Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22448 | 67567;67568;67569 | chr2:178579945;178579944;178579943 | chr2:179444672;179444671;179444670 |
| N2AB | 20807 | 62644;62645;62646 | chr2:178579945;178579944;178579943 | chr2:179444672;179444671;179444670 |
| N2A | 19880 | 59863;59864;59865 | chr2:178579945;178579944;178579943 | chr2:179444672;179444671;179444670 |
| N2B | 13383 | 40372;40373;40374 | chr2:178579945;178579944;178579943 | chr2:179444672;179444671;179444670 |
| Novex-1 | 13508 | 40747;40748;40749 | chr2:178579945;178579944;178579943 | chr2:179444672;179444671;179444670 |
| Novex-2 | 13575 | 40948;40949;40950 | chr2:178579945;178579944;178579943 | chr2:179444672;179444671;179444670 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/S | rs2047323324  |
None | 0.999 | N | 0.627 | 0.215 | 0.367992661779 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/S | rs2047323324 |
None | 0.999 | N | 0.627 | 0.215 | 0.367992661779 | gnomAD-4.0.0 | 5.07546E-06 | None | None | None | None | N | None | 6.98983E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.40275E-05 |
| A/V | None | None | 0.999 | N | 0.673 | 0.304 | 0.431712495121 | gnomAD-4.0.0 | 1.36899E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.7994E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.7068 | likely_pathogenic | 0.6704 | pathogenic | -1.776 | Destabilizing | 1.0 | D | 0.782 | deleterious | None | None | None | None | N |
| A/D | 0.9882 | likely_pathogenic | 0.9878 | pathogenic | -2.41 | Highly Destabilizing | 1.0 | D | 0.805 | deleterious | N | 0.502115884 | None | None | N |
| A/E | 0.9757 | likely_pathogenic | 0.9749 | pathogenic | -2.335 | Highly Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | N |
| A/F | 0.9035 | likely_pathogenic | 0.8921 | pathogenic | -1.084 | Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | N |
| A/G | 0.5754 | likely_pathogenic | 0.5309 | ambiguous | -1.534 | Destabilizing | 0.999 | D | 0.576 | neutral | N | 0.517361294 | None | None | N |
| A/H | 0.9904 | likely_pathogenic | 0.989 | pathogenic | -1.499 | Destabilizing | 1.0 | D | 0.777 | deleterious | None | None | None | None | N |
| A/I | 0.3552 | ambiguous | 0.3363 | benign | -0.442 | Destabilizing | 1.0 | D | 0.799 | deleterious | None | None | None | None | N |
| A/K | 0.9933 | likely_pathogenic | 0.9924 | pathogenic | -1.311 | Destabilizing | 1.0 | D | 0.767 | deleterious | None | None | None | None | N |
| A/L | 0.515 | ambiguous | 0.4786 | ambiguous | -0.442 | Destabilizing | 1.0 | D | 0.804 | deleterious | None | None | None | None | N |
| A/M | 0.6833 | likely_pathogenic | 0.6648 | pathogenic | -0.797 | Destabilizing | 1.0 | D | 0.822 | deleterious | None | None | None | None | N |
| A/N | 0.9412 | likely_pathogenic | 0.9417 | pathogenic | -1.457 | Destabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | N |
| A/P | 0.7156 | likely_pathogenic | 0.6473 | pathogenic | -0.662 | Destabilizing | 1.0 | D | 0.797 | deleterious | N | 0.478629548 | None | None | N |
| A/Q | 0.9725 | likely_pathogenic | 0.9709 | pathogenic | -1.54 | Destabilizing | 1.0 | D | 0.809 | deleterious | None | None | None | None | N |
| A/R | 0.9789 | likely_pathogenic | 0.9776 | pathogenic | -1.098 | Destabilizing | 1.0 | D | 0.802 | deleterious | None | None | None | None | N |
| A/S | 0.3704 | ambiguous | 0.3624 | ambiguous | -1.828 | Destabilizing | 0.999 | D | 0.627 | neutral | N | 0.467375404 | None | None | N |
| A/T | 0.4071 | ambiguous | 0.3828 | ambiguous | -1.655 | Destabilizing | 1.0 | D | 0.757 | deleterious | N | 0.507664375 | None | None | N |
| A/V | 0.1805 | likely_benign | 0.1678 | benign | -0.662 | Destabilizing | 0.999 | D | 0.673 | prob.neutral | N | 0.474629237 | None | None | N |
| A/W | 0.9943 | likely_pathogenic | 0.9931 | pathogenic | -1.5 | Destabilizing | 1.0 | D | 0.729 | deleterious | None | None | None | None | N |
| A/Y | 0.9717 | likely_pathogenic | 0.9664 | pathogenic | -1.066 | Destabilizing | 1.0 | D | 0.818 | 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.