Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23067 | 69424;69425;69426 | chr2:178577136;178577135;178577134 | chr2:179441863;179441862;179441861 |
| N2AB | 21426 | 64501;64502;64503 | chr2:178577136;178577135;178577134 | chr2:179441863;179441862;179441861 |
| N2A | 20499 | 61720;61721;61722 | chr2:178577136;178577135;178577134 | chr2:179441863;179441862;179441861 |
| N2B | 14002 | 42229;42230;42231 | chr2:178577136;178577135;178577134 | chr2:179441863;179441862;179441861 |
| Novex-1 | 14127 | 42604;42605;42606 | chr2:178577136;178577135;178577134 | chr2:179441863;179441862;179441861 |
| Novex-2 | 14194 | 42805;42806;42807 | chr2:178577136;178577135;178577134 | chr2:179441863;179441862;179441861 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/N | None | None | 1.0 | N | 0.711 | 0.381 | 0.449088463789 | gnomAD-4.0.0 | 6.84413E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99651E-07 | 0 | 0 |
| D/Y | rs794729485  |
None | 1.0 | D | 0.631 | 0.523 | 0.847155551282 | 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 |
| D/Y | rs794729485 |
None | 1.0 | D | 0.631 | 0.523 | 0.847155551282 | gnomAD-4.0.0 | 5.5794E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.6302E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.8921 | likely_pathogenic | 0.8565 | pathogenic | -0.381 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | N | 0.492564139 | None | None | I |
| D/C | 0.9849 | likely_pathogenic | 0.9802 | pathogenic | 0.007 | Stabilizing | 1.0 | D | 0.651 | neutral | None | None | None | None | I |
| D/E | 0.8618 | likely_pathogenic | 0.8212 | pathogenic | -0.675 | Destabilizing | 1.0 | D | 0.443 | neutral | N | 0.500766893 | None | None | I |
| D/F | 0.9873 | likely_pathogenic | 0.9839 | pathogenic | -0.51 | Destabilizing | 1.0 | D | 0.648 | neutral | None | None | None | None | I |
| D/G | 0.8701 | likely_pathogenic | 0.8221 | pathogenic | -0.651 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | D | 0.5228873 | None | None | I |
| D/H | 0.9443 | likely_pathogenic | 0.9318 | pathogenic | -0.897 | Destabilizing | 1.0 | D | 0.655 | neutral | N | 0.518012228 | None | None | I |
| D/I | 0.9539 | likely_pathogenic | 0.9402 | pathogenic | 0.299 | Stabilizing | 1.0 | D | 0.682 | prob.neutral | None | None | None | None | I |
| D/K | 0.9734 | likely_pathogenic | 0.9608 | pathogenic | -0.126 | Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | I |
| D/L | 0.9648 | likely_pathogenic | 0.9469 | pathogenic | 0.299 | Stabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | I |
| D/M | 0.9789 | likely_pathogenic | 0.9721 | pathogenic | 0.738 | Stabilizing | 1.0 | D | 0.642 | neutral | None | None | None | None | I |
| D/N | 0.2839 | likely_benign | 0.2158 | benign | -0.379 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | N | 0.509574104 | None | None | I |
| D/P | 0.9872 | likely_pathogenic | 0.9798 | pathogenic | 0.097 | Stabilizing | 1.0 | D | 0.748 | deleterious | None | None | None | None | I |
| D/Q | 0.9645 | likely_pathogenic | 0.9546 | pathogenic | -0.308 | Destabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | I |
| D/R | 0.975 | likely_pathogenic | 0.9694 | pathogenic | -0.172 | Destabilizing | 1.0 | D | 0.705 | prob.neutral | None | None | None | None | I |
| D/S | 0.6899 | likely_pathogenic | 0.6225 | pathogenic | -0.547 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | I |
| D/T | 0.8083 | likely_pathogenic | 0.7221 | pathogenic | -0.334 | Destabilizing | 1.0 | D | 0.758 | deleterious | None | None | None | None | I |
| D/V | 0.9012 | likely_pathogenic | 0.8693 | pathogenic | 0.097 | Stabilizing | 1.0 | D | 0.703 | prob.neutral | D | 0.527051129 | None | None | I |
| D/W | 0.9966 | likely_pathogenic | 0.9966 | pathogenic | -0.479 | Destabilizing | 1.0 | D | 0.649 | neutral | None | None | None | None | I |
| D/Y | 0.8995 | likely_pathogenic | 0.8828 | pathogenic | -0.308 | Destabilizing | 1.0 | D | 0.631 | neutral | D | 0.554816623 | 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.