Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 9065 | 27418;27419;27420 | chr2:178712832;178712831;178712830 | chr2:179577559;179577558;179577557 |
| N2AB | 8748 | 26467;26468;26469 | chr2:178712832;178712831;178712830 | chr2:179577559;179577558;179577557 |
| N2A | 7821 | 23686;23687;23688 | chr2:178712832;178712831;178712830 | chr2:179577559;179577558;179577557 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/G | rs201229221  |
-2.414 | 0.035 | D | 0.445 | 0.386 | 0.751370582459 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.57E-05 | None | 0 | None | 0 | 0 | 0 |
| C/R | rs201229221 |
-1.327 | 0.988 | D | 0.724 | 0.57 | None | gnomAD-2.1.1 | 4.29E-05 | None | None | None | None | N | None | 8.27E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 7.82E-05 | 0 |
| C/R | rs201229221 |
-1.327 | 0.988 | D | 0.724 | 0.57 | None | gnomAD-3.1.2 | 7.23E-05 | None | None | None | None | N | None | 7.24E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.17609E-04 | 0 | 0 |
| C/R | rs201229221 |
-1.327 | 0.988 | D | 0.724 | 0.57 | None | gnomAD-4.0.0 | 1.62979E-04 | None | None | None | None | N | None | 6.67307E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.02578E-04 | 0 | 3.04214E-04 |
| C/S | None | None | 0.31 | N | 0.445 | 0.369 | 0.603850281814 | gnomAD-4.0.0 | 6.8422E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.52016E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/A | 0.5712 | likely_pathogenic | 0.5846 | pathogenic | -1.856 | Destabilizing | 0.759 | D | 0.49 | neutral | None | None | None | None | N |
| C/D | 0.8473 | likely_pathogenic | 0.8887 | pathogenic | -0.607 | Destabilizing | 0.982 | D | 0.706 | prob.neutral | None | None | None | None | N |
| C/E | 0.8697 | likely_pathogenic | 0.9043 | pathogenic | -0.444 | Destabilizing | 0.982 | D | 0.705 | prob.neutral | None | None | None | None | N |
| C/F | 0.1916 | likely_benign | 0.22 | benign | -1.099 | Destabilizing | 0.953 | D | 0.679 | prob.neutral | N | 0.474027096 | None | None | N |
| C/G | 0.297 | likely_benign | 0.3074 | benign | -2.207 | Highly Destabilizing | 0.035 | N | 0.445 | neutral | D | 0.52468799 | None | None | N |
| C/H | 0.5484 | ambiguous | 0.6065 | pathogenic | -2.207 | Highly Destabilizing | 0.982 | D | 0.689 | prob.neutral | None | None | None | None | N |
| C/I | 0.5055 | ambiguous | 0.5045 | ambiguous | -0.927 | Destabilizing | 0.991 | D | 0.679 | prob.neutral | None | None | None | None | N |
| C/K | 0.8479 | likely_pathogenic | 0.8903 | pathogenic | -1.096 | Destabilizing | 0.982 | D | 0.706 | prob.neutral | None | None | None | None | N |
| C/L | 0.5274 | ambiguous | 0.5573 | ambiguous | -0.927 | Destabilizing | 0.939 | D | 0.602 | neutral | None | None | None | None | N |
| C/M | 0.6702 | likely_pathogenic | 0.6812 | pathogenic | 0.088 | Stabilizing | 0.997 | D | 0.645 | neutral | None | None | None | None | N |
| C/N | 0.654 | likely_pathogenic | 0.684 | pathogenic | -1.297 | Destabilizing | 0.982 | D | 0.705 | prob.neutral | None | None | None | None | N |
| C/P | 0.9636 | likely_pathogenic | 0.975 | pathogenic | -1.212 | Destabilizing | 0.991 | D | 0.723 | prob.delet. | None | None | None | None | N |
| C/Q | 0.7017 | likely_pathogenic | 0.757 | pathogenic | -1.044 | Destabilizing | 0.991 | D | 0.728 | prob.delet. | None | None | None | None | N |
| C/R | 0.5217 | ambiguous | 0.6039 | pathogenic | -1.156 | Destabilizing | 0.988 | D | 0.724 | prob.delet. | D | 0.527285578 | None | None | N |
| C/S | 0.4157 | ambiguous | 0.4173 | ambiguous | -1.826 | Destabilizing | 0.31 | N | 0.445 | neutral | N | 0.516337866 | None | None | N |
| C/T | 0.5762 | likely_pathogenic | 0.5708 | pathogenic | -1.465 | Destabilizing | 0.884 | D | 0.603 | neutral | None | None | None | None | N |
| C/V | 0.4519 | ambiguous | 0.4538 | ambiguous | -1.212 | Destabilizing | 0.939 | D | 0.607 | neutral | None | None | None | None | N |
| C/W | 0.3572 | ambiguous | 0.4103 | ambiguous | -1.192 | Destabilizing | 0.997 | D | 0.632 | neutral | N | 0.492289375 | None | None | N |
| C/Y | 0.2171 | likely_benign | 0.2569 | benign | -1.149 | Destabilizing | 0.134 | N | 0.505 | neutral | N | 0.419731252 | 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.