Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 6321 | 19186;19187;19188 | chr2:178729077;178729076;178729075 | chr2:179593804;179593803;179593802 |
| N2AB | 6004 | 18235;18236;18237 | chr2:178729077;178729076;178729075 | chr2:179593804;179593803;179593802 |
| N2A | 5077 | 15454;15455;15456 | chr2:178729077;178729076;178729075 | chr2:179593804;179593803;179593802 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/V | rs145204073  |
-1.487 | 0.041 | N | 0.39 | 0.125 | None | gnomAD-2.1.1 | 4.95336E-04 | None | None | None | None | I | None | 5.38218E-03 | 1.7136E-04 | None | 0 | 0 | None | 0 | None | 0 | 7.95E-06 | 1.42248E-04 |
| I/V | rs145204073 |
-1.487 | 0.041 | N | 0.39 | 0.125 | None | gnomAD-3.1.2 | 1.42064E-03 | None | None | None | None | I | None | 5.04514E-03 | 3.27869E-04 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 2.07469E-04 | 0 |
| I/V | rs145204073 |
-1.487 | 0.041 | N | 0.39 | 0.125 | None | 1000 genomes | 3.19489E-03 | None | None | None | None | I | None | 1.21E-02 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| I/V | rs145204073 |
-1.487 | 0.041 | N | 0.39 | 0.125 | None | gnomAD-4.0.0 | 2.59231E-04 | None | None | None | None | I | None | 5.01454E-03 | 2.34114E-04 | None | 0 | 0 | None | 0 | 0 | 9.32798E-06 | 2.20022E-05 | 2.403E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.7328 | likely_pathogenic | 0.7398 | pathogenic | -2.142 | Highly Destabilizing | 0.207 | N | 0.536 | neutral | None | None | None | None | I |
| I/C | 0.8988 | likely_pathogenic | 0.8929 | pathogenic | -1.469 | Destabilizing | 0.981 | D | 0.625 | neutral | None | None | None | None | I |
| I/D | 0.9778 | likely_pathogenic | 0.9785 | pathogenic | -1.581 | Destabilizing | 0.932 | D | 0.703 | prob.neutral | None | None | None | None | I |
| I/E | 0.9604 | likely_pathogenic | 0.9582 | pathogenic | -1.466 | Destabilizing | 0.818 | D | 0.693 | prob.neutral | None | None | None | None | I |
| I/F | 0.3494 | ambiguous | 0.3623 | ambiguous | -1.346 | Destabilizing | 0.001 | N | 0.351 | neutral | N | 0.490074103 | None | None | I |
| I/G | 0.9449 | likely_pathogenic | 0.945 | pathogenic | -2.59 | Highly Destabilizing | 0.818 | D | 0.703 | prob.neutral | None | None | None | None | I |
| I/H | 0.9122 | likely_pathogenic | 0.9106 | pathogenic | -1.879 | Destabilizing | 0.981 | D | 0.659 | neutral | None | None | None | None | I |
| I/K | 0.8803 | likely_pathogenic | 0.8747 | pathogenic | -1.491 | Destabilizing | 0.818 | D | 0.701 | prob.neutral | None | None | None | None | I |
| I/L | 0.1009 | likely_benign | 0.0924 | benign | -0.917 | Destabilizing | None | N | 0.111 | neutral | N | 0.46631169 | None | None | I |
| I/M | 0.1848 | likely_benign | 0.1826 | benign | -0.829 | Destabilizing | 0.627 | D | 0.619 | neutral | N | 0.486124083 | None | None | I |
| I/N | 0.7999 | likely_pathogenic | 0.8135 | pathogenic | -1.482 | Destabilizing | 0.912 | D | 0.717 | prob.delet. | N | 0.518560385 | None | None | I |
| I/P | 0.8559 | likely_pathogenic | 0.873 | pathogenic | -1.298 | Destabilizing | 0.932 | D | 0.713 | prob.delet. | None | None | None | None | I |
| I/Q | 0.8995 | likely_pathogenic | 0.8928 | pathogenic | -1.502 | Destabilizing | 0.932 | D | 0.696 | prob.neutral | None | None | None | None | I |
| I/R | 0.8228 | likely_pathogenic | 0.8096 | pathogenic | -1.082 | Destabilizing | 0.818 | D | 0.714 | prob.delet. | None | None | None | None | I |
| I/S | 0.8092 | likely_pathogenic | 0.8264 | pathogenic | -2.235 | Highly Destabilizing | 0.492 | N | 0.63 | neutral | N | 0.488592845 | None | None | I |
| I/T | 0.7296 | likely_pathogenic | 0.7345 | pathogenic | -1.982 | Destabilizing | 0.324 | N | 0.597 | neutral | N | 0.500113735 | None | None | I |
| I/V | 0.0886 | likely_benign | 0.0877 | benign | -1.298 | Destabilizing | 0.041 | N | 0.39 | neutral | N | 0.486262214 | None | None | I |
| I/W | 0.9458 | likely_pathogenic | 0.9457 | pathogenic | -1.524 | Destabilizing | 0.981 | D | 0.651 | neutral | None | None | None | None | I |
| I/Y | 0.7966 | likely_pathogenic | 0.8114 | pathogenic | -1.271 | Destabilizing | 0.527 | D | 0.663 | neutral | 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.