Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30470 | 91633;91634;91635 | chr2:178551123;178551122;178551121 | chr2:179415850;179415849;179415848 |
| N2AB | 28829 | 86710;86711;86712 | chr2:178551123;178551122;178551121 | chr2:179415850;179415849;179415848 |
| N2A | 27902 | 83929;83930;83931 | chr2:178551123;178551122;178551121 | chr2:179415850;179415849;179415848 |
| N2B | 21405 | 64438;64439;64440 | chr2:178551123;178551122;178551121 | chr2:179415850;179415849;179415848 |
| Novex-1 | 21530 | 64813;64814;64815 | chr2:178551123;178551122;178551121 | chr2:179415850;179415849;179415848 |
| Novex-2 | 21597 | 65014;65015;65016 | chr2:178551123;178551122;178551121 | chr2:179415850;179415849;179415848 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/I | rs371081348  |
-0.117 | 1.0 | N | 0.783 | 0.424 | None | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 6.47E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/I | rs371081348 |
-0.117 | 1.0 | N | 0.783 | 0.424 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 7.25E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/I | rs371081348 |
-0.117 | 1.0 | N | 0.783 | 0.424 | None | gnomAD-4.0.0 | 1.97215E-05 | None | None | None | None | I | None | 7.24568E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/T | rs371081348 |
-0.638 | 1.0 | N | 0.756 | 0.407 | 0.545130385147 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 2.91E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/T | rs371081348 |
-0.638 | 1.0 | N | 0.756 | 0.407 | 0.545130385147 | gnomAD-4.0.0 | 1.59193E-06 | None | None | None | None | I | None | 0 | 2.28749E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.8796 | likely_pathogenic | 0.8868 | pathogenic | -0.983 | Destabilizing | 0.999 | D | 0.648 | neutral | None | None | None | None | I |
| R/C | 0.515 | ambiguous | 0.524 | ambiguous | -0.879 | Destabilizing | 1.0 | D | 0.748 | deleterious | None | None | None | None | I |
| R/D | 0.9764 | likely_pathogenic | 0.9759 | pathogenic | -0.014 | Destabilizing | 1.0 | D | 0.783 | deleterious | None | None | None | None | I |
| R/E | 0.8984 | likely_pathogenic | 0.8981 | pathogenic | 0.111 | Stabilizing | 0.999 | D | 0.679 | prob.neutral | None | None | None | None | I |
| R/F | 0.9304 | likely_pathogenic | 0.9325 | pathogenic | -0.87 | Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | I |
| R/G | 0.8458 | likely_pathogenic | 0.8496 | pathogenic | -1.287 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | N | 0.48207998 | None | None | I |
| R/H | 0.3476 | ambiguous | 0.3406 | ambiguous | -1.599 | Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | I |
| R/I | 0.7825 | likely_pathogenic | 0.7829 | pathogenic | -0.167 | Destabilizing | 1.0 | D | 0.783 | deleterious | N | 0.510592824 | None | None | I |
| R/K | 0.1975 | likely_benign | 0.1922 | benign | -0.858 | Destabilizing | 0.997 | D | 0.514 | neutral | N | 0.433766836 | None | None | I |
| R/L | 0.6673 | likely_pathogenic | 0.6712 | pathogenic | -0.167 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | I |
| R/M | 0.8005 | likely_pathogenic | 0.8122 | pathogenic | -0.445 | Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | I |
| R/N | 0.9473 | likely_pathogenic | 0.9498 | pathogenic | -0.312 | Destabilizing | 1.0 | D | 0.759 | deleterious | None | None | None | None | I |
| R/P | 0.7866 | likely_pathogenic | 0.7817 | pathogenic | -0.419 | Destabilizing | 1.0 | D | 0.767 | deleterious | None | None | None | None | I |
| R/Q | 0.3415 | ambiguous | 0.3399 | benign | -0.501 | Destabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | I |
| R/S | 0.9345 | likely_pathogenic | 0.9364 | pathogenic | -1.162 | Destabilizing | 1.0 | D | 0.76 | deleterious | N | 0.490100122 | None | None | I |
| R/T | 0.844 | likely_pathogenic | 0.8477 | pathogenic | -0.85 | Destabilizing | 1.0 | D | 0.756 | deleterious | N | 0.474034591 | None | None | I |
| R/V | 0.8313 | likely_pathogenic | 0.8317 | pathogenic | -0.419 | Destabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | I |
| R/W | 0.6315 | likely_pathogenic | 0.6421 | pathogenic | -0.5 | Destabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | I |
| R/Y | 0.8429 | likely_pathogenic | 0.8482 | pathogenic | -0.217 | Destabilizing | 1.0 | D | 0.775 | 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.