Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20928 | 63007;63008;63009 | chr2:178588943;178588942;178588941 | chr2:179453670;179453669;179453668 |
| N2AB | 19287 | 58084;58085;58086 | chr2:178588943;178588942;178588941 | chr2:179453670;179453669;179453668 |
| N2A | 18360 | 55303;55304;55305 | chr2:178588943;178588942;178588941 | chr2:179453670;179453669;179453668 |
| N2B | 11863 | 35812;35813;35814 | chr2:178588943;178588942;178588941 | chr2:179453670;179453669;179453668 |
| Novex-1 | 11988 | 36187;36188;36189 | chr2:178588943;178588942;178588941 | chr2:179453670;179453669;179453668 |
| Novex-2 | 12055 | 36388;36389;36390 | chr2:178588943;178588942;178588941 | chr2:179453670;179453669;179453668 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/F | rs763157400  |
-2.008 | 1.0 | D | 0.874 | 0.619 | 0.889711523711 | gnomAD-2.1.1 | 8.09E-06 | None | None | None | None | N | None | 0 | 5.83E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| L/F | rs763157400 |
-2.008 | 1.0 | D | 0.874 | 0.619 | 0.889711523711 | gnomAD-4.0.0 | 3.18708E-06 | None | None | None | None | N | None | 0 | 4.58274E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| L/P | None | None | 1.0 | D | 0.858 | 0.853 | 0.952664292917 | gnomAD-4.0.0 | 1.36925E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.53485E-05 | None | 0 | 0 | 8.99716E-07 | 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 | 0.9909 | likely_pathogenic | 0.9924 | pathogenic | -2.639 | Highly Destabilizing | 0.999 | D | 0.833 | deleterious | None | None | None | None | N |
| L/C | 0.9799 | likely_pathogenic | 0.9847 | pathogenic | -2.114 | Highly Destabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | N |
| L/D | 0.9997 | likely_pathogenic | 0.9998 | pathogenic | -2.787 | Highly Destabilizing | 1.0 | D | 0.863 | deleterious | None | None | None | None | N |
| L/E | 0.9988 | likely_pathogenic | 0.9991 | pathogenic | -2.639 | Highly Destabilizing | 1.0 | D | 0.855 | deleterious | None | None | None | None | N |
| L/F | 0.8702 | likely_pathogenic | 0.9301 | pathogenic | -1.785 | Destabilizing | 1.0 | D | 0.874 | deleterious | D | 0.65592182 | None | None | N |
| L/G | 0.9975 | likely_pathogenic | 0.9979 | pathogenic | -3.125 | Highly Destabilizing | 1.0 | D | 0.843 | deleterious | None | None | None | None | N |
| L/H | 0.9965 | likely_pathogenic | 0.9976 | pathogenic | -2.388 | Highly Destabilizing | 1.0 | D | 0.813 | deleterious | D | 0.656729037 | None | None | N |
| L/I | 0.4411 | ambiguous | 0.5358 | ambiguous | -1.268 | Destabilizing | 0.999 | D | 0.844 | deleterious | D | 0.622874077 | None | None | N |
| L/K | 0.9965 | likely_pathogenic | 0.9973 | pathogenic | -2.008 | Highly Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| L/M | 0.5103 | ambiguous | 0.5887 | pathogenic | -1.171 | Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| L/N | 0.9972 | likely_pathogenic | 0.9978 | pathogenic | -2.192 | Highly Destabilizing | 1.0 | D | 0.867 | deleterious | None | None | None | None | N |
| L/P | 0.9973 | likely_pathogenic | 0.998 | pathogenic | -1.703 | Destabilizing | 1.0 | D | 0.858 | deleterious | D | 0.656729037 | None | None | N |
| L/Q | 0.9945 | likely_pathogenic | 0.9961 | pathogenic | -2.211 | Highly Destabilizing | 1.0 | D | 0.859 | deleterious | None | None | None | None | N |
| L/R | 0.9941 | likely_pathogenic | 0.9957 | pathogenic | -1.492 | Destabilizing | 1.0 | D | 0.851 | deleterious | D | 0.640709676 | None | None | N |
| L/S | 0.9987 | likely_pathogenic | 0.9991 | pathogenic | -2.918 | Highly Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| L/T | 0.9921 | likely_pathogenic | 0.9943 | pathogenic | -2.63 | Highly Destabilizing | 1.0 | D | 0.839 | deleterious | None | None | None | None | N |
| L/V | 0.6277 | likely_pathogenic | 0.723 | pathogenic | -1.703 | Destabilizing | 0.999 | D | 0.853 | deleterious | D | 0.587463608 | None | None | N |
| L/W | 0.99 | likely_pathogenic | 0.9947 | pathogenic | -2.046 | Highly Destabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | N |
| L/Y | 0.991 | likely_pathogenic | 0.9951 | pathogenic | -1.811 | Destabilizing | 1.0 | D | 0.827 | 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.