Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15384 | 46375;46376;46377 | chr2:178620371;178620370;178620369 | chr2:179485098;179485097;179485096 |
| N2AB | 13743 | 41452;41453;41454 | chr2:178620371;178620370;178620369 | chr2:179485098;179485097;179485096 |
| N2A | 12816 | 38671;38672;38673 | chr2:178620371;178620370;178620369 | chr2:179485098;179485097;179485096 |
| N2B | 6319 | 19180;19181;19182 | chr2:178620371;178620370;178620369 | chr2:179485098;179485097;179485096 |
| Novex-1 | 6444 | 19555;19556;19557 | chr2:178620371;178620370;178620369 | chr2:179485098;179485097;179485096 |
| Novex-2 | 6511 | 19756;19757;19758 | chr2:178620371;178620370;178620369 | chr2:179485098;179485097;179485096 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/F | rs727505078  |
-1.828 | 1.0 | D | 0.749 | 0.555 | 0.757723905524 | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.6E-05 | None | 0 | None | 0 | 0 | 0 |
| L/F | rs727505078 |
-1.828 | 1.0 | D | 0.749 | 0.555 | 0.757723905524 | gnomAD-4.0.0 | 6.85478E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.52512E-05 | None | 0 | 0 | 0 | 0 | 0 |
| L/V | rs727505078 |
None | 0.999 | D | 0.546 | 0.416 | 0.671718306961 | gnomAD-4.0.0 | 1.02822E-05 | None | None | None | None | N | None | 0 | 2.24618E-05 | None | 0 | 0 | None | 0 | 0 | 1.26087E-05 | 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 | 0.9566 | likely_pathogenic | 0.947 | pathogenic | -2.93 | Highly Destabilizing | 0.999 | D | 0.681 | prob.neutral | None | None | None | None | N |
| L/C | 0.9123 | likely_pathogenic | 0.9079 | pathogenic | -2.089 | Highly Destabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | N |
| L/D | 0.9991 | likely_pathogenic | 0.9989 | pathogenic | -3.576 | Highly Destabilizing | 1.0 | D | 0.803 | deleterious | None | None | None | None | N |
| L/E | 0.996 | likely_pathogenic | 0.9957 | pathogenic | -3.273 | Highly Destabilizing | 1.0 | D | 0.812 | deleterious | None | None | None | None | N |
| L/F | 0.8416 | likely_pathogenic | 0.8505 | pathogenic | -1.786 | Destabilizing | 1.0 | D | 0.749 | deleterious | D | 0.672708403 | None | None | N |
| L/G | 0.9893 | likely_pathogenic | 0.9876 | pathogenic | -3.538 | Highly Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | N |
| L/H | 0.9915 | likely_pathogenic | 0.9912 | pathogenic | -3.101 | Highly Destabilizing | 1.0 | D | 0.797 | deleterious | D | 0.675846767 | None | None | N |
| L/I | 0.3046 | likely_benign | 0.3213 | benign | -1.113 | Destabilizing | 0.999 | D | 0.542 | neutral | D | 0.586611395 | None | None | N |
| L/K | 0.9917 | likely_pathogenic | 0.9916 | pathogenic | -2.316 | Highly Destabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | None | N |
| L/M | 0.4176 | ambiguous | 0.4268 | ambiguous | -1.103 | Destabilizing | 1.0 | D | 0.74 | deleterious | None | None | None | None | N |
| L/N | 0.9928 | likely_pathogenic | 0.9908 | pathogenic | -2.927 | Highly Destabilizing | 1.0 | D | 0.804 | deleterious | None | None | None | None | N |
| L/P | 0.9978 | likely_pathogenic | 0.9974 | pathogenic | -1.708 | Destabilizing | 1.0 | D | 0.804 | deleterious | D | 0.675846767 | None | None | N |
| L/Q | 0.9875 | likely_pathogenic | 0.9875 | pathogenic | -2.649 | Highly Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | N |
| L/R | 0.986 | likely_pathogenic | 0.9871 | pathogenic | -2.187 | Highly Destabilizing | 1.0 | D | 0.811 | deleterious | D | 0.675846767 | None | None | N |
| L/S | 0.9952 | likely_pathogenic | 0.9935 | pathogenic | -3.56 | Highly Destabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | N |
| L/T | 0.9746 | likely_pathogenic | 0.9704 | pathogenic | -3.098 | Highly Destabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | N |
| L/V | 0.3747 | ambiguous | 0.4045 | ambiguous | -1.708 | Destabilizing | 0.999 | D | 0.546 | neutral | D | 0.543503848 | None | None | N |
| L/W | 0.9886 | likely_pathogenic | 0.9894 | pathogenic | -2.247 | Highly Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | N |
| L/Y | 0.9813 | likely_pathogenic | 0.9812 | pathogenic | -1.998 | Destabilizing | 1.0 | D | 0.811 | 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.