Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3232 | 9919;9920;9921 | chr2:178766390;178766389;178766388 | chr2:179631117;179631116;179631115 |
| N2AB | 3232 | 9919;9920;9921 | chr2:178766390;178766389;178766388 | chr2:179631117;179631116;179631115 |
| N2A | 3232 | 9919;9920;9921 | chr2:178766390;178766389;178766388 | chr2:179631117;179631116;179631115 |
| N2B | 3186 | 9781;9782;9783 | chr2:178766390;178766389;178766388 | chr2:179631117;179631116;179631115 |
| Novex-1 | 3186 | 9781;9782;9783 | chr2:178766390;178766389;178766388 | chr2:179631117;179631116;179631115 |
| Novex-2 | 3186 | 9781;9782;9783 | chr2:178766390;178766389;178766388 | chr2:179631117;179631116;179631115 |
| Novex-3 | 3232 | 9919;9920;9921 | chr2:178766390;178766389;178766388 | chr2:179631117;179631116;179631115 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/C | rs537306539  |
-0.1 | 0.946 | N | 0.285 | 0.141 | 0.422524665647 | gnomAD-2.1.1 | 2.83E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 6.53E-05 | None | 0 | 4.65E-05 | 0 |
| Y/C | rs537306539 |
-0.1 | 0.946 | N | 0.285 | 0.141 | 0.422524665647 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| Y/C | rs537306539 |
-0.1 | 0.946 | N | 0.285 | 0.141 | 0.422524665647 | gnomAD-4.0.0 | 1.4279E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.61413E-05 | 3.29518E-05 | 1.6039E-05 |
| Y/S | rs537306539 |
-0.806 | 0.175 | N | 0.351 | 0.145 | 0.355658859761 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| Y/S | rs537306539 |
-0.806 | 0.175 | N | 0.351 | 0.145 | 0.355658859761 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| Y/S | rs537306539 |
-0.806 | 0.175 | N | 0.351 | 0.145 | 0.355658859761 | gnomAD-4.0.0 | 6.56625E-06 | None | None | None | None | N | None | 2.40547E-05 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.6424 | likely_pathogenic | 0.6152 | pathogenic | -1.954 | Destabilizing | 0.104 | N | 0.29 | neutral | None | None | None | None | N |
| Y/C | 0.2607 | likely_benign | 0.2687 | benign | -0.426 | Destabilizing | 0.946 | D | 0.285 | neutral | N | 0.344364775 | None | None | N |
| Y/D | 0.5393 | ambiguous | 0.5612 | ambiguous | -0.277 | Destabilizing | 0.175 | N | 0.371 | neutral | N | 0.343267797 | None | None | N |
| Y/E | 0.7619 | likely_pathogenic | 0.7332 | pathogenic | -0.241 | Destabilizing | 0.22 | N | 0.35 | neutral | None | None | None | None | N |
| Y/F | 0.1015 | likely_benign | 0.0834 | benign | -0.975 | Destabilizing | 0.001 | N | 0.171 | neutral | N | 0.349256253 | None | None | N |
| Y/G | 0.6992 | likely_pathogenic | 0.7099 | pathogenic | -2.233 | Highly Destabilizing | 0.22 | N | 0.355 | neutral | None | None | None | None | N |
| Y/H | 0.1883 | likely_benign | 0.1664 | benign | -0.732 | Destabilizing | 0.001 | N | 0.143 | neutral | N | 0.343025127 | None | None | N |
| Y/I | 0.588 | likely_pathogenic | 0.468 | ambiguous | -1.144 | Destabilizing | 0.004 | N | 0.243 | neutral | None | None | None | None | N |
| Y/K | 0.6992 | likely_pathogenic | 0.6371 | pathogenic | -0.647 | Destabilizing | 0.124 | N | 0.327 | neutral | None | None | None | None | N |
| Y/L | 0.5274 | ambiguous | 0.4903 | ambiguous | -1.144 | Destabilizing | 0.055 | N | 0.282 | neutral | None | None | None | None | N |
| Y/M | 0.7108 | likely_pathogenic | 0.631 | pathogenic | -0.69 | Destabilizing | 0.667 | D | 0.315 | neutral | None | None | None | None | N |
| Y/N | 0.2945 | likely_benign | 0.2644 | benign | -0.783 | Destabilizing | 0.096 | N | 0.377 | neutral | N | 0.348069974 | None | None | N |
| Y/P | 0.9335 | likely_pathogenic | 0.9839 | pathogenic | -1.404 | Destabilizing | 0.859 | D | 0.337 | neutral | None | None | None | None | N |
| Y/Q | 0.5842 | likely_pathogenic | 0.5187 | ambiguous | -0.804 | Destabilizing | 0.497 | N | 0.369 | neutral | None | None | None | None | N |
| Y/R | 0.4447 | ambiguous | 0.4061 | ambiguous | -0.156 | Destabilizing | None | N | 0.208 | neutral | None | None | None | None | N |
| Y/S | 0.3426 | ambiguous | 0.3101 | benign | -1.32 | Destabilizing | 0.175 | N | 0.351 | neutral | N | 0.334607203 | None | None | N |
| Y/T | 0.568 | likely_pathogenic | 0.4545 | ambiguous | -1.195 | Destabilizing | 0.364 | N | 0.347 | neutral | None | None | None | None | N |
| Y/V | 0.4866 | ambiguous | 0.3957 | ambiguous | -1.404 | Destabilizing | 0.055 | N | 0.302 | neutral | None | None | None | None | N |
| Y/W | 0.5016 | ambiguous | 0.4904 | ambiguous | -0.698 | Destabilizing | 0.958 | D | 0.385 | neutral | 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.