Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24698 | 74317;74318;74319 | chr2:178572040;178572039;178572038 | chr2:179436767;179436766;179436765 |
| N2AB | 23057 | 69394;69395;69396 | chr2:178572040;178572039;178572038 | chr2:179436767;179436766;179436765 |
| N2A | 22130 | 66613;66614;66615 | chr2:178572040;178572039;178572038 | chr2:179436767;179436766;179436765 |
| N2B | 15633 | 47122;47123;47124 | chr2:178572040;178572039;178572038 | chr2:179436767;179436766;179436765 |
| Novex-1 | 15758 | 47497;47498;47499 | chr2:178572040;178572039;178572038 | chr2:179436767;179436766;179436765 |
| Novex-2 | 15825 | 47698;47699;47700 | chr2:178572040;178572039;178572038 | chr2:179436767;179436766;179436765 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/I | rs769515743  |
-0.117 | 1.0 | D | 0.911 | 0.525 | 0.782365095754 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| S/I | rs769515743 |
-0.117 | 1.0 | D | 0.911 | 0.525 | 0.782365095754 | gnomAD-4.0.0 | 3.18486E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.71935E-06 | 0 | 0 |
| S/N | rs769515743 |
-1.4 | 0.998 | D | 0.733 | 0.417 | 0.330331372229 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| S/N | rs769515743 |
-1.4 | 0.998 | D | 0.733 | 0.417 | 0.330331372229 | gnomAD-4.0.0 | 1.59243E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85968E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.701 | likely_pathogenic | 0.689 | pathogenic | -0.739 | Destabilizing | 0.998 | D | 0.721 | prob.delet. | None | None | None | None | N |
| S/C | 0.8913 | likely_pathogenic | 0.8987 | pathogenic | -0.794 | Destabilizing | 1.0 | D | 0.867 | deleterious | D | 0.544016522 | None | None | N |
| S/D | 0.9961 | likely_pathogenic | 0.996 | pathogenic | -1.45 | Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | N |
| S/E | 0.9985 | likely_pathogenic | 0.9984 | pathogenic | -1.376 | Destabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | N |
| S/F | 0.9984 | likely_pathogenic | 0.9983 | pathogenic | -0.692 | Destabilizing | 1.0 | D | 0.917 | deleterious | None | None | None | None | N |
| S/G | 0.3692 | ambiguous | 0.3371 | benign | -1.041 | Destabilizing | 1.0 | D | 0.741 | deleterious | N | 0.455227039 | None | None | N |
| S/H | 0.9962 | likely_pathogenic | 0.9962 | pathogenic | -1.439 | Destabilizing | 1.0 | D | 0.873 | deleterious | None | None | None | None | N |
| S/I | 0.9979 | likely_pathogenic | 0.9974 | pathogenic | -0.02 | Destabilizing | 1.0 | D | 0.911 | deleterious | D | 0.543763032 | None | None | N |
| S/K | 0.9997 | likely_pathogenic | 0.9996 | pathogenic | -0.843 | Destabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | N |
| S/L | 0.9874 | likely_pathogenic | 0.9853 | pathogenic | -0.02 | Destabilizing | 1.0 | D | 0.861 | deleterious | None | None | None | None | N |
| S/M | 0.9939 | likely_pathogenic | 0.9926 | pathogenic | 0.131 | Stabilizing | 1.0 | D | 0.87 | deleterious | None | None | None | None | N |
| S/N | 0.989 | likely_pathogenic | 0.9881 | pathogenic | -1.16 | Destabilizing | 0.998 | D | 0.733 | prob.delet. | D | 0.543002564 | None | None | N |
| S/P | 0.998 | likely_pathogenic | 0.9975 | pathogenic | -0.226 | Destabilizing | 1.0 | D | 0.859 | deleterious | None | None | None | None | N |
| S/Q | 0.9975 | likely_pathogenic | 0.9974 | pathogenic | -1.238 | Destabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | None | N |
| S/R | 0.999 | likely_pathogenic | 0.9989 | pathogenic | -0.796 | Destabilizing | 1.0 | D | 0.865 | deleterious | D | 0.531899748 | None | None | N |
| S/T | 0.9113 | likely_pathogenic | 0.8986 | pathogenic | -0.96 | Destabilizing | 0.988 | D | 0.729 | prob.delet. | D | 0.541988606 | None | None | N |
| S/V | 0.997 | likely_pathogenic | 0.9964 | pathogenic | -0.226 | Destabilizing | 1.0 | D | 0.887 | deleterious | None | None | None | None | N |
| S/W | 0.9977 | likely_pathogenic | 0.9974 | pathogenic | -0.8 | Destabilizing | 1.0 | D | 0.917 | deleterious | None | None | None | None | N |
| S/Y | 0.997 | likely_pathogenic | 0.9965 | pathogenic | -0.463 | Destabilizing | 1.0 | D | 0.921 | 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.