Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27393 | 82402;82403;82404 | chr2:178563955;178563954;178563953 | chr2:179428682;179428681;179428680 |
| N2AB | 25752 | 77479;77480;77481 | chr2:178563955;178563954;178563953 | chr2:179428682;179428681;179428680 |
| N2A | 24825 | 74698;74699;74700 | chr2:178563955;178563954;178563953 | chr2:179428682;179428681;179428680 |
| N2B | 18328 | 55207;55208;55209 | chr2:178563955;178563954;178563953 | chr2:179428682;179428681;179428680 |
| Novex-1 | 18453 | 55582;55583;55584 | chr2:178563955;178563954;178563953 | chr2:179428682;179428681;179428680 |
| Novex-2 | 18520 | 55783;55784;55785 | chr2:178563955;178563954;178563953 | chr2:179428682;179428681;179428680 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | None | None | 0.014 | D | 0.28 | 0.26 | 0.242825505644 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 6.33473E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/L | rs1267590455  |
-0.616 | 0.698 | N | 0.608 | 0.413 | 0.644453097843 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| P/L | rs1267590455 |
-0.616 | 0.698 | N | 0.608 | 0.413 | 0.644453097843 | gnomAD-4.0.0 | 1.59142E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43275E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0822 | likely_benign | 0.0819 | benign | -1.931 | Destabilizing | 0.014 | N | 0.28 | neutral | D | 0.527122502 | None | None | N |
| P/C | 0.4479 | ambiguous | 0.4616 | ambiguous | -1.286 | Destabilizing | 0.994 | D | 0.7 | prob.neutral | None | None | None | None | N |
| P/D | 0.6345 | likely_pathogenic | 0.6285 | pathogenic | -2.266 | Highly Destabilizing | 0.926 | D | 0.529 | neutral | None | None | None | None | N |
| P/E | 0.3081 | likely_benign | 0.2984 | benign | -2.124 | Highly Destabilizing | 0.86 | D | 0.483 | neutral | None | None | None | None | N |
| P/F | 0.4719 | ambiguous | 0.4911 | ambiguous | -1.298 | Destabilizing | 0.978 | D | 0.696 | prob.neutral | None | None | None | None | N |
| P/G | 0.4153 | ambiguous | 0.4204 | ambiguous | -2.363 | Highly Destabilizing | 0.754 | D | 0.534 | neutral | None | None | None | None | N |
| P/H | 0.1946 | likely_benign | 0.1924 | benign | -1.854 | Destabilizing | 0.019 | N | 0.411 | neutral | None | None | None | None | N |
| P/I | 0.2733 | likely_benign | 0.2437 | benign | -0.763 | Destabilizing | 0.956 | D | 0.672 | neutral | None | None | None | None | N |
| P/K | 0.2425 | likely_benign | 0.2396 | benign | -1.675 | Destabilizing | 0.86 | D | 0.514 | neutral | None | None | None | None | N |
| P/L | 0.1176 | likely_benign | 0.1127 | benign | -0.763 | Destabilizing | 0.698 | D | 0.608 | neutral | N | 0.498558982 | None | None | N |
| P/M | 0.2803 | likely_benign | 0.267 | benign | -0.646 | Destabilizing | 0.998 | D | 0.66 | neutral | None | None | None | None | N |
| P/N | 0.4515 | ambiguous | 0.4466 | ambiguous | -1.758 | Destabilizing | 0.956 | D | 0.595 | neutral | None | None | None | None | N |
| P/Q | 0.1595 | likely_benign | 0.1512 | benign | -1.753 | Destabilizing | 0.97 | D | 0.591 | neutral | N | 0.487949919 | None | None | N |
| P/R | 0.1591 | likely_benign | 0.1558 | benign | -1.303 | Destabilizing | 0.942 | D | 0.614 | neutral | N | 0.485961683 | None | None | N |
| P/S | 0.1594 | likely_benign | 0.1619 | benign | -2.298 | Highly Destabilizing | 0.698 | D | 0.481 | neutral | N | 0.485214441 | None | None | N |
| P/T | 0.1347 | likely_benign | 0.1304 | benign | -2.024 | Highly Destabilizing | 0.822 | D | 0.497 | neutral | N | 0.487936692 | None | None | N |
| P/V | 0.1899 | likely_benign | 0.1729 | benign | -1.124 | Destabilizing | 0.754 | D | 0.568 | neutral | None | None | None | None | N |
| P/W | 0.6751 | likely_pathogenic | 0.693 | pathogenic | -1.631 | Destabilizing | 0.998 | D | 0.721 | prob.delet. | None | None | None | None | N |
| P/Y | 0.4304 | ambiguous | 0.4393 | ambiguous | -1.289 | Destabilizing | 0.956 | D | 0.661 | 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.