Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2948 | 9067;9068;9069 | chr2:178769739;178769738;178769737 | chr2:179634466;179634465;179634464 |
| N2AB | 2948 | 9067;9068;9069 | chr2:178769739;178769738;178769737 | chr2:179634466;179634465;179634464 |
| N2A | 2948 | 9067;9068;9069 | chr2:178769739;178769738;178769737 | chr2:179634466;179634465;179634464 |
| N2B | 2902 | 8929;8930;8931 | chr2:178769739;178769738;178769737 | chr2:179634466;179634465;179634464 |
| Novex-1 | 2902 | 8929;8930;8931 | chr2:178769739;178769738;178769737 | chr2:179634466;179634465;179634464 |
| Novex-2 | 2902 | 8929;8930;8931 | chr2:178769739;178769738;178769737 | chr2:179634466;179634465;179634464 |
| Novex-3 | 2948 | 9067;9068;9069 | chr2:178769739;178769738;178769737 | chr2:179634466;179634465;179634464 |
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/L | rs397517763  |
-0.312 | 0.586 | D | 0.574 | 0.497 | 0.754234975006 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.85E-06 | 0 |
| S/L | rs397517763 |
-0.312 | 0.586 | D | 0.574 | 0.497 | 0.754234975006 | gnomAD-4.0.0 | 7.52511E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.89257E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0571 | likely_benign | 0.0712 | benign | -0.74 | Destabilizing | 0.001 | N | 0.172 | neutral | N | 0.480442911 | None | None | N |
| S/C | 0.1461 | likely_benign | 0.1591 | benign | -0.561 | Destabilizing | 0.947 | D | 0.658 | neutral | None | None | None | None | N |
| S/D | 0.6906 | likely_pathogenic | 0.698 | pathogenic | -0.471 | Destabilizing | 0.7 | D | 0.505 | neutral | None | None | None | None | N |
| S/E | 0.6113 | likely_pathogenic | 0.6326 | pathogenic | -0.499 | Destabilizing | 0.399 | N | 0.479 | neutral | None | None | None | None | N |
| S/F | 0.4841 | ambiguous | 0.5018 | ambiguous | -1.08 | Destabilizing | 0.826 | D | 0.742 | deleterious | None | None | None | None | N |
| S/G | 0.1416 | likely_benign | 0.1469 | benign | -0.947 | Destabilizing | 0.121 | N | 0.491 | neutral | None | None | None | None | N |
| S/H | 0.6501 | likely_pathogenic | 0.649 | pathogenic | -1.469 | Destabilizing | 0.982 | D | 0.659 | neutral | None | None | None | None | N |
| S/I | 0.3154 | likely_benign | 0.3479 | ambiguous | -0.3 | Destabilizing | 0.7 | D | 0.736 | prob.delet. | None | None | None | None | N |
| S/K | 0.771 | likely_pathogenic | 0.788 | pathogenic | -0.707 | Destabilizing | 0.399 | N | 0.476 | neutral | None | None | None | None | N |
| S/L | 0.1686 | likely_benign | 0.1835 | benign | -0.3 | Destabilizing | 0.586 | D | 0.574 | neutral | D | 0.622292163 | None | None | N |
| S/M | 0.2638 | likely_benign | 0.2912 | benign | 0.093 | Stabilizing | 0.947 | D | 0.662 | neutral | None | None | None | None | N |
| S/N | 0.3087 | likely_benign | 0.2988 | benign | -0.654 | Destabilizing | 0.826 | D | 0.549 | neutral | None | None | None | None | N |
| S/P | 0.935 | likely_pathogenic | 0.9219 | pathogenic | -0.415 | Destabilizing | 0.638 | D | 0.715 | prob.delet. | D | 0.622800589 | None | None | N |
| S/Q | 0.6092 | likely_pathogenic | 0.6279 | pathogenic | -0.909 | Destabilizing | 0.826 | D | 0.602 | neutral | None | None | None | None | N |
| S/R | 0.6814 | likely_pathogenic | 0.6972 | pathogenic | -0.515 | Destabilizing | 0.7 | D | 0.717 | prob.delet. | None | None | None | None | N |
| S/T | 0.1017 | likely_benign | 0.1059 | benign | -0.691 | Destabilizing | 0.201 | N | 0.457 | neutral | N | 0.513099604 | None | None | N |
| S/V | 0.2757 | likely_benign | 0.3114 | benign | -0.415 | Destabilizing | 0.25 | N | 0.586 | neutral | None | None | None | None | N |
| S/W | 0.756 | likely_pathogenic | 0.7676 | pathogenic | -1.03 | Destabilizing | 0.99 | D | 0.671 | neutral | D | 0.663104683 | None | None | N |
| S/Y | 0.4381 | ambiguous | 0.4667 | ambiguous | -0.765 | Destabilizing | 0.826 | D | 0.745 | 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.