Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3114 | 9565;9566;9567 | chr2:178767890;178767889;178767888 | chr2:179632617;179632616;179632615 |
| N2AB | 3114 | 9565;9566;9567 | chr2:178767890;178767889;178767888 | chr2:179632617;179632616;179632615 |
| N2A | 3114 | 9565;9566;9567 | chr2:178767890;178767889;178767888 | chr2:179632617;179632616;179632615 |
| N2B | 3068 | 9427;9428;9429 | chr2:178767890;178767889;178767888 | chr2:179632617;179632616;179632615 |
| Novex-1 | 3068 | 9427;9428;9429 | chr2:178767890;178767889;178767888 | chr2:179632617;179632616;179632615 |
| Novex-2 | 3068 | 9427;9428;9429 | chr2:178767890;178767889;178767888 | chr2:179632617;179632616;179632615 |
| Novex-3 | 3114 | 9565;9566;9567 | chr2:178767890;178767889;178767888 | chr2:179632617;179632616;179632615 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/F | rs556868685  |
-1.436 | 0.993 | D | 0.799 | 0.417 | 0.347217280506 | gnomAD-2.1.1 | 7.97E-06 | None | None | None | None | N | None | 6.15E-05 | 2.89E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| L/F | rs556868685 |
-1.436 | 0.993 | D | 0.799 | 0.417 | 0.347217280506 | 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 |
| L/F | rs556868685 |
-1.436 | 0.993 | D | 0.799 | 0.417 | 0.347217280506 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| L/F | rs556868685 |
-1.436 | 0.993 | D | 0.799 | 0.417 | 0.347217280506 | gnomAD-4.0.0 | 3.09766E-06 | None | None | None | None | N | None | 1.33223E-05 | 1.66628E-05 | None | 0 | 0 | None | 0 | 0 | 2.54237E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.9726 | likely_pathogenic | 0.9778 | pathogenic | -1.861 | Destabilizing | 0.983 | D | 0.773 | deleterious | None | None | None | None | N |
| L/C | 0.9403 | likely_pathogenic | 0.9582 | pathogenic | -1.195 | Destabilizing | 1.0 | D | 0.852 | deleterious | None | None | None | None | N |
| L/D | 0.9999 | likely_pathogenic | 0.9999 | pathogenic | -2.726 | Highly Destabilizing | 0.999 | D | 0.924 | deleterious | None | None | None | None | N |
| L/E | 0.9988 | likely_pathogenic | 0.999 | pathogenic | -2.433 | Highly Destabilizing | 0.998 | D | 0.901 | deleterious | None | None | None | None | N |
| L/F | 0.7569 | likely_pathogenic | 0.8309 | pathogenic | -1.229 | Destabilizing | 0.993 | D | 0.799 | deleterious | D | 0.566712159 | None | None | N |
| L/G | 0.9958 | likely_pathogenic | 0.9968 | pathogenic | -2.385 | Highly Destabilizing | 0.998 | D | 0.892 | deleterious | None | None | None | None | N |
| L/H | 0.9949 | likely_pathogenic | 0.9965 | pathogenic | -2.388 | Highly Destabilizing | 1.0 | D | 0.908 | deleterious | D | 0.655582391 | None | None | N |
| L/I | 0.3635 | ambiguous | 0.3993 | ambiguous | -0.29 | Destabilizing | 0.955 | D | 0.699 | prob.neutral | N | 0.51156094 | None | None | N |
| L/K | 0.997 | likely_pathogenic | 0.9974 | pathogenic | -1.441 | Destabilizing | 0.998 | D | 0.899 | deleterious | None | None | None | None | N |
| L/M | 0.4532 | ambiguous | 0.5044 | ambiguous | -0.53 | Destabilizing | 0.921 | D | 0.615 | neutral | None | None | None | None | N |
| L/N | 0.9986 | likely_pathogenic | 0.9989 | pathogenic | -2.16 | Highly Destabilizing | 0.999 | D | 0.922 | deleterious | None | None | None | None | N |
| L/P | 0.9992 | likely_pathogenic | 0.9992 | pathogenic | -0.805 | Destabilizing | 0.999 | D | 0.919 | deleterious | D | 0.655582391 | None | None | N |
| L/Q | 0.9929 | likely_pathogenic | 0.9944 | pathogenic | -1.757 | Destabilizing | 0.998 | D | 0.917 | deleterious | None | None | None | None | N |
| L/R | 0.9938 | likely_pathogenic | 0.9948 | pathogenic | -1.798 | Destabilizing | 0.997 | D | 0.899 | deleterious | D | 0.655582391 | None | None | N |
| L/S | 0.9979 | likely_pathogenic | 0.9985 | pathogenic | -2.56 | Highly Destabilizing | 0.998 | D | 0.894 | deleterious | None | None | None | None | N |
| L/T | 0.993 | likely_pathogenic | 0.9947 | pathogenic | -2.108 | Highly Destabilizing | 0.995 | D | 0.808 | deleterious | None | None | None | None | N |
| L/V | 0.4935 | ambiguous | 0.5238 | ambiguous | -0.805 | Destabilizing | 0.955 | D | 0.713 | prob.delet. | D | 0.569636723 | None | None | N |
| L/W | 0.9825 | likely_pathogenic | 0.9885 | pathogenic | -1.601 | Destabilizing | 1.0 | D | 0.886 | deleterious | None | None | None | None | N |
| L/Y | 0.9794 | likely_pathogenic | 0.9869 | pathogenic | -1.327 | Destabilizing | 0.998 | D | 0.853 | 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.