Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27791 | 83596;83597;83598 | chr2:178562761;178562760;178562759 | chr2:179427488;179427487;179427486 |
| N2AB | 26150 | 78673;78674;78675 | chr2:178562761;178562760;178562759 | chr2:179427488;179427487;179427486 |
| N2A | 25223 | 75892;75893;75894 | chr2:178562761;178562760;178562759 | chr2:179427488;179427487;179427486 |
| N2B | 18726 | 56401;56402;56403 | chr2:178562761;178562760;178562759 | chr2:179427488;179427487;179427486 |
| Novex-1 | 18851 | 56776;56777;56778 | chr2:178562761;178562760;178562759 | chr2:179427488;179427487;179427486 |
| Novex-2 | 18918 | 56977;56978;56979 | chr2:178562761;178562760;178562759 | chr2:179427488;179427487;179427486 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/F | rs755033702  |
-0.488 | 0.995 | N | 0.519 | 0.243 | 0.518421792786 | gnomAD-2.1.1 | 1.79E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 6.54E-05 | None | 0 | 2.35E-05 | 0 |
| L/F | rs755033702 |
-0.488 | 0.995 | N | 0.519 | 0.243 | 0.518421792786 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| L/F | rs755033702 |
-0.488 | 0.995 | N | 0.519 | 0.243 | 0.518421792786 | gnomAD-4.0.0 | 5.57968E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.23907E-06 | 2.19679E-05 | 3.20482E-05 |
| L/I | None | None | 0.57 | N | 0.503 | 0.162 | 0.384252928164 | gnomAD-4.0.0 | 1.36905E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99698E-07 | 0 | 1.65804E-05 |
| L/P | None | None | 0.998 | N | 0.661 | 0.522 | 0.629359936291 | gnomAD-4.0.0 | 4.78062E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 7.24638E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.1601 | likely_benign | 0.184 | benign | -0.595 | Destabilizing | 0.936 | D | 0.517 | neutral | None | None | None | None | I |
| L/C | 0.5454 | ambiguous | 0.5942 | pathogenic | -0.741 | Destabilizing | 1.0 | D | 0.542 | neutral | None | None | None | None | I |
| L/D | 0.5912 | likely_pathogenic | 0.6204 | pathogenic | -0.071 | Destabilizing | 0.99 | D | 0.667 | neutral | None | None | None | None | I |
| L/E | 0.3179 | likely_benign | 0.334 | benign | -0.15 | Destabilizing | 0.916 | D | 0.56 | neutral | None | None | None | None | I |
| L/F | 0.1846 | likely_benign | 0.2078 | benign | -0.544 | Destabilizing | 0.995 | D | 0.519 | neutral | N | 0.519788311 | None | None | I |
| L/G | 0.453 | ambiguous | 0.4902 | ambiguous | -0.757 | Destabilizing | 0.99 | D | 0.545 | neutral | None | None | None | None | I |
| L/H | 0.2835 | likely_benign | 0.3028 | benign | 0.021 | Stabilizing | 0.996 | D | 0.647 | neutral | N | 0.472685458 | None | None | I |
| L/I | 0.0835 | likely_benign | 0.0878 | benign | -0.29 | Destabilizing | 0.57 | D | 0.503 | neutral | N | 0.478096404 | None | None | I |
| L/K | 0.3059 | likely_benign | 0.3182 | benign | -0.36 | Destabilizing | 0.603 | D | 0.501 | neutral | None | None | None | None | I |
| L/M | 0.1057 | likely_benign | 0.1142 | benign | -0.467 | Destabilizing | 0.987 | D | 0.523 | neutral | None | None | None | None | I |
| L/N | 0.3017 | likely_benign | 0.3162 | benign | -0.234 | Destabilizing | 0.99 | D | 0.668 | neutral | None | None | None | None | I |
| L/P | 0.3694 | ambiguous | 0.3779 | ambiguous | -0.359 | Destabilizing | 0.998 | D | 0.661 | neutral | N | 0.517574725 | None | None | I |
| L/Q | 0.1499 | likely_benign | 0.1635 | benign | -0.419 | Destabilizing | 0.524 | D | 0.44 | neutral | None | None | None | None | I |
| L/R | 0.2819 | likely_benign | 0.3053 | benign | 0.168 | Stabilizing | 0.969 | D | 0.618 | neutral | N | 0.503568064 | None | None | I |
| L/S | 0.2117 | likely_benign | 0.2465 | benign | -0.703 | Destabilizing | 0.726 | D | 0.368 | neutral | None | None | None | None | I |
| L/T | 0.1806 | likely_benign | 0.2069 | benign | -0.671 | Destabilizing | 0.898 | D | 0.487 | neutral | None | None | None | None | I |
| L/V | 0.0801 | likely_benign | 0.087 | benign | -0.359 | Destabilizing | 0.636 | D | 0.524 | neutral | N | 0.469764922 | None | None | I |
| L/W | 0.4049 | ambiguous | 0.4422 | ambiguous | -0.557 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | I |
| L/Y | 0.3852 | ambiguous | 0.4112 | ambiguous | -0.32 | Destabilizing | 0.967 | D | 0.527 | 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.