Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21975 | 66148;66149;66150 | chr2:178582533;178582532;178582531 | chr2:179447260;179447259;179447258 |
| N2AB | 20334 | 61225;61226;61227 | chr2:178582533;178582532;178582531 | chr2:179447260;179447259;179447258 |
| N2A | 19407 | 58444;58445;58446 | chr2:178582533;178582532;178582531 | chr2:179447260;179447259;179447258 |
| N2B | 12910 | 38953;38954;38955 | chr2:178582533;178582532;178582531 | chr2:179447260;179447259;179447258 |
| Novex-1 | 13035 | 39328;39329;39330 | chr2:178582533;178582532;178582531 | chr2:179447260;179447259;179447258 |
| Novex-2 | 13102 | 39529;39530;39531 | chr2:178582533;178582532;178582531 | chr2:179447260;179447259;179447258 |
| 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 | None | None | 1.0 | D | 0.725 | 0.462 | 0.660408421259 | gnomAD-4.0.0 | 6.84602E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99849E-07 | 0 | 0 |
| L/P | rs766511481  |
-1.974 | 1.0 | D | 0.93 | 0.812 | 0.899796760218 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.30881E-04 | None | 0 | 0 | 0 |
| L/P | rs766511481 |
-1.974 | 1.0 | D | 0.93 | 0.812 | 0.899796760218 | gnomAD-4.0.0 | 1.43765E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.32029E-04 | 1.65804E-05 |
| L/V | None | None | 0.999 | N | 0.557 | 0.298 | 0.473774312618 | gnomAD-4.0.0 | 6.84602E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99849E-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 | 0.9671 | likely_pathogenic | 0.9519 | pathogenic | -2.696 | Highly Destabilizing | 0.999 | D | 0.706 | prob.neutral | None | None | None | None | N |
| L/C | 0.9563 | likely_pathogenic | 0.9267 | pathogenic | -2.372 | Highly Destabilizing | 1.0 | D | 0.825 | deleterious | None | None | None | None | N |
| L/D | 0.9996 | likely_pathogenic | 0.9997 | pathogenic | -2.952 | Highly Destabilizing | 1.0 | D | 0.927 | deleterious | None | None | None | None | N |
| L/E | 0.9979 | likely_pathogenic | 0.9976 | pathogenic | -2.65 | Highly Destabilizing | 1.0 | D | 0.907 | deleterious | None | None | None | None | N |
| L/F | 0.6091 | likely_pathogenic | 0.6146 | pathogenic | -1.702 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | D | 0.526417062 | None | None | N |
| L/G | 0.996 | likely_pathogenic | 0.9949 | pathogenic | -3.32 | Highly Destabilizing | 1.0 | D | 0.899 | deleterious | None | None | None | None | N |
| L/H | 0.9954 | likely_pathogenic | 0.9949 | pathogenic | -2.952 | Highly Destabilizing | 1.0 | D | 0.896 | deleterious | D | 0.560285396 | None | None | N |
| L/I | 0.0972 | likely_benign | 0.0908 | benign | -0.849 | Destabilizing | 0.999 | D | 0.541 | neutral | N | 0.48744294 | None | None | N |
| L/K | 0.9965 | likely_pathogenic | 0.9962 | pathogenic | -2.009 | Highly Destabilizing | 1.0 | D | 0.891 | deleterious | None | None | None | None | N |
| L/M | 0.3907 | ambiguous | 0.3586 | ambiguous | -1.12 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | N |
| L/N | 0.9982 | likely_pathogenic | 0.9979 | pathogenic | -2.567 | Highly Destabilizing | 1.0 | D | 0.93 | deleterious | None | None | None | None | N |
| L/P | 0.9956 | likely_pathogenic | 0.9946 | pathogenic | -1.451 | Destabilizing | 1.0 | D | 0.93 | deleterious | D | 0.560285396 | None | None | N |
| L/Q | 0.9939 | likely_pathogenic | 0.9929 | pathogenic | -2.265 | Highly Destabilizing | 1.0 | D | 0.924 | deleterious | None | None | None | None | N |
| L/R | 0.9936 | likely_pathogenic | 0.9925 | pathogenic | -2.009 | Highly Destabilizing | 1.0 | D | 0.905 | deleterious | D | 0.560285396 | None | None | N |
| L/S | 0.9974 | likely_pathogenic | 0.9966 | pathogenic | -3.323 | Highly Destabilizing | 1.0 | D | 0.892 | deleterious | None | None | None | None | N |
| L/T | 0.9822 | likely_pathogenic | 0.9719 | pathogenic | -2.841 | Highly Destabilizing | 1.0 | D | 0.798 | deleterious | None | None | None | None | N |
| L/V | 0.1584 | likely_benign | 0.1214 | benign | -1.451 | Destabilizing | 0.999 | D | 0.557 | neutral | N | 0.513673202 | None | None | N |
| L/W | 0.9806 | likely_pathogenic | 0.9808 | pathogenic | -2.047 | Highly Destabilizing | 1.0 | D | 0.865 | deleterious | None | None | None | None | N |
| L/Y | 0.978 | likely_pathogenic | 0.9776 | pathogenic | -1.793 | Destabilizing | 1.0 | D | 0.824 | 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.