Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15408 | 46447;46448;46449 | chr2:178620299;178620298;178620297 | chr2:179485026;179485025;179485024 |
| N2AB | 13767 | 41524;41525;41526 | chr2:178620299;178620298;178620297 | chr2:179485026;179485025;179485024 |
| N2A | 12840 | 38743;38744;38745 | chr2:178620299;178620298;178620297 | chr2:179485026;179485025;179485024 |
| N2B | 6343 | 19252;19253;19254 | chr2:178620299;178620298;178620297 | chr2:179485026;179485025;179485024 |
| Novex-1 | 6468 | 19627;19628;19629 | chr2:178620299;178620298;178620297 | chr2:179485026;179485025;179485024 |
| Novex-2 | 6535 | 19828;19829;19830 | chr2:178620299;178620298;178620297 | chr2:179485026;179485025;179485024 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/D | rs537697585  |
-1.714 | 1.0 | D | 0.849 | 0.739 | 0.826406704241 | gnomAD-2.1.1 | 4.68E-06 | None | None | None | None | N | None | 0 | 3.33E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| A/D | rs537697585 |
-1.714 | 1.0 | D | 0.849 | 0.739 | 0.826406704241 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 6.57E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/D | rs537697585 |
-1.714 | 1.0 | D | 0.849 | 0.739 | 0.826406704241 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 1.4E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| A/D | rs537697585 |
-1.714 | 1.0 | D | 0.849 | 0.739 | 0.826406704241 | gnomAD-4.0.0 | 6.57756E-06 | None | None | None | None | N | None | 0 | 6.5591E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/S | rs730880239 |
None | 1.0 | D | 0.581 | 0.672 | 0.670494219762 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/T | rs730880239 |
-1.436 | 1.0 | D | 0.707 | 0.609 | None | gnomAD-2.1.1 | 1.59578E-04 | None | None | None | None | N | None | 0 | 1.29862E-04 | None | 0 | 5.34E-05 | None | 0 | None | 3.96336E-04 | 1.92375E-04 | 4.92287E-04 |
| A/T | rs730880239 |
-1.436 | 1.0 | D | 0.707 | 0.609 | None | gnomAD-3.1.2 | 5.93E-05 | None | None | None | None | N | None | 0 | 6.57E-05 | 0 | 0 | 0 | None | 1.88395E-04 | 0 | 8.84E-05 | 0 | 0 |
| A/T | rs730880239 |
-1.436 | 1.0 | D | 0.707 | 0.609 | None | gnomAD-4.0.0 | 8.24287E-05 | None | None | None | None | N | None | 0 | 9.11677E-05 | None | 0 | 2.25805E-05 | None | 5.4694E-04 | 0 | 7.26984E-05 | 0 | 8.2971E-05 |
| A/V | None | None | 1.0 | D | 0.607 | 0.491 | 0.636647316547 | gnomAD-4.0.0 | 3.53649E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.59574E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.7967 | likely_pathogenic | 0.8701 | pathogenic | -0.935 | Destabilizing | 1.0 | D | 0.762 | deleterious | None | None | None | None | N |
| A/D | 0.9963 | likely_pathogenic | 0.998 | pathogenic | -1.967 | Destabilizing | 1.0 | D | 0.849 | deleterious | D | 0.696535458 | None | None | N |
| A/E | 0.9933 | likely_pathogenic | 0.9957 | pathogenic | -1.81 | Destabilizing | 1.0 | D | 0.832 | deleterious | None | None | None | None | N |
| A/F | 0.9805 | likely_pathogenic | 0.9882 | pathogenic | -0.768 | Destabilizing | 1.0 | D | 0.866 | deleterious | None | None | None | None | N |
| A/G | 0.5688 | likely_pathogenic | 0.6332 | pathogenic | -1.511 | Destabilizing | 1.0 | D | 0.558 | neutral | D | 0.611673405 | None | None | N |
| A/H | 0.9955 | likely_pathogenic | 0.9977 | pathogenic | -1.926 | Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | N |
| A/I | 0.8933 | likely_pathogenic | 0.9071 | pathogenic | 0.136 | Stabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | None | N |
| A/K | 0.9967 | likely_pathogenic | 0.9983 | pathogenic | -1.36 | Destabilizing | 1.0 | D | 0.833 | deleterious | None | None | None | None | N |
| A/L | 0.8743 | likely_pathogenic | 0.907 | pathogenic | 0.136 | Stabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | N |
| A/M | 0.9171 | likely_pathogenic | 0.9437 | pathogenic | 0.091 | Stabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | N |
| A/N | 0.9908 | likely_pathogenic | 0.9951 | pathogenic | -1.467 | Destabilizing | 1.0 | D | 0.856 | deleterious | None | None | None | None | N |
| A/P | 0.9966 | likely_pathogenic | 0.9978 | pathogenic | -0.216 | Destabilizing | 1.0 | D | 0.853 | deleterious | D | 0.733313325 | None | None | N |
| A/Q | 0.9885 | likely_pathogenic | 0.993 | pathogenic | -1.337 | Destabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | None | N |
| A/R | 0.9889 | likely_pathogenic | 0.9928 | pathogenic | -1.339 | Destabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | None | N |
| A/S | 0.5366 | ambiguous | 0.6162 | pathogenic | -1.897 | Destabilizing | 1.0 | D | 0.581 | neutral | D | 0.696709598 | None | None | N |
| A/T | 0.6177 | likely_pathogenic | 0.711 | pathogenic | -1.612 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | D | 0.579428069 | None | None | N |
| A/V | 0.5799 | likely_pathogenic | 0.6389 | pathogenic | -0.216 | Destabilizing | 1.0 | D | 0.607 | neutral | D | 0.52332919 | None | None | N |
| A/W | 0.9991 | likely_pathogenic | 0.9995 | pathogenic | -1.492 | Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | N |
| A/Y | 0.9939 | likely_pathogenic | 0.9967 | pathogenic | -0.921 | Destabilizing | 1.0 | D | 0.871 | deleterious | 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.