Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1853 | 5782;5783;5784 | chr2:178776307;178776306;178776305 | chr2:179641034;179641033;179641032 |
| N2AB | 1853 | 5782;5783;5784 | chr2:178776307;178776306;178776305 | chr2:179641034;179641033;179641032 |
| N2A | 1853 | 5782;5783;5784 | chr2:178776307;178776306;178776305 | chr2:179641034;179641033;179641032 |
| N2B | 1807 | 5644;5645;5646 | chr2:178776307;178776306;178776305 | chr2:179641034;179641033;179641032 |
| Novex-1 | 1807 | 5644;5645;5646 | chr2:178776307;178776306;178776305 | chr2:179641034;179641033;179641032 |
| Novex-2 | 1807 | 5644;5645;5646 | chr2:178776307;178776306;178776305 | chr2:179641034;179641033;179641032 |
| Novex-3 | 1853 | 5782;5783;5784 | chr2:178776307;178776306;178776305 | chr2:179641034;179641033;179641032 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/F | rs778377360  |
-0.749 | 0.046 | N | 0.355 | 0.25 | 0.534955811369 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.8E-06 | 0 |
| L/F | rs778377360 |
-0.749 | 0.046 | N | 0.355 | 0.25 | 0.534955811369 | gnomAD-4.0.0 | 1.36824E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99308E-07 | 0 | 1.65585E-05 |
| L/P | None | None | 0.997 | N | 0.713 | 0.695 | 0.817510992187 | gnomAD-4.0.0 | 3.18144E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.71318E-06 | 0 | 0 |
| L/V | rs778377360 |
-0.416 | 0.939 | N | 0.582 | 0.188 | 0.54294064856 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.8E-06 | 0 |
| L/V | rs778377360 |
-0.416 | 0.939 | N | 0.582 | 0.188 | 0.54294064856 | 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 |
| L/V | rs778377360 |
-0.416 | 0.939 | N | 0.582 | 0.188 | 0.54294064856 | gnomAD-4.0.0 | 1.23922E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.69492E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.3663 | ambiguous | 0.3832 | ambiguous | -0.867 | Destabilizing | 0.976 | D | 0.639 | neutral | None | None | None | None | N |
| L/C | 0.784 | likely_pathogenic | 0.8039 | pathogenic | -0.733 | Destabilizing | 0.999 | D | 0.632 | neutral | None | None | None | None | N |
| L/D | 0.8784 | likely_pathogenic | 0.8919 | pathogenic | -0.358 | Destabilizing | 0.998 | D | 0.714 | prob.delet. | None | None | None | None | N |
| L/E | 0.6302 | likely_pathogenic | 0.6349 | pathogenic | -0.437 | Destabilizing | 0.998 | D | 0.711 | prob.delet. | None | None | None | None | N |
| L/F | 0.2735 | likely_benign | 0.2973 | benign | -0.725 | Destabilizing | 0.046 | N | 0.355 | neutral | N | 0.455722822 | None | None | N |
| L/G | 0.7213 | likely_pathogenic | 0.7231 | pathogenic | -1.061 | Destabilizing | 0.993 | D | 0.703 | prob.neutral | None | None | None | None | N |
| L/H | 0.5144 | ambiguous | 0.5391 | ambiguous | -0.245 | Destabilizing | 0.999 | D | 0.71 | prob.delet. | N | 0.486033241 | None | None | N |
| L/I | 0.1706 | likely_benign | 0.1879 | benign | -0.469 | Destabilizing | 0.885 | D | 0.538 | neutral | N | 0.470615133 | None | None | N |
| L/K | 0.5192 | ambiguous | 0.5075 | ambiguous | -0.569 | Destabilizing | 0.998 | D | 0.679 | prob.neutral | None | None | None | None | N |
| L/M | 0.1451 | likely_benign | 0.1511 | benign | -0.487 | Destabilizing | 0.993 | D | 0.589 | neutral | None | None | None | None | N |
| L/N | 0.597 | likely_pathogenic | 0.635 | pathogenic | -0.378 | Destabilizing | 0.998 | D | 0.713 | prob.delet. | None | None | None | None | N |
| L/P | 0.619 | likely_pathogenic | 0.602 | pathogenic | -0.568 | Destabilizing | 0.997 | D | 0.713 | prob.delet. | N | 0.432092253 | None | None | N |
| L/Q | 0.2995 | likely_benign | 0.3054 | benign | -0.614 | Destabilizing | 0.998 | D | 0.688 | prob.neutral | None | None | None | None | N |
| L/R | 0.445 | ambiguous | 0.4279 | ambiguous | 0.048 | Stabilizing | 0.997 | D | 0.69 | prob.neutral | N | 0.456325588 | None | None | N |
| L/S | 0.4679 | ambiguous | 0.5039 | ambiguous | -0.861 | Destabilizing | 0.993 | D | 0.681 | prob.neutral | None | None | None | None | N |
| L/T | 0.3262 | likely_benign | 0.3467 | ambiguous | -0.832 | Destabilizing | 0.993 | D | 0.623 | neutral | None | None | None | None | N |
| L/V | 0.1722 | likely_benign | 0.1834 | benign | -0.568 | Destabilizing | 0.939 | D | 0.582 | neutral | N | 0.424394909 | None | None | N |
| L/W | 0.5088 | ambiguous | 0.507 | ambiguous | -0.72 | Destabilizing | 0.999 | D | 0.687 | prob.neutral | None | None | None | None | N |
| L/Y | 0.5835 | likely_pathogenic | 0.608 | pathogenic | -0.498 | Destabilizing | 0.973 | D | 0.623 | 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.