Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21246 | 63961;63962;63963 | chr2:178587573;178587572;178587571 | chr2:179452300;179452299;179452298 |
| N2AB | 19605 | 59038;59039;59040 | chr2:178587573;178587572;178587571 | chr2:179452300;179452299;179452298 |
| N2A | 18678 | 56257;56258;56259 | chr2:178587573;178587572;178587571 | chr2:179452300;179452299;179452298 |
| N2B | 12181 | 36766;36767;36768 | chr2:178587573;178587572;178587571 | chr2:179452300;179452299;179452298 |
| Novex-1 | 12306 | 37141;37142;37143 | chr2:178587573;178587572;178587571 | chr2:179452300;179452299;179452298 |
| Novex-2 | 12373 | 37342;37343;37344 | chr2:178587573;178587572;178587571 | chr2:179452300;179452299;179452298 |
| 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 | rs2049306666  |
None | 1.0 | N | 0.859 | 0.375 | 0.562428738172 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| L/F | rs2049306666 |
None | 1.0 | N | 0.859 | 0.375 | 0.562428738172 | gnomAD-4.0.0 | 6.57903E-06 | None | None | None | None | N | None | 0 | 6.55652E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| L/V | None | None | 0.999 | N | 0.713 | 0.193 | 0.418964662724 | gnomAD-4.0.0 | 1.59435E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86208E-06 | 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 | 0.9441 | likely_pathogenic | 0.9456 | pathogenic | -2.153 | Highly Destabilizing | 0.999 | D | 0.798 | deleterious | None | None | None | None | N |
| L/C | 0.8588 | likely_pathogenic | 0.8736 | pathogenic | -1.629 | Destabilizing | 1.0 | D | 0.866 | deleterious | None | None | None | None | N |
| L/D | 0.9997 | likely_pathogenic | 0.9996 | pathogenic | -1.882 | Destabilizing | 1.0 | D | 0.913 | deleterious | None | None | None | None | N |
| L/E | 0.9973 | likely_pathogenic | 0.9969 | pathogenic | -1.7 | Destabilizing | 1.0 | D | 0.899 | deleterious | None | None | None | None | N |
| L/F | 0.6834 | likely_pathogenic | 0.6957 | pathogenic | -1.3 | Destabilizing | 1.0 | D | 0.859 | deleterious | N | 0.483355476 | None | None | N |
| L/G | 0.9924 | likely_pathogenic | 0.992 | pathogenic | -2.666 | Highly Destabilizing | 1.0 | D | 0.887 | deleterious | None | None | None | None | N |
| L/H | 0.993 | likely_pathogenic | 0.9924 | pathogenic | -2.082 | Highly Destabilizing | 1.0 | D | 0.889 | deleterious | None | None | None | None | N |
| L/I | 0.1972 | likely_benign | 0.2109 | benign | -0.707 | Destabilizing | 0.999 | D | 0.688 | prob.neutral | N | 0.471753929 | None | None | N |
| L/K | 0.9944 | likely_pathogenic | 0.9934 | pathogenic | -1.43 | Destabilizing | 1.0 | D | 0.905 | deleterious | None | None | None | None | N |
| L/M | 0.2792 | likely_benign | 0.3035 | benign | -0.763 | Destabilizing | 1.0 | D | 0.811 | deleterious | None | None | None | None | N |
| L/N | 0.9973 | likely_pathogenic | 0.997 | pathogenic | -1.618 | Destabilizing | 1.0 | D | 0.915 | deleterious | None | None | None | None | N |
| L/P | 0.9973 | likely_pathogenic | 0.9971 | pathogenic | -1.165 | Destabilizing | 1.0 | D | 0.914 | deleterious | None | None | None | None | N |
| L/Q | 0.9852 | likely_pathogenic | 0.9837 | pathogenic | -1.531 | Destabilizing | 1.0 | D | 0.919 | deleterious | None | None | None | None | N |
| L/R | 0.9885 | likely_pathogenic | 0.9866 | pathogenic | -1.187 | Destabilizing | 1.0 | D | 0.913 | deleterious | None | None | None | None | N |
| L/S | 0.9941 | likely_pathogenic | 0.9942 | pathogenic | -2.404 | Highly Destabilizing | 1.0 | D | 0.906 | deleterious | N | 0.511374459 | None | None | N |
| L/T | 0.9762 | likely_pathogenic | 0.9777 | pathogenic | -2.07 | Highly Destabilizing | 1.0 | D | 0.87 | deleterious | None | None | None | None | N |
| L/V | 0.2221 | likely_benign | 0.2533 | benign | -1.165 | Destabilizing | 0.999 | D | 0.713 | prob.delet. | N | 0.473215367 | None | None | N |
| L/W | 0.979 | likely_pathogenic | 0.9781 | pathogenic | -1.579 | Destabilizing | 1.0 | D | 0.872 | deleterious | None | None | None | None | N |
| L/Y | 0.9762 | likely_pathogenic | 0.9765 | pathogenic | -1.273 | Destabilizing | 1.0 | D | 0.887 | 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.