Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17351 | 52276;52277;52278 | chr2:178609259;178609258;178609257 | chr2:179473986;179473985;179473984 |
| N2AB | 15710 | 47353;47354;47355 | chr2:178609259;178609258;178609257 | chr2:179473986;179473985;179473984 |
| N2A | 14783 | 44572;44573;44574 | chr2:178609259;178609258;178609257 | chr2:179473986;179473985;179473984 |
| N2B | 8286 | 25081;25082;25083 | chr2:178609259;178609258;178609257 | chr2:179473986;179473985;179473984 |
| Novex-1 | 8411 | 25456;25457;25458 | chr2:178609259;178609258;178609257 | chr2:179473986;179473985;179473984 |
| Novex-2 | 8478 | 25657;25658;25659 | chr2:178609259;178609258;178609257 | chr2:179473986;179473985;179473984 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs565423253  |
-2.163 | 0.002 | N | 0.321 | 0.121 | 0.136095386433 | gnomAD-2.1.1 | 6.79E-05 | None | None | None | None | I | None | 0 | 3.23415E-04 | None | 0 | 2.89721E-04 | None | 5.94E-05 | None | 0 | 9.36E-06 | 0 |
| V/A | rs565423253 |
-2.163 | 0.002 | N | 0.321 | 0.121 | 0.136095386433 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | I | None | 0 | 1.9698E-04 | 0 | 0 | 3.89257E-04 | None | 0 | 0 | 0 | 0 | 0 |
| V/A | rs565423253 |
-2.163 | 0.002 | N | 0.321 | 0.121 | 0.136095386433 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| V/A | rs565423253 |
-2.163 | 0.002 | N | 0.321 | 0.121 | 0.136095386433 | gnomAD-4.0.0 | 1.29841E-05 | None | None | None | None | I | None | 0 | 2.29109E-04 | None | 0 | 1.36482E-04 | None | 0 | 0 | 1.74251E-06 | 1.30969E-05 | 0 |
| V/G | rs565423253 |
None | 0.468 | N | 0.779 | 0.387 | None | gnomAD-4.0.0 | 5.0422E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.48232E-06 | 0 | 0 |
| V/I | rs765525785 |
-0.686 | 0.172 | D | 0.526 | 0.24 | 0.508455578974 | gnomAD-2.1.1 | 5.27E-06 | None | None | None | None | I | None | 0 | 4.19E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/I | rs765525785 |
-0.686 | 0.172 | D | 0.526 | 0.24 | 0.508455578974 | gnomAD-4.0.0 | 1.80083E-06 | None | None | None | None | I | None | 0 | 3.14406E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.2126 | likely_benign | 0.1647 | benign | -2.23 | Highly Destabilizing | 0.002 | N | 0.321 | neutral | N | 0.428518519 | None | None | I |
| V/C | 0.892 | likely_pathogenic | 0.8558 | pathogenic | -1.84 | Destabilizing | 0.947 | D | 0.811 | deleterious | None | None | None | None | I |
| V/D | 0.9933 | likely_pathogenic | 0.986 | pathogenic | -2.919 | Highly Destabilizing | 0.638 | D | 0.849 | deleterious | N | 0.521912336 | None | None | I |
| V/E | 0.988 | likely_pathogenic | 0.9777 | pathogenic | -2.737 | Highly Destabilizing | 0.7 | D | 0.822 | deleterious | None | None | None | None | I |
| V/F | 0.9518 | likely_pathogenic | 0.9244 | pathogenic | -1.315 | Destabilizing | 0.781 | D | 0.803 | deleterious | N | 0.521658847 | None | None | I |
| V/G | 0.5872 | likely_pathogenic | 0.4996 | ambiguous | -2.725 | Highly Destabilizing | 0.468 | N | 0.779 | deleterious | N | 0.503554592 | None | None | I |
| V/H | 0.9983 | likely_pathogenic | 0.9967 | pathogenic | -2.379 | Highly Destabilizing | 0.982 | D | 0.857 | deleterious | None | None | None | None | I |
| V/I | 0.2191 | likely_benign | 0.2141 | benign | -0.86 | Destabilizing | 0.172 | N | 0.526 | neutral | D | 0.523424128 | None | None | I |
| V/K | 0.9952 | likely_pathogenic | 0.9913 | pathogenic | -1.922 | Destabilizing | 0.7 | D | 0.826 | deleterious | None | None | None | None | I |
| V/L | 0.7475 | likely_pathogenic | 0.6607 | pathogenic | -0.86 | Destabilizing | 0.094 | N | 0.617 | neutral | N | 0.509206823 | None | None | I |
| V/M | 0.786 | likely_pathogenic | 0.7251 | pathogenic | -0.966 | Destabilizing | 0.826 | D | 0.762 | deleterious | None | None | None | None | I |
| V/N | 0.9834 | likely_pathogenic | 0.9673 | pathogenic | -2.155 | Highly Destabilizing | 0.826 | D | 0.855 | deleterious | None | None | None | None | I |
| V/P | 0.9928 | likely_pathogenic | 0.9863 | pathogenic | -1.29 | Destabilizing | 0.7 | D | 0.832 | deleterious | None | None | None | None | I |
| V/Q | 0.9904 | likely_pathogenic | 0.9815 | pathogenic | -2.074 | Highly Destabilizing | 0.826 | D | 0.841 | deleterious | None | None | None | None | I |
| V/R | 0.9887 | likely_pathogenic | 0.9791 | pathogenic | -1.62 | Destabilizing | 0.7 | D | 0.847 | deleterious | None | None | None | None | I |
| V/S | 0.7607 | likely_pathogenic | 0.6565 | pathogenic | -2.734 | Highly Destabilizing | 0.539 | D | 0.775 | deleterious | None | None | None | None | I |
| V/T | 0.5363 | ambiguous | 0.4356 | ambiguous | -2.426 | Highly Destabilizing | 0.25 | N | 0.624 | neutral | None | None | None | None | I |
| V/W | 0.9993 | likely_pathogenic | 0.9985 | pathogenic | -1.799 | Destabilizing | 0.982 | D | 0.828 | deleterious | None | None | None | None | I |
| V/Y | 0.9948 | likely_pathogenic | 0.9904 | pathogenic | -1.471 | Destabilizing | 0.826 | D | 0.801 | deleterious | None | None | None | None | I |
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.