Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15956 | 48091;48092;48093 | chr2:178617129;178617128;178617127 | chr2:179481856;179481855;179481854 |
| N2AB | 14315 | 43168;43169;43170 | chr2:178617129;178617128;178617127 | chr2:179481856;179481855;179481854 |
| N2A | 13388 | 40387;40388;40389 | chr2:178617129;178617128;178617127 | chr2:179481856;179481855;179481854 |
| N2B | 6891 | 20896;20897;20898 | chr2:178617129;178617128;178617127 | chr2:179481856;179481855;179481854 |
| Novex-1 | 7016 | 21271;21272;21273 | chr2:178617129;178617128;178617127 | chr2:179481856;179481855;179481854 |
| Novex-2 | 7083 | 21472;21473;21474 | chr2:178617129;178617128;178617127 | chr2:179481856;179481855;179481854 |
| 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/E | None | None | 0.999 | N | 0.448 | 0.158 | 0.269111216191 | gnomAD-4.0.0 | 6.85765E-07 | None | None | None | None | N | None | 0 | 2.25398E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/N | rs372881122  |
0.715 | 1.0 | D | 0.783 | 0.38 | None | gnomAD-2.1.1 | 2.54E-05 | None | None | None | None | N | None | 2.08995E-04 | 0 | None | 0 | 0 | None | 3.31E-05 | None | 0 | 7.96E-06 | 0 |
| D/N | rs372881122 |
0.715 | 1.0 | D | 0.783 | 0.38 | None | gnomAD-3.1.2 | 5.93E-05 | None | None | None | None | N | None | 1.69115E-04 | 0 | 0 | 0 | 1.94932E-04 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/N | rs372881122 |
0.715 | 1.0 | D | 0.783 | 0.38 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| D/N | rs372881122 |
0.715 | 1.0 | D | 0.783 | 0.38 | None | gnomAD-4.0.0 | 1.55286E-05 | None | None | None | None | N | None | 1.73722E-04 | 0 | None | 0 | 2.25104E-05 | None | 1.56558E-05 | 0 | 6.79117E-06 | 1.10512E-05 | 1.60545E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.4085 | ambiguous | 0.4274 | ambiguous | -0.113 | Destabilizing | 1.0 | D | 0.725 | deleterious | N | 0.491630238 | None | None | N |
| D/C | 0.8485 | likely_pathogenic | 0.8704 | pathogenic | 0.374 | Stabilizing | 1.0 | D | 0.829 | deleterious | None | None | None | None | N |
| D/E | 0.3493 | ambiguous | 0.3571 | ambiguous | -0.252 | Destabilizing | 0.999 | D | 0.448 | neutral | N | 0.504344444 | None | None | N |
| D/F | 0.8669 | likely_pathogenic | 0.8791 | pathogenic | -0.421 | Destabilizing | 1.0 | D | 0.8 | deleterious | None | None | None | None | N |
| D/G | 0.4662 | ambiguous | 0.4845 | ambiguous | -0.25 | Destabilizing | 1.0 | D | 0.787 | deleterious | D | 0.580418752 | None | None | N |
| D/H | 0.6007 | likely_pathogenic | 0.6371 | pathogenic | -0.324 | Destabilizing | 1.0 | D | 0.886 | deleterious | D | 0.608846651 | None | None | N |
| D/I | 0.6854 | likely_pathogenic | 0.7215 | pathogenic | 0.179 | Stabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | N |
| D/K | 0.6357 | likely_pathogenic | 0.6638 | pathogenic | 0.505 | Stabilizing | 1.0 | D | 0.838 | deleterious | None | None | None | None | N |
| D/L | 0.7025 | likely_pathogenic | 0.7252 | pathogenic | 0.179 | Stabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | N |
| D/M | 0.8772 | likely_pathogenic | 0.8876 | pathogenic | 0.431 | Stabilizing | 1.0 | D | 0.803 | deleterious | None | None | None | None | N |
| D/N | 0.1827 | likely_benign | 0.1809 | benign | 0.441 | Stabilizing | 1.0 | D | 0.783 | deleterious | D | 0.564290984 | None | None | N |
| D/P | 0.8178 | likely_pathogenic | 0.8284 | pathogenic | 0.102 | Stabilizing | 1.0 | D | 0.823 | deleterious | None | None | None | None | N |
| D/Q | 0.7046 | likely_pathogenic | 0.7264 | pathogenic | 0.416 | Stabilizing | 1.0 | D | 0.83 | deleterious | None | None | None | None | N |
| D/R | 0.7076 | likely_pathogenic | 0.7374 | pathogenic | 0.488 | Stabilizing | 1.0 | D | 0.81 | deleterious | None | None | None | None | N |
| D/S | 0.301 | likely_benign | 0.3025 | benign | 0.331 | Stabilizing | 1.0 | D | 0.792 | deleterious | None | None | None | None | N |
| D/T | 0.519 | ambiguous | 0.5278 | ambiguous | 0.428 | Stabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | N |
| D/V | 0.4777 | ambiguous | 0.5127 | ambiguous | 0.102 | Stabilizing | 1.0 | D | 0.761 | deleterious | D | 0.648871225 | None | None | N |
| D/W | 0.967 | likely_pathogenic | 0.9741 | pathogenic | -0.419 | Destabilizing | 1.0 | D | 0.772 | deleterious | None | None | None | None | N |
| D/Y | 0.4791 | ambiguous | 0.5248 | ambiguous | -0.211 | Destabilizing | 1.0 | D | 0.8 | deleterious | D | 0.649991654 | 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.