Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27079 | 81460;81461;81462 | chr2:178564897;178564896;178564895 | chr2:179429624;179429623;179429622 |
| N2AB | 25438 | 76537;76538;76539 | chr2:178564897;178564896;178564895 | chr2:179429624;179429623;179429622 |
| N2A | 24511 | 73756;73757;73758 | chr2:178564897;178564896;178564895 | chr2:179429624;179429623;179429622 |
| N2B | 18014 | 54265;54266;54267 | chr2:178564897;178564896;178564895 | chr2:179429624;179429623;179429622 |
| Novex-1 | 18139 | 54640;54641;54642 | chr2:178564897;178564896;178564895 | chr2:179429624;179429623;179429622 |
| Novex-2 | 18206 | 54841;54842;54843 | chr2:178564897;178564896;178564895 | chr2:179429624;179429623;179429622 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | rs747977338  |
None | 1.0 | N | 0.883 | 0.507 | 0.563619085548 | gnomAD-4.0.0 | 1.5944E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86125E-06 | 0 | 0 |
| P/R | rs747977338 |
-1.038 | 1.0 | D | 0.894 | 0.519 | 0.57106906325 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.31E-05 | None | 0 | 0 | 0 |
| P/R | rs747977338 |
-1.038 | 1.0 | D | 0.894 | 0.519 | 0.57106906325 | gnomAD-4.0.0 | 1.5944E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43922E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.6321 | likely_pathogenic | 0.6035 | pathogenic | -2.08 | Highly Destabilizing | 1.0 | D | 0.825 | deleterious | N | 0.51243914 | None | None | N |
| P/C | 0.9342 | likely_pathogenic | 0.9298 | pathogenic | -1.644 | Destabilizing | 1.0 | D | 0.829 | deleterious | None | None | None | None | N |
| P/D | 0.9995 | likely_pathogenic | 0.9993 | pathogenic | -2.713 | Highly Destabilizing | 1.0 | D | 0.851 | deleterious | None | None | None | None | N |
| P/E | 0.9986 | likely_pathogenic | 0.9983 | pathogenic | -2.45 | Highly Destabilizing | 1.0 | D | 0.85 | deleterious | None | None | None | None | N |
| P/F | 0.9986 | likely_pathogenic | 0.998 | pathogenic | -1.122 | Destabilizing | 1.0 | D | 0.884 | deleterious | None | None | None | None | N |
| P/G | 0.9855 | likely_pathogenic | 0.983 | pathogenic | -2.628 | Highly Destabilizing | 1.0 | D | 0.863 | deleterious | None | None | None | None | N |
| P/H | 0.9973 | likely_pathogenic | 0.9969 | pathogenic | -2.391 | Highly Destabilizing | 1.0 | D | 0.839 | deleterious | D | 0.54538242 | None | None | N |
| P/I | 0.9093 | likely_pathogenic | 0.8906 | pathogenic | -0.522 | Destabilizing | 1.0 | D | 0.9 | deleterious | None | None | None | None | N |
| P/K | 0.999 | likely_pathogenic | 0.9988 | pathogenic | -1.448 | Destabilizing | 1.0 | D | 0.851 | deleterious | None | None | None | None | N |
| P/L | 0.7693 | likely_pathogenic | 0.7288 | pathogenic | -0.522 | Destabilizing | 1.0 | D | 0.883 | deleterious | N | 0.488849204 | None | None | N |
| P/M | 0.9751 | likely_pathogenic | 0.9717 | pathogenic | -0.874 | Destabilizing | 1.0 | D | 0.833 | deleterious | None | None | None | None | N |
| P/N | 0.9973 | likely_pathogenic | 0.9974 | pathogenic | -1.917 | Destabilizing | 1.0 | D | 0.894 | deleterious | None | None | None | None | N |
| P/Q | 0.996 | likely_pathogenic | 0.9954 | pathogenic | -1.674 | Destabilizing | 1.0 | D | 0.862 | deleterious | None | None | None | None | N |
| P/R | 0.9965 | likely_pathogenic | 0.9957 | pathogenic | -1.48 | Destabilizing | 1.0 | D | 0.894 | deleterious | D | 0.54538242 | None | None | N |
| P/S | 0.9658 | likely_pathogenic | 0.9632 | pathogenic | -2.491 | Highly Destabilizing | 1.0 | D | 0.856 | deleterious | D | 0.533772626 | None | None | N |
| P/T | 0.9245 | likely_pathogenic | 0.9191 | pathogenic | -2.082 | Highly Destabilizing | 1.0 | D | 0.849 | deleterious | D | 0.533519136 | None | None | N |
| P/V | 0.7707 | likely_pathogenic | 0.7442 | pathogenic | -1.019 | Destabilizing | 1.0 | D | 0.866 | deleterious | None | None | None | None | N |
| P/W | 0.9998 | likely_pathogenic | 0.9997 | pathogenic | -1.604 | Destabilizing | 1.0 | D | 0.821 | deleterious | None | None | None | None | N |
| P/Y | 0.9993 | likely_pathogenic | 0.9991 | pathogenic | -1.249 | Destabilizing | 1.0 | D | 0.893 | 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.