Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23428 | 70507;70508;70509 | chr2:178575850;178575849;178575848 | chr2:179440577;179440576;179440575 |
| N2AB | 21787 | 65584;65585;65586 | chr2:178575850;178575849;178575848 | chr2:179440577;179440576;179440575 |
| N2A | 20860 | 62803;62804;62805 | chr2:178575850;178575849;178575848 | chr2:179440577;179440576;179440575 |
| N2B | 14363 | 43312;43313;43314 | chr2:178575850;178575849;178575848 | chr2:179440577;179440576;179440575 |
| Novex-1 | 14488 | 43687;43688;43689 | chr2:178575850;178575849;178575848 | chr2:179440577;179440576;179440575 |
| Novex-2 | 14555 | 43888;43889;43890 | chr2:178575850;178575849;178575848 | chr2:179440577;179440576;179440575 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/L | rs794729486  |
0.083 | 0.981 | N | 0.524 | 0.242 | 0.606186980318 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-05 | 0 |
| V/L | rs794729486 |
0.083 | 0.981 | N | 0.524 | 0.242 | 0.606186980318 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| V/L | rs794729486 |
0.083 | 0.981 | N | 0.524 | 0.242 | 0.606186980318 | gnomAD-4.0.0 | 3.04504E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.61492E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.8903 | likely_pathogenic | 0.8803 | pathogenic | -1.803 | Destabilizing | 0.998 | D | 0.517 | neutral | N | 0.51019854 | None | None | I |
| V/C | 0.9189 | likely_pathogenic | 0.9016 | pathogenic | -1.311 | Destabilizing | 1.0 | D | 0.821 | deleterious | None | None | None | None | I |
| V/D | 0.9985 | likely_pathogenic | 0.9987 | pathogenic | -2.265 | Highly Destabilizing | 1.0 | D | 0.894 | deleterious | None | None | None | None | I |
| V/E | 0.9955 | likely_pathogenic | 0.9956 | pathogenic | -1.946 | Destabilizing | 1.0 | D | 0.849 | deleterious | N | 0.492243831 | None | None | I |
| V/F | 0.8679 | likely_pathogenic | 0.8633 | pathogenic | -0.917 | Destabilizing | 1.0 | D | 0.838 | deleterious | None | None | None | None | I |
| V/G | 0.9523 | likely_pathogenic | 0.9523 | pathogenic | -2.435 | Highly Destabilizing | 1.0 | D | 0.868 | deleterious | N | 0.510183502 | None | None | I |
| V/H | 0.9972 | likely_pathogenic | 0.9972 | pathogenic | -2.332 | Highly Destabilizing | 1.0 | D | 0.887 | deleterious | None | None | None | None | I |
| V/I | 0.1247 | likely_benign | 0.1185 | benign | 0.009 | Stabilizing | 0.813 | D | 0.317 | neutral | None | None | None | None | I |
| V/K | 0.9957 | likely_pathogenic | 0.9959 | pathogenic | -1.373 | Destabilizing | 1.0 | D | 0.854 | deleterious | None | None | None | None | I |
| V/L | 0.7636 | likely_pathogenic | 0.7347 | pathogenic | 0.009 | Stabilizing | 0.981 | D | 0.524 | neutral | N | 0.484014803 | None | None | I |
| V/M | 0.8307 | likely_pathogenic | 0.8069 | pathogenic | -0.228 | Destabilizing | 0.999 | D | 0.758 | deleterious | N | 0.491736852 | None | None | I |
| V/N | 0.9936 | likely_pathogenic | 0.994 | pathogenic | -1.965 | Destabilizing | 1.0 | D | 0.905 | deleterious | None | None | None | None | I |
| V/P | 0.9959 | likely_pathogenic | 0.9959 | pathogenic | -0.571 | Destabilizing | 1.0 | D | 0.875 | deleterious | None | None | None | None | I |
| V/Q | 0.9907 | likely_pathogenic | 0.9901 | pathogenic | -1.575 | Destabilizing | 1.0 | D | 0.88 | deleterious | None | None | None | None | I |
| V/R | 0.9874 | likely_pathogenic | 0.9882 | pathogenic | -1.637 | Destabilizing | 1.0 | D | 0.901 | deleterious | None | None | None | None | I |
| V/S | 0.9625 | likely_pathogenic | 0.9637 | pathogenic | -2.608 | Highly Destabilizing | 1.0 | D | 0.858 | deleterious | None | None | None | None | I |
| V/T | 0.8977 | likely_pathogenic | 0.9023 | pathogenic | -2.105 | Highly Destabilizing | 0.998 | D | 0.651 | neutral | None | None | None | None | I |
| V/W | 0.9972 | likely_pathogenic | 0.9973 | pathogenic | -1.423 | Destabilizing | 1.0 | D | 0.875 | deleterious | None | None | None | None | I |
| V/Y | 0.9898 | likely_pathogenic | 0.9902 | pathogenic | -1.009 | Destabilizing | 1.0 | D | 0.849 | 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.