Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27093 | 81502;81503;81504 | chr2:178564855;178564854;178564853 | chr2:179429582;179429581;179429580 |
| N2AB | 25452 | 76579;76580;76581 | chr2:178564855;178564854;178564853 | chr2:179429582;179429581;179429580 |
| N2A | 24525 | 73798;73799;73800 | chr2:178564855;178564854;178564853 | chr2:179429582;179429581;179429580 |
| N2B | 18028 | 54307;54308;54309 | chr2:178564855;178564854;178564853 | chr2:179429582;179429581;179429580 |
| Novex-1 | 18153 | 54682;54683;54684 | chr2:178564855;178564854;178564853 | chr2:179429582;179429581;179429580 |
| Novex-2 | 18220 | 54883;54884;54885 | chr2:178564855;178564854;178564853 | chr2:179429582;179429581;179429580 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| W/C | None | None | 0.056 | D | 0.744 | 0.806 | 0.842507524372 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 6.07533E-05 | 0 |
| W/L | rs758518537  |
-2.815 | 0.805 | D | 0.843 | 0.705 | 0.940321820105 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.28E-05 | None | 0 | 0 | 0 |
| W/L | rs758518537 |
-2.815 | 0.805 | D | 0.843 | 0.705 | 0.940321820105 | gnomAD-4.0.0 | 1.59282E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43538E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| W/A | 0.9986 | likely_pathogenic | 0.9987 | pathogenic | -3.952 | Highly Destabilizing | 0.845 | D | 0.87 | deleterious | None | None | None | None | N |
| W/C | 0.9986 | likely_pathogenic | 0.9987 | pathogenic | -2.03 | Highly Destabilizing | 0.056 | N | 0.744 | deleterious | D | 0.672060828 | None | None | N |
| W/D | 0.9998 | likely_pathogenic | 0.9998 | pathogenic | -3.981 | Highly Destabilizing | 0.996 | D | 0.895 | deleterious | None | None | None | None | N |
| W/E | 0.9998 | likely_pathogenic | 0.9998 | pathogenic | -3.884 | Highly Destabilizing | 0.996 | D | 0.897 | deleterious | None | None | None | None | N |
| W/F | 0.8352 | likely_pathogenic | 0.853 | pathogenic | -2.816 | Highly Destabilizing | 0.987 | D | 0.795 | deleterious | None | None | None | None | N |
| W/G | 0.9881 | likely_pathogenic | 0.9887 | pathogenic | -4.141 | Highly Destabilizing | 0.983 | D | 0.851 | deleterious | D | 0.672060828 | None | None | N |
| W/H | 0.9982 | likely_pathogenic | 0.9983 | pathogenic | -3.228 | Highly Destabilizing | 0.999 | D | 0.867 | deleterious | None | None | None | None | N |
| W/I | 0.9965 | likely_pathogenic | 0.9969 | pathogenic | -3.173 | Highly Destabilizing | 0.975 | D | 0.898 | deleterious | None | None | None | None | N |
| W/K | 0.9999 | likely_pathogenic | 0.9999 | pathogenic | -3.158 | Highly Destabilizing | 0.987 | D | 0.895 | deleterious | None | None | None | None | N |
| W/L | 0.9909 | likely_pathogenic | 0.9922 | pathogenic | -3.173 | Highly Destabilizing | 0.805 | D | 0.843 | deleterious | D | 0.655032446 | None | None | N |
| W/M | 0.998 | likely_pathogenic | 0.9982 | pathogenic | -2.403 | Highly Destabilizing | 0.999 | D | 0.813 | deleterious | None | None | None | None | N |
| W/N | 0.9997 | likely_pathogenic | 0.9997 | pathogenic | -3.729 | Highly Destabilizing | 0.996 | D | 0.909 | deleterious | None | None | None | None | N |
| W/P | 0.9998 | likely_pathogenic | 0.9998 | pathogenic | -3.465 | Highly Destabilizing | 0.996 | D | 0.908 | deleterious | None | None | None | None | N |
| W/Q | 0.9999 | likely_pathogenic | 0.9999 | pathogenic | -3.632 | Highly Destabilizing | 0.996 | D | 0.892 | deleterious | None | None | None | None | N |
| W/R | 0.9997 | likely_pathogenic | 0.9997 | pathogenic | -2.724 | Highly Destabilizing | 0.994 | D | 0.909 | deleterious | D | 0.672060828 | None | None | N |
| W/S | 0.9974 | likely_pathogenic | 0.9973 | pathogenic | -3.836 | Highly Destabilizing | 0.967 | D | 0.891 | deleterious | D | 0.672060828 | None | None | N |
| W/T | 0.9989 | likely_pathogenic | 0.999 | pathogenic | -3.678 | Highly Destabilizing | 0.975 | D | 0.844 | deleterious | None | None | None | None | N |
| W/V | 0.9973 | likely_pathogenic | 0.9975 | pathogenic | -3.465 | Highly Destabilizing | 0.975 | D | 0.888 | deleterious | None | None | None | None | N |
| W/Y | 0.9612 | likely_pathogenic | 0.9646 | pathogenic | -2.741 | Highly Destabilizing | 0.996 | D | 0.791 | 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.