Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26460 | 79603;79604;79605 | chr2:178566754;178566753;178566752 | chr2:179431481;179431480;179431479 |
| N2AB | 24819 | 74680;74681;74682 | chr2:178566754;178566753;178566752 | chr2:179431481;179431480;179431479 |
| N2A | 23892 | 71899;71900;71901 | chr2:178566754;178566753;178566752 | chr2:179431481;179431480;179431479 |
| N2B | 17395 | 52408;52409;52410 | chr2:178566754;178566753;178566752 | chr2:179431481;179431480;179431479 |
| Novex-1 | 17520 | 52783;52784;52785 | chr2:178566754;178566753;178566752 | chr2:179431481;179431480;179431479 |
| Novex-2 | 17587 | 52984;52985;52986 | chr2:178566754;178566753;178566752 | chr2:179431481;179431480;179431479 |
| 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/G | rs1406730761  |
-2.326 | 0.994 | D | 0.587 | 0.507 | 0.355034743287 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.58E-05 | None | 0 | None | 0 | 0 | 0 |
| R/G | rs1406730761 |
-2.326 | 0.994 | D | 0.587 | 0.507 | 0.355034743287 | gnomAD-4.0.0 | 1.36876E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.04261E-05 | None | 0 | 0 | 0 | 0 | 0 |
| R/K | None | None | 0.543 | N | 0.314 | 0.356 | 0.257786959452 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | I | None | 0 | 0 | None | 1.94099E-04 | 0 | None | 0 | 0 | 0 | 0 | 3.66327E-05 |
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 | 0.9487 | likely_pathogenic | 0.9301 | pathogenic | -1.827 | Destabilizing | 0.992 | D | 0.57 | neutral | None | None | None | None | I |
| R/C | 0.4576 | ambiguous | 0.4224 | ambiguous | -1.822 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | I |
| R/D | 0.9968 | likely_pathogenic | 0.996 | pathogenic | -0.826 | Destabilizing | 0.999 | D | 0.641 | neutral | None | None | None | None | I |
| R/E | 0.9395 | likely_pathogenic | 0.9183 | pathogenic | -0.633 | Destabilizing | 0.992 | D | 0.54 | neutral | None | None | None | None | I |
| R/F | 0.9582 | likely_pathogenic | 0.949 | pathogenic | -1.234 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | I |
| R/G | 0.9615 | likely_pathogenic | 0.9534 | pathogenic | -2.153 | Highly Destabilizing | 0.994 | D | 0.587 | neutral | D | 0.565175878 | None | None | I |
| R/H | 0.2868 | likely_benign | 0.2983 | benign | -2.093 | Highly Destabilizing | 1.0 | D | 0.592 | neutral | None | None | None | None | I |
| R/I | 0.8873 | likely_pathogenic | 0.8548 | pathogenic | -0.897 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | I |
| R/K | 0.4336 | ambiguous | 0.3626 | ambiguous | -1.348 | Destabilizing | 0.543 | D | 0.314 | neutral | N | 0.506428887 | None | None | I |
| R/L | 0.8102 | likely_pathogenic | 0.8015 | pathogenic | -0.897 | Destabilizing | 0.996 | D | 0.587 | neutral | None | None | None | None | I |
| R/M | 0.8973 | likely_pathogenic | 0.8482 | pathogenic | -1.386 | Destabilizing | 1.0 | D | 0.637 | neutral | D | 0.542716756 | None | None | I |
| R/N | 0.9826 | likely_pathogenic | 0.9772 | pathogenic | -1.153 | Destabilizing | 0.999 | D | 0.53 | neutral | None | None | None | None | I |
| R/P | 0.9991 | likely_pathogenic | 0.9991 | pathogenic | -1.195 | Destabilizing | 1.0 | D | 0.667 | neutral | None | None | None | None | I |
| R/Q | 0.2969 | likely_benign | 0.2492 | benign | -1.105 | Destabilizing | 0.998 | D | 0.529 | neutral | None | None | None | None | I |
| R/S | 0.9642 | likely_pathogenic | 0.9539 | pathogenic | -2.05 | Highly Destabilizing | 0.989 | D | 0.564 | neutral | N | 0.519746975 | None | None | I |
| R/T | 0.9365 | likely_pathogenic | 0.9052 | pathogenic | -1.659 | Destabilizing | 0.998 | D | 0.582 | neutral | N | 0.511126148 | None | None | I |
| R/V | 0.8971 | likely_pathogenic | 0.8696 | pathogenic | -1.195 | Destabilizing | 0.999 | D | 0.701 | prob.neutral | None | None | None | None | I |
| R/W | 0.6744 | likely_pathogenic | 0.6785 | pathogenic | -0.781 | Destabilizing | 1.0 | D | 0.666 | neutral | D | 0.542716756 | None | None | I |
| R/Y | 0.9141 | likely_pathogenic | 0.899 | pathogenic | -0.583 | Destabilizing | 1.0 | D | 0.7 | prob.neutral | 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.