Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17393 | 52402;52403;52404 | chr2:178608834;178608833;178608832 | chr2:179473561;179473560;179473559 |
| N2AB | 15752 | 47479;47480;47481 | chr2:178608834;178608833;178608832 | chr2:179473561;179473560;179473559 |
| N2A | 14825 | 44698;44699;44700 | chr2:178608834;178608833;178608832 | chr2:179473561;179473560;179473559 |
| N2B | 8328 | 25207;25208;25209 | chr2:178608834;178608833;178608832 | chr2:179473561;179473560;179473559 |
| Novex-1 | 8453 | 25582;25583;25584 | chr2:178608834;178608833;178608832 | chr2:179473561;179473560;179473559 |
| Novex-2 | 8520 | 25783;25784;25785 | chr2:178608834;178608833;178608832 | chr2:179473561;179473560;179473559 |
| 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 | rs1470469789  |
None | 1.0 | D | 0.89 | 0.706 | 0.723066985631 | gnomAD-4.0.0 | 1.59431E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.02902E-05 |
| P/S | rs1481856511 |
None | 1.0 | N | 0.844 | 0.611 | 0.424194796918 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| P/S | rs1481856511 |
None | 1.0 | N | 0.844 | 0.611 | 0.424194796918 | gnomAD-4.0.0 | 6.58198E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47236E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.9347 | likely_pathogenic | 0.9444 | pathogenic | -2.02 | Highly Destabilizing | 1.0 | D | 0.819 | deleterious | D | 0.526693324 | None | None | I |
| P/C | 0.9893 | likely_pathogenic | 0.9917 | pathogenic | -1.389 | Destabilizing | 1.0 | D | 0.848 | deleterious | None | None | None | None | I |
| P/D | 0.9989 | likely_pathogenic | 0.9993 | pathogenic | -2.557 | Highly Destabilizing | 1.0 | D | 0.839 | deleterious | None | None | None | None | I |
| P/E | 0.9975 | likely_pathogenic | 0.9982 | pathogenic | -2.425 | Highly Destabilizing | 1.0 | D | 0.84 | deleterious | None | None | None | None | I |
| P/F | 0.9996 | likely_pathogenic | 0.9997 | pathogenic | -1.338 | Destabilizing | 1.0 | D | 0.87 | deleterious | None | None | None | None | I |
| P/G | 0.9933 | likely_pathogenic | 0.9948 | pathogenic | -2.482 | Highly Destabilizing | 1.0 | D | 0.884 | deleterious | None | None | None | None | I |
| P/H | 0.9968 | likely_pathogenic | 0.9978 | pathogenic | -2.262 | Highly Destabilizing | 1.0 | D | 0.861 | deleterious | D | 0.542684439 | None | None | I |
| P/I | 0.996 | likely_pathogenic | 0.9971 | pathogenic | -0.77 | Destabilizing | 1.0 | D | 0.867 | deleterious | None | None | None | None | I |
| P/K | 0.999 | likely_pathogenic | 0.9993 | pathogenic | -1.852 | Destabilizing | 1.0 | D | 0.836 | deleterious | None | None | None | None | I |
| P/L | 0.9836 | likely_pathogenic | 0.9874 | pathogenic | -0.77 | Destabilizing | 1.0 | D | 0.89 | deleterious | D | 0.552430902 | None | None | I |
| P/M | 0.9976 | likely_pathogenic | 0.9982 | pathogenic | -0.577 | Destabilizing | 1.0 | D | 0.855 | deleterious | None | None | None | None | I |
| P/N | 0.9988 | likely_pathogenic | 0.9991 | pathogenic | -1.901 | Destabilizing | 1.0 | D | 0.878 | deleterious | None | None | None | None | I |
| P/Q | 0.9969 | likely_pathogenic | 0.9978 | pathogenic | -1.887 | Destabilizing | 1.0 | D | 0.823 | deleterious | None | None | None | None | I |
| P/R | 0.9959 | likely_pathogenic | 0.9973 | pathogenic | -1.481 | Destabilizing | 1.0 | D | 0.877 | deleterious | D | 0.542430949 | None | None | I |
| P/S | 0.9863 | likely_pathogenic | 0.9893 | pathogenic | -2.437 | Highly Destabilizing | 1.0 | D | 0.844 | deleterious | N | 0.506195986 | None | None | I |
| P/T | 0.9869 | likely_pathogenic | 0.99 | pathogenic | -2.183 | Highly Destabilizing | 1.0 | D | 0.841 | deleterious | D | 0.530567665 | None | None | I |
| P/V | 0.986 | likely_pathogenic | 0.9891 | pathogenic | -1.157 | Destabilizing | 1.0 | D | 0.893 | deleterious | None | None | None | None | I |
| P/W | 0.9998 | likely_pathogenic | 0.9999 | pathogenic | -1.82 | Destabilizing | 1.0 | D | 0.845 | deleterious | None | None | None | None | I |
| P/Y | 0.9995 | likely_pathogenic | 0.9997 | pathogenic | -1.47 | Destabilizing | 1.0 | D | 0.877 | deleterious | None | None | None | None | I |
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.