Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22235 | 66928;66929;66930 | chr2:178581565;178581564;178581563 | chr2:179446292;179446291;179446290 |
| N2AB | 20594 | 62005;62006;62007 | chr2:178581565;178581564;178581563 | chr2:179446292;179446291;179446290 |
| N2A | 19667 | 59224;59225;59226 | chr2:178581565;178581564;178581563 | chr2:179446292;179446291;179446290 |
| N2B | 13170 | 39733;39734;39735 | chr2:178581565;178581564;178581563 | chr2:179446292;179446291;179446290 |
| Novex-1 | 13295 | 40108;40109;40110 | chr2:178581565;178581564;178581563 | chr2:179446292;179446291;179446290 |
| Novex-2 | 13362 | 40309;40310;40311 | chr2:178581565;178581564;178581563 | chr2:179446292;179446291;179446290 |
| 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/I | rs751354601  |
-1.091 | 0.843 | N | 0.562 | 0.141 | None | gnomAD-2.1.1 | 1.07513E-04 | None | None | None | None | N | None | 2.89591E-04 | 5.67E-05 | None | 0 | 1.03627E-04 | None | 2.29148E-04 | None | 0 | 9.42E-05 | 0 |
| V/I | rs751354601 |
-1.091 | 0.843 | N | 0.562 | 0.141 | None | gnomAD-3.1.2 | 1.11792E-04 | None | None | None | None | N | None | 2.41383E-04 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 8.83E-05 | 0 | 0 |
| V/I | rs751354601 |
-1.091 | 0.843 | N | 0.562 | 0.141 | None | gnomAD-4.0.0 | 9.55174E-05 | None | None | None | None | N | None | 3.07347E-04 | 6.67401E-05 | None | 0 | 6.71321E-05 | None | 0 | 1.64799E-04 | 8.99072E-05 | 1.31862E-04 | 8.01693E-05 |
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 | 0.5627 | ambiguous | 0.554 | ambiguous | -2.025 | Highly Destabilizing | 0.656 | D | 0.555 | neutral | N | 0.488456898 | None | None | N |
| V/C | 0.8538 | likely_pathogenic | 0.8423 | pathogenic | -1.632 | Destabilizing | 0.998 | D | 0.725 | prob.delet. | None | None | None | None | N |
| V/D | 0.9752 | likely_pathogenic | 0.9787 | pathogenic | -2.441 | Highly Destabilizing | 0.942 | D | 0.845 | deleterious | N | 0.508589069 | None | None | N |
| V/E | 0.8661 | likely_pathogenic | 0.8824 | pathogenic | -2.258 | Highly Destabilizing | 0.915 | D | 0.747 | deleterious | None | None | None | None | N |
| V/F | 0.5401 | ambiguous | 0.4889 | ambiguous | -1.227 | Destabilizing | 0.976 | D | 0.74 | deleterious | N | 0.501396593 | None | None | N |
| V/G | 0.8068 | likely_pathogenic | 0.8201 | pathogenic | -2.508 | Highly Destabilizing | 0.942 | D | 0.805 | deleterious | N | 0.513766856 | None | None | N |
| V/H | 0.9548 | likely_pathogenic | 0.9534 | pathogenic | -2.145 | Highly Destabilizing | 0.994 | D | 0.831 | deleterious | None | None | None | None | N |
| V/I | 0.1092 | likely_benign | 0.1045 | benign | -0.692 | Destabilizing | 0.843 | D | 0.562 | neutral | N | 0.481238283 | None | None | N |
| V/K | 0.8557 | likely_pathogenic | 0.8802 | pathogenic | -1.508 | Destabilizing | 0.915 | D | 0.748 | deleterious | None | None | None | None | N |
| V/L | 0.4685 | ambiguous | 0.4735 | ambiguous | -0.692 | Destabilizing | 0.035 | N | 0.285 | neutral | N | 0.472768499 | None | None | N |
| V/M | 0.3557 | ambiguous | 0.3255 | benign | -0.84 | Destabilizing | 0.956 | D | 0.63 | neutral | None | None | None | None | N |
| V/N | 0.9174 | likely_pathogenic | 0.9156 | pathogenic | -1.751 | Destabilizing | 0.956 | D | 0.855 | deleterious | None | None | None | None | N |
| V/P | 0.9963 | likely_pathogenic | 0.9972 | pathogenic | -1.11 | Destabilizing | 0.978 | D | 0.776 | deleterious | None | None | None | None | N |
| V/Q | 0.7677 | likely_pathogenic | 0.7789 | pathogenic | -1.663 | Destabilizing | 0.16 | N | 0.558 | neutral | None | None | None | None | N |
| V/R | 0.8141 | likely_pathogenic | 0.8455 | pathogenic | -1.298 | Destabilizing | 0.915 | D | 0.84 | deleterious | None | None | None | None | N |
| V/S | 0.7685 | likely_pathogenic | 0.7534 | pathogenic | -2.374 | Highly Destabilizing | 0.956 | D | 0.747 | deleterious | None | None | None | None | N |
| V/T | 0.6047 | likely_pathogenic | 0.546 | ambiguous | -2.06 | Highly Destabilizing | 0.86 | D | 0.575 | neutral | None | None | None | None | N |
| V/W | 0.9762 | likely_pathogenic | 0.976 | pathogenic | -1.659 | Destabilizing | 0.998 | D | 0.817 | deleterious | None | None | None | None | N |
| V/Y | 0.8896 | likely_pathogenic | 0.8803 | pathogenic | -1.31 | Destabilizing | 0.993 | D | 0.739 | prob.delet. | 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.