Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22470 | 67633;67634;67635 | chr2:178579789;178579788;178579787 | chr2:179444516;179444515;179444514 |
| N2AB | 20829 | 62710;62711;62712 | chr2:178579789;178579788;178579787 | chr2:179444516;179444515;179444514 |
| N2A | 19902 | 59929;59930;59931 | chr2:178579789;178579788;178579787 | chr2:179444516;179444515;179444514 |
| N2B | 13405 | 40438;40439;40440 | chr2:178579789;178579788;178579787 | chr2:179444516;179444515;179444514 |
| Novex-1 | 13530 | 40813;40814;40815 | chr2:178579789;178579788;178579787 | chr2:179444516;179444515;179444514 |
| Novex-2 | 13597 | 41014;41015;41016 | chr2:178579789;178579788;178579787 | chr2:179444516;179444515;179444514 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs746559118  |
-2.56 | 0.549 | N | 0.679 | 0.37 | 0.505211317368 | gnomAD-2.1.1 | 8.08E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.11919E-04 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs746559118 |
-2.56 | 0.549 | N | 0.679 | 0.37 | 0.505211317368 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.94175E-04 | None | 0 | 0 | 0 | 2.07125E-04 | 0 |
| I/T | rs746559118 |
-2.56 | 0.549 | N | 0.679 | 0.37 | 0.505211317368 | gnomAD-4.0.0 | 4.33923E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 4.46728E-05 | None | 0 | 0 | 3.39128E-06 | 1.09798E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.6975 | likely_pathogenic | 0.6478 | pathogenic | -2.316 | Highly Destabilizing | 0.4 | N | 0.616 | neutral | None | None | None | None | N |
| I/C | 0.9451 | likely_pathogenic | 0.9221 | pathogenic | -1.548 | Destabilizing | 0.972 | D | 0.768 | deleterious | None | None | None | None | N |
| I/D | 0.9969 | likely_pathogenic | 0.9957 | pathogenic | -3.017 | Highly Destabilizing | 0.972 | D | 0.795 | deleterious | None | None | None | None | N |
| I/E | 0.9902 | likely_pathogenic | 0.9883 | pathogenic | -2.684 | Highly Destabilizing | 0.92 | D | 0.781 | deleterious | None | None | None | None | N |
| I/F | 0.2791 | likely_benign | 0.2277 | benign | -1.446 | Destabilizing | 0.379 | N | 0.643 | neutral | N | 0.509187315 | None | None | N |
| I/G | 0.9756 | likely_pathogenic | 0.9655 | pathogenic | -2.924 | Highly Destabilizing | 0.92 | D | 0.782 | deleterious | None | None | None | None | N |
| I/H | 0.9864 | likely_pathogenic | 0.9796 | pathogenic | -2.837 | Highly Destabilizing | 0.992 | D | 0.835 | deleterious | None | None | None | None | N |
| I/K | 0.9829 | likely_pathogenic | 0.979 | pathogenic | -1.863 | Destabilizing | 0.92 | D | 0.778 | deleterious | None | None | None | None | N |
| I/L | 0.0949 | likely_benign | 0.0841 | benign | -0.491 | Destabilizing | 0.001 | N | 0.204 | neutral | N | 0.336706357 | None | None | N |
| I/M | 0.1777 | likely_benign | 0.1503 | benign | -0.648 | Destabilizing | 0.81 | D | 0.612 | neutral | N | 0.514382491 | None | None | N |
| I/N | 0.9775 | likely_pathogenic | 0.9707 | pathogenic | -2.642 | Highly Destabilizing | 0.963 | D | 0.817 | deleterious | N | 0.487119636 | None | None | N |
| I/P | 0.9855 | likely_pathogenic | 0.9797 | pathogenic | -1.09 | Destabilizing | 0.972 | D | 0.815 | deleterious | None | None | None | None | N |
| I/Q | 0.9815 | likely_pathogenic | 0.9754 | pathogenic | -2.197 | Highly Destabilizing | 0.972 | D | 0.821 | deleterious | None | None | None | None | N |
| I/R | 0.9671 | likely_pathogenic | 0.9602 | pathogenic | -2.142 | Highly Destabilizing | 0.92 | D | 0.799 | deleterious | None | None | None | None | N |
| I/S | 0.9336 | likely_pathogenic | 0.9109 | pathogenic | -3.142 | Highly Destabilizing | 0.712 | D | 0.742 | deleterious | N | 0.486866147 | None | None | N |
| I/T | 0.7377 | likely_pathogenic | 0.6793 | pathogenic | -2.631 | Highly Destabilizing | 0.549 | D | 0.679 | prob.neutral | N | 0.486866147 | None | None | N |
| I/V | 0.1114 | likely_benign | 0.1019 | benign | -1.09 | Destabilizing | 0.045 | N | 0.349 | neutral | N | 0.432105037 | None | None | N |
| I/W | 0.9648 | likely_pathogenic | 0.9424 | pathogenic | -1.833 | Destabilizing | 0.992 | D | 0.833 | deleterious | None | None | None | None | N |
| I/Y | 0.911 | likely_pathogenic | 0.8809 | pathogenic | -1.583 | Destabilizing | 0.92 | D | 0.715 | prob.delet. | 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.