756E-05 | None | 0 | 0 | None | 1.56362E-05 | 0 | 2.19974E-04 | 1.09914E-05 | 1.60395E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1937 | likely_benign | 0.1869 | benign | -0.782 | Destabilizing | 0.679 | D | 0.4 | neutral | None | None | None | None | N |
| T/C | 0.7731 | likely_pathogenic | 0.758 | pathogenic | -0.347 | Destabilizing | 0.047 | N | 0.384 | neutral | None | None | None | None | N |
| T/D | 0.8268 | likely_pathogenic | 0.7955 | pathogenic | 0.176 | Stabilizing | 0.021 | N | 0.323 | neutral | None | None | None | None | N |
| T/E | 0.7355 | likely_pathogenic | 0.7092 | pathogenic | 0.143 | Stabilizing | 0.083 | N | 0.32 | neutral | None | None | None | None | N |
| T/F | 0.5863 | likely_pathogenic | 0.5438 | ambiguous | -1.053 | Destabilizing | 0.993 | D | 0.645 | neutral | None | None | None | None | N |
| T/G | 0.6203 | likely_pathogenic | 0.5891 | pathogenic | -0.987 | Destabilizing | 0.932 | D | 0.573 | neutral | None | None | None | None | N |
| T/H | 0.5722 | likely_pathogenic | 0.5456 | ambiguous | -1.328 | Destabilizing | 0.98 | D | 0.639 | neutral | None | None | None | None | N |
| T/I | 0.481 | ambiguous | 0.4504 | ambiguous | -0.338 | Destabilizing | 0.98 | D | 0.641 | neutral | None | None | None | None | N |
| T/K | 0.6161 | likely_pathogenic | 0.6118 | pathogenic | -0.501 | Destabilizing | 0.729 | D | 0.481 | neutral | None | None | None | None | N |
| T/L | 0.2813 | likely_benign | 0.259 | benign | -0.338 | Destabilizing | 0.872 | D | 0.522 | neutral | None | None | None | None | N |
| T/M | 0.2155 | likely_benign | 0.1987 | benign | 0.044 | Stabilizing | 0.998 | D | 0.623 | neutral | None | None | None | None | N |
| T/N | 0.3558 | ambiguous | 0.3258 | benign | -0.319 | Destabilizing | 0.872 | D | 0.467 | neutral | None | None | None | None | N |
| T/P | 0.3705 | ambiguous | 0.3388 | benign | -0.455 | Destabilizing | 0.969 | D | 0.647 | neutral | None | None | None | None | N |
| T/Q | 0.5307 | ambiguous | 0.5236 | ambiguous | -0.544 | Destabilizing | 0.209 | N | 0.391 | neutral | None | None | None | None | N |
| T/R | 0.5157 | ambiguous | 0.5058 | ambiguous | -0.287 | Destabilizing | 0.149 | N | 0.388 | neutral | None | None | None | None | N |
| T/S | 0.2014 | likely_benign | 0.1929 | benign | -0.645 | Destabilizing | 0.679 | D | 0.446 | neutral | None | None | None | None | N |
| T/V | 0.3577 | ambiguous | 0.3289 | benign | -0.455 | Destabilizing | 0.872 | D | 0.455 | neutral | None | None | None | None | N |
| T/W | 0.9029 | likely_pathogenic | 0.8789 | pathogenic | -0.957 | Destabilizing | 0.998 | D | 0.657 | neutral | None | None | None | None | N |
| T/Y | 0.6417 | likely_pathogenic | 0.6139 | pathogenic | -0.718 | Destabilizing | 0.993 | D | 0.648 | 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.