Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16048 | 48367;48368;48369 | chr2:178616747;178616746;178616745 | chr2:179481474;179481473;179481472 |
| N2AB | 14407 | 43444;43445;43446 | chr2:178616747;178616746;178616745 | chr2:179481474;179481473;179481472 |
| N2A | 13480 | 40663;40664;40665 | chr2:178616747;178616746;178616745 | chr2:179481474;179481473;179481472 |
| N2B | 6983 | 21172;21173;21174 | chr2:178616747;178616746;178616745 | chr2:179481474;179481473;179481472 |
| Novex-1 | 7108 | 21547;21548;21549 | chr2:178616747;178616746;178616745 | chr2:179481474;179481473;179481472 |
| Novex-2 | 7175 | 21748;21749;21750 | chr2:178616747;178616746;178616745 | chr2:179481474;179481473;179481472 |
| 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/T | rs749678590  |
-2.589 | 1.0 | D | 0.746 | 0.53 | 0.676491819518 | gnomAD-2.1.1 | 1.97876E-04 | None | None | None | None | I | None | 0 | 1.33597E-03 | None | 0 | 0 | None | 0 | None | 0 | 0 | 4.99168E-04 |
| I/T | rs749678590 |
-2.589 | 1.0 | D | 0.746 | 0.53 | 0.676491819518 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 0 | 1.31251E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs749678590 |
-2.589 | 1.0 | D | 0.746 | 0.53 | 0.676491819518 | gnomAD-4.0.0 | 3.90696E-05 | None | None | None | None | I | None | 0 | 9.3486E-04 | None | 0 | 0 | None | 0 | 3.29489E-04 | 1.69611E-06 | 0 | 4.80815E-05 |
| I/V | None | None | 0.993 | N | 0.339 | 0.217 | 0.64836404711 | gnomAD-4.0.0 | 1.59377E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.77731E-05 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.9103 | likely_pathogenic | 0.9283 | pathogenic | -2.368 | Highly Destabilizing | 0.999 | D | 0.565 | neutral | None | None | None | None | I |
| I/C | 0.9566 | likely_pathogenic | 0.9631 | pathogenic | -1.698 | Destabilizing | 1.0 | D | 0.796 | deleterious | None | None | None | None | I |
| I/D | 0.9981 | likely_pathogenic | 0.9984 | pathogenic | -2.262 | Highly Destabilizing | 1.0 | D | 0.884 | deleterious | None | None | None | None | I |
| I/E | 0.9924 | likely_pathogenic | 0.9936 | pathogenic | -2.022 | Highly Destabilizing | 1.0 | D | 0.886 | deleterious | None | None | None | None | I |
| I/F | 0.5234 | ambiguous | 0.5378 | ambiguous | -1.378 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | N | 0.508348366 | None | None | I |
| I/G | 0.9898 | likely_pathogenic | 0.9903 | pathogenic | -2.93 | Highly Destabilizing | 1.0 | D | 0.869 | deleterious | None | None | None | None | I |
| I/H | 0.9915 | likely_pathogenic | 0.9931 | pathogenic | -2.261 | Highly Destabilizing | 1.0 | D | 0.875 | deleterious | None | None | None | None | I |
| I/K | 0.9738 | likely_pathogenic | 0.9803 | pathogenic | -1.761 | Destabilizing | 1.0 | D | 0.886 | deleterious | None | None | None | None | I |
| I/L | 0.3877 | ambiguous | 0.4214 | ambiguous | -0.749 | Destabilizing | 0.993 | D | 0.397 | neutral | N | 0.499481476 | None | None | I |
| I/M | 0.2621 | likely_benign | 0.2851 | benign | -0.733 | Destabilizing | 1.0 | D | 0.734 | prob.delet. | D | 0.634152996 | None | None | I |
| I/N | 0.9715 | likely_pathogenic | 0.9784 | pathogenic | -2.109 | Highly Destabilizing | 1.0 | D | 0.895 | deleterious | D | 0.635570909 | None | None | I |
| I/P | 0.9966 | likely_pathogenic | 0.9968 | pathogenic | -1.268 | Destabilizing | 1.0 | D | 0.894 | deleterious | None | None | None | None | I |
| I/Q | 0.9858 | likely_pathogenic | 0.9886 | pathogenic | -1.927 | Destabilizing | 1.0 | D | 0.886 | deleterious | None | None | None | None | I |
| I/R | 0.9628 | likely_pathogenic | 0.9698 | pathogenic | -1.572 | Destabilizing | 1.0 | D | 0.893 | deleterious | None | None | None | None | I |
| I/S | 0.9711 | likely_pathogenic | 0.9777 | pathogenic | -2.88 | Highly Destabilizing | 1.0 | D | 0.817 | deleterious | D | 0.592976272 | None | None | I |
| I/T | 0.8887 | likely_pathogenic | 0.9179 | pathogenic | -2.472 | Highly Destabilizing | 1.0 | D | 0.746 | deleterious | D | 0.536959657 | None | None | I |
| I/V | 0.1859 | likely_benign | 0.2017 | benign | -1.268 | Destabilizing | 0.993 | D | 0.339 | neutral | N | 0.495499325 | None | None | I |
| I/W | 0.9829 | likely_pathogenic | 0.9817 | pathogenic | -1.668 | Destabilizing | 1.0 | D | 0.861 | deleterious | None | None | None | None | I |
| I/Y | 0.9308 | likely_pathogenic | 0.942 | pathogenic | -1.374 | Destabilizing | 1.0 | D | 0.825 | 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.