Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27969 | 84130;84131;84132 | chr2:178562227;178562226;178562225 | chr2:179426954;179426953;179426952 |
| N2AB | 26328 | 79207;79208;79209 | chr2:178562227;178562226;178562225 | chr2:179426954;179426953;179426952 |
| N2A | 25401 | 76426;76427;76428 | chr2:178562227;178562226;178562225 | chr2:179426954;179426953;179426952 |
| N2B | 18904 | 56935;56936;56937 | chr2:178562227;178562226;178562225 | chr2:179426954;179426953;179426952 |
| Novex-1 | 19029 | 57310;57311;57312 | chr2:178562227;178562226;178562225 | chr2:179426954;179426953;179426952 |
| Novex-2 | 19096 | 57511;57512;57513 | chr2:178562227;178562226;178562225 | chr2:179426954;179426953;179426952 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/C | None | None | 0.988 | N | 0.564 | 0.363 | 0.506068822696 | gnomAD-4.0.0 | 1.36945E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.7995E-06 | 0 | 0 |
| F/L | rs1326312307  |
-0.007 | 0.003 | N | 0.27 | 0.228 | 0.166414681773 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.94E-06 | 0 |
| F/L | rs1326312307 |
-0.007 | 0.003 | N | 0.27 | 0.228 | 0.166414681773 | gnomAD-4.0.0 | 2.05427E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99798E-07 | 1.16214E-05 | 1.65848E-05 |
| F/S | None | None | 0.782 | N | 0.555 | 0.223 | 0.431602765429 | gnomAD-4.0.0 | 6.84724E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 1.87568E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.7228 | likely_pathogenic | 0.6656 | pathogenic | -1.185 | Destabilizing | 0.575 | D | 0.543 | neutral | None | None | None | None | I |
| F/C | 0.5444 | ambiguous | 0.4827 | ambiguous | -0.695 | Destabilizing | 0.988 | D | 0.564 | neutral | N | 0.483164438 | None | None | I |
| F/D | 0.8773 | likely_pathogenic | 0.842 | pathogenic | 0.159 | Stabilizing | 0.906 | D | 0.598 | neutral | None | None | None | None | I |
| F/E | 0.9122 | likely_pathogenic | 0.8894 | pathogenic | 0.178 | Stabilizing | 0.906 | D | 0.608 | neutral | None | None | None | None | I |
| F/G | 0.8095 | likely_pathogenic | 0.7756 | pathogenic | -1.39 | Destabilizing | 0.906 | D | 0.597 | neutral | None | None | None | None | I |
| F/H | 0.7198 | likely_pathogenic | 0.6613 | pathogenic | 0.116 | Stabilizing | 0.826 | D | 0.553 | neutral | None | None | None | None | I |
| F/I | 0.4014 | ambiguous | 0.3571 | ambiguous | -0.622 | Destabilizing | 0.338 | N | 0.551 | neutral | N | 0.469362143 | None | None | I |
| F/K | 0.9181 | likely_pathogenic | 0.9049 | pathogenic | -0.51 | Destabilizing | 0.826 | D | 0.605 | neutral | None | None | None | None | I |
| F/L | 0.904 | likely_pathogenic | 0.8844 | pathogenic | -0.622 | Destabilizing | 0.003 | N | 0.27 | neutral | N | 0.448554728 | None | None | I |
| F/M | 0.6783 | likely_pathogenic | 0.6442 | pathogenic | -0.724 | Destabilizing | 0.826 | D | 0.543 | neutral | None | None | None | None | I |
| F/N | 0.7817 | likely_pathogenic | 0.7403 | pathogenic | -0.636 | Destabilizing | 0.906 | D | 0.601 | neutral | None | None | None | None | I |
| F/P | 0.9721 | likely_pathogenic | 0.9685 | pathogenic | -0.796 | Destabilizing | 0.967 | D | 0.606 | neutral | None | None | None | None | I |
| F/Q | 0.8373 | likely_pathogenic | 0.8146 | pathogenic | -0.627 | Destabilizing | 0.906 | D | 0.606 | neutral | None | None | None | None | I |
| F/R | 0.8286 | likely_pathogenic | 0.8203 | pathogenic | -0.087 | Destabilizing | 0.906 | D | 0.601 | neutral | None | None | None | None | I |
| F/S | 0.5543 | ambiguous | 0.4868 | ambiguous | -1.235 | Destabilizing | 0.782 | D | 0.555 | neutral | N | 0.478045184 | None | None | I |
| F/T | 0.7177 | likely_pathogenic | 0.6631 | pathogenic | -1.124 | Destabilizing | 0.826 | D | 0.55 | neutral | None | None | None | None | I |
| F/V | 0.3852 | ambiguous | 0.345 | ambiguous | -0.796 | Destabilizing | 0.338 | N | 0.547 | neutral | N | 0.451764867 | None | None | I |
| F/W | 0.6289 | likely_pathogenic | 0.6264 | pathogenic | -0.274 | Destabilizing | 0.973 | D | 0.556 | neutral | None | None | None | None | I |
| F/Y | 0.2122 | likely_benign | 0.1888 | benign | -0.373 | Destabilizing | 0.001 | N | 0.299 | neutral | N | 0.47113657 | 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.