Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14156 | 42691;42692;42693 | chr2:178634033;178634032;178634031 | chr2:179498760;179498759;179498758 |
| N2AB | 12515 | 37768;37769;37770 | chr2:178634033;178634032;178634031 | chr2:179498760;179498759;179498758 |
| N2A | 11588 | 34987;34988;34989 | chr2:178634033;178634032;178634031 | chr2:179498760;179498759;179498758 |
| N2B | 5091 | 15496;15497;15498 | chr2:178634033;178634032;178634031 | chr2:179498760;179498759;179498758 |
| Novex-1 | 5216 | 15871;15872;15873 | chr2:178634033;178634032;178634031 | chr2:179498760;179498759;179498758 |
| Novex-2 | 5283 | 16072;16073;16074 | chr2:178634033;178634032;178634031 | chr2:179498760;179498759;179498758 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/C | rs878994668  |
None | 1.0 | D | 0.802 | 0.646 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| G/C | rs878994668 |
None | 1.0 | D | 0.802 | 0.646 | None | gnomAD-4.0.0 | 1.85985E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.54351E-06 | 0 | 0 |
| G/D | rs574305853 |
-1.281 | 1.0 | D | 0.789 | 0.691 | None | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | N | None | 1.29249E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| G/D | rs574305853 |
-1.281 | 1.0 | D | 0.789 | 0.691 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| G/D | rs574305853 |
-1.281 | 1.0 | D | 0.789 | 0.691 | None | gnomAD-4.0.0 | 1.85988E-06 | None | None | None | None | N | None | 2.6723E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 8.47844E-07 | 0 | 0 |
| G/R | None | None | 0.953 | D | 0.657 | 0.587 | 0.573134939963 | gnomAD-4.0.0 | 1.36889E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79937E-06 | 0 | 0 |
| G/S | rs878994668 |
-1.08 | 1.0 | D | 0.786 | 0.647 | 0.571763288708 | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 1.66279E-04 |
| G/S | rs878994668 |
-1.08 | 1.0 | D | 0.786 | 0.647 | 0.571763288708 | gnomAD-4.0.0 | 2.05334E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.31938E-05 | 1.65761E-05 |
| G/V | rs574305853 |
None | 1.0 | D | 0.788 | 0.723 | 0.757253434703 | gnomAD-4.0.0 | 6.8444E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99687E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/A | 0.5976 | likely_pathogenic | 0.5266 | ambiguous | -0.586 | Destabilizing | 1.0 | D | 0.67 | neutral | D | 0.621115702 | None | None | N |
| G/C | 0.7974 | likely_pathogenic | 0.7694 | pathogenic | -0.991 | Destabilizing | 1.0 | D | 0.802 | deleterious | D | 0.708543919 | None | None | N |
| G/D | 0.6497 | likely_pathogenic | 0.6215 | pathogenic | -1.037 | Destabilizing | 1.0 | D | 0.789 | deleterious | D | 0.634444837 | None | None | N |
| G/E | 0.6996 | likely_pathogenic | 0.6612 | pathogenic | -1.194 | Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | N |
| G/F | 0.9426 | likely_pathogenic | 0.9396 | pathogenic | -1.226 | Destabilizing | 1.0 | D | 0.823 | deleterious | None | None | None | None | N |
| G/H | 0.8456 | likely_pathogenic | 0.8642 | pathogenic | -0.838 | Destabilizing | 1.0 | D | 0.817 | deleterious | None | None | None | None | N |
| G/I | 0.9541 | likely_pathogenic | 0.9337 | pathogenic | -0.643 | Destabilizing | 1.0 | D | 0.823 | deleterious | None | None | None | None | N |
| G/K | 0.744 | likely_pathogenic | 0.7953 | pathogenic | -1.12 | Destabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | N |
| G/L | 0.9157 | likely_pathogenic | 0.891 | pathogenic | -0.643 | Destabilizing | 1.0 | D | 0.78 | deleterious | None | None | None | None | N |
| G/M | 0.9116 | likely_pathogenic | 0.892 | pathogenic | -0.519 | Destabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | N |
| G/N | 0.6441 | likely_pathogenic | 0.6195 | pathogenic | -0.768 | Destabilizing | 1.0 | D | 0.792 | deleterious | None | None | None | None | N |
| G/P | 0.9976 | likely_pathogenic | 0.9971 | pathogenic | -0.59 | Destabilizing | 1.0 | D | 0.812 | deleterious | None | None | None | None | N |
| G/Q | 0.771 | likely_pathogenic | 0.7838 | pathogenic | -1.107 | Destabilizing | 1.0 | D | 0.812 | deleterious | None | None | None | None | N |
| G/R | 0.6742 | likely_pathogenic | 0.7143 | pathogenic | -0.598 | Destabilizing | 0.953 | D | 0.657 | neutral | D | 0.567123456 | None | None | N |
| G/S | 0.4524 | ambiguous | 0.3812 | ambiguous | -0.902 | Destabilizing | 1.0 | D | 0.786 | deleterious | D | 0.633326849 | None | None | N |
| G/T | 0.755 | likely_pathogenic | 0.6943 | pathogenic | -1.002 | Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | N |
| G/V | 0.9112 | likely_pathogenic | 0.8712 | pathogenic | -0.59 | Destabilizing | 1.0 | D | 0.788 | deleterious | D | 0.708766789 | None | None | N |
| G/W | 0.8515 | likely_pathogenic | 0.8741 | pathogenic | -1.362 | Destabilizing | 1.0 | D | 0.794 | deleterious | None | None | None | None | N |
| G/Y | 0.8707 | likely_pathogenic | 0.875 | pathogenic | -1.042 | Destabilizing | 1.0 | D | 0.823 | 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.